Dr. Bob Sears is best known for his 2007 work, The Vaccine Book, ostensibly written “to give parents a balanced look at pros and cons of vaccination so that they can make an educated decision.” In reality, the book has only added to the unnecessary fear, uncertainty and doubt about vaccines that have driven thousands of parents to leave their children vulnerable to preventable diseases. And while America’s medical establishment has caught on to Sears, he still enjoys a following. His book has sold about 50,000 copies, and Sear’s Facebook page lists over 6,000 followers.
Last week Sears told his FB followers that we can only truly know that vaccines are safer than the diseases they protect us from if the CDC studies health outcomes of vaccinated and unvaccinated children. Sears no doubt includes autism in those “health outcomes”, since he has advised parents to avoid vaccinating their autistic children until they are “recovered” from the disorder. Anti-vaccine activists have been agitating for such a study for years, most recently at the shameful Congressional anti-vaccine hearing last November 29. Jenny McCarthy’s Generation Rescue even attempted such a survey by telephone in 2007. It found that autism was more common among unvaccinated children than vaccinated.
Epidemiologists tell us such a study, done well, would be unethical, since it would mean leaving many thousands of children vulnerable to disease, just to prove what medical science already knows – that vaccines don’t cause autism. Sears says there are enough totally unvaccinated children around to conduct such a study, and on Facebook he cited a paper that supposedly shows that 5-10 percent of American children have never been vaccinated.
The IOM and the CDC continue to hide behind the claim that to do a comparative study of unvaccinated versus vaccinated children would be unethical. But as long as they neglect to do this research, many parents will continue to decline vaccines over the concern about lack of safety research.
The IOM states that one challenge of an unvaccinated study is that there is an inadequate number of study subjects, as less than 1% of children are completely unvaccinated. I don’t agree with this statistic. It’s more like 5%, and could even be 10%. One brand new international study revealed that 10% of households surveyed had children who were completely unvaccinated. 10%!!! And it was the more educated and wealthier families that were more likely to be unvaccinated. The IOM’s claim that there aren’t enough unvaccinated children to study simply isn’t true. With over 4 million babies being born in the U.S. every year, they would have their pick of about 400,000 unvaccinated children to study each year.
Sears links to a meta-analysis of vaccine surveys published last summer in the journal Tropical Medicine and International Health. Xavier Bosch-Capblanch from the University of Basel, Switzerland, and his team reviewed 241 nationally representative household vaccination surveys in 96 low and medium income countries. The percentage of unvaccinated children (ages 12-59 months) was 9.9% across all surveys, but ranged from zero percent (Albania,Peru, and Uzbekistan) to 28.5% (Ethiopia). Sears’s claim that ten percent of American children are completely unvaccinated puts the country on par with Namibia (9.2% in 2007), Haiti (10.3% in 2006), and Yemen (10.9% in 2006). It also means that scores of developing countries, including Vietnam (1%) Tajikistan (.9%), and Sierra Leone (1.9%), should think twice before issuing visas for American children.
If Sears was truly serious about helping parents make an educated decision, he could have cited Allison Kennedy, a CDC epidemiologist, who surveyed parents to examine intentions, behaviors and concerns about vaccines. In Confidence about vaccines in the United States: Understanding Patient Perceptions (2011), her team found about two percent of US children aged six or younger were totally unvaccinated. Those numbers are in line with Smith et.al. (2004), which reported a minuscule .3% unvaccinated of children 19-35 months old. The CDC’s 2010 National Immunization Survey found that 1 percent of toddlers were completely unvaccinated.
Despite Sears’s best efforts, the percent of fully vaccinated children has increased over the past decade. That’s discouraging news for Sears and others who have doubled down on a vaxed v. unvaxed study. But overall rates should not mask the real harm of anti-vaccine propaganda – encouraging community clusters of vaccine rejectionism that have led to unnecessary suffering. One such cluster incubated a measles outbreak in San Diego in 2008. The index patient was a boy who had just returned from a trip to Switzerland. By the time the virus was contained, four others came down with a disease that can lead to pneumonia, encephalitis, and even death. His family’s pediatrician? Dr. Bob Sears.
What kind of doctor, you might ask, would encourage parents to withhold an important vaccine? The kind who aligns himself with the worst elements of the antivaccine movement. The kind who misrepresents published science so as to fuel the anti-vaccine movement’s push for an unethical study. The kind to fabricate his own, untested vaccine schedule, then package it in The Vaccine Book.
—
By Autism News Beat
Left Brain Right Brain 
When I was reading this it was like wow, can Sullivan get any dumber? Only to find out it was Autismnewsbeatmeoff. That explains it.
Joe,
I count over 10 pseudonyms for you on this site. Most as useless as the one above.
@joeddd
sockpuppetry, a sign that an individual has no rational argument and is therefore reduced to posting in order to make him/her/itself look even partially revelant.
Congrats on proving that you have no rational argument.
It seems to me that the research Dr. Bob is suggesting won’t really prove anything. (Even if there is a correlation, it won’t be proof, since the study cannot be double-blind, by definition.)
Why not have research focus on children who have adverse reactions, and study them in detail in a controlled environment to find out what is causing the reaction?
If the reaction is similar to an allergy, then it should be fairly easy to document and treat. If it is an immune system “overload”, as some people claim, that should be easy to diagnose as well.
We know for a fact that millions of kids get vaccinated with no problems. I am more interested in the few who do have problems. Are the problems verifiable? Are they treatable? Are they preventable?
I have not read Sear’s book, so maybe I am off base, but why not recommend research into medical details, rather than yet another series of epidemiological studies?
The allergy concerns are noted, and there are notes on contraindications for those children with specific allergies. The problem with ‘immune system “overload”’ is that you must actually define it and its symptoms. You cannot go by what “some people claim”, since they all seem to have different stories. You need consistency in order to actually define a problem.
“Are the problems verifiable?”
Which is exactly the purpose of the Vaccine Adverse Event Reporting System and the Vaccine Safety Datalink Program. This is how the issue with RotaShield was discovered.
futuredave5: I worked as a public health nurse/clinician-epidemiologist at a large suburban County health department (population 1.2 million). During my tenure there, I vaccinated thousands of children and my colleague doctors and nurses collectively, administered hundreds of thousands of vaccinations to children during our tenures at the health department. No serious adverse event was ever reported to a private physician or to the CDC, and in turn reported to us.
When we administered any vaccine we always had an ampule of epinephrine and syringes nearby to administer to anyone who had an immediate reaction (anaphylaxis) to a vaccine; none of us ever had to administer the epinephrine. We knew the hundreds of pediatricians and family practice doctors who vaccinated their young patients and none of them ever had to administer epinephrine for an anaphylactic reaction to a vaccine.
You have questions about vaccines triggering an “immune response” and “overwhelming the immune system”. Here’s an excellent website (Children’s Hospital of Philadelphia), which will provide you with information about vaccine safety.
http://www.chop.edu/service/vaccine-education-center/vaccine-safety/
Lilady: Thanks for the response. This literature is more on my level. The discussion between Matt and pDrone goes a little over my head.
The reaction my son had to various vaccines was never so severe that we rushed him back to the hospital, so I doubt people like us would show up in any databases. Even the HepB reaction, technically, was never linked to the vaccine by anyone but me, and all I have is subjective.
We are now considering vaccine boosters in any case where my son’s immune system does not demonstrate adequate immunity. When I look to research the reactions, though, the literature usually talks about how rare anaphylaxis is. Honestly, I think my son had some reactions that were more adverse than typical, but less severe than anaphylaxis.
I also read a lot about Anti-nuclear Antibodies, and I am not even sure how that enters into the discussion. If autistic kids test higher than the general population for ANA, then what are the implications for vaccines?
futuredave5: I hope you don’t mind me posting above you.
I’d like to answer some of your questions, but I would need to know what age your son is to see if your child is due for any booster shots.
I’m also wondering why your child’s doctor is contemplating an ANA test, i.e., is your son symptomatic for an auto immune disorder? ANA testing is usually not done alone, it is often combine with an ESR (Erythrocyte Sedimentation Rate), CRP (C-Reactive Proteins) and/or RF (Rheumatoid Factor). ANA tests sometimes yield false positive test results.
Here’s a website that explains what an ANA test is:
http://labtestsonline.org/understanding/analytes/ana/tab/faq
I have no idea why an autistic child would have a positive ANA test result…in the absence of symptoms of an auto-immune disease/disorder. On what website did you see this testing of autistic children for positive results?
Lilady: The ANA test was run when my son was about 4. We were trying to determine what vaccines my son really needed, and trying to determine what we should do about the adverse reactions.
The adverse reactions included fever, rash, and screaming as if he was in pain. Also, he was very tired, but had trouble sleeping.
The doctor said that high ANA tests were more common in autistic children than in the general population, and did not appear to mean much of anything. He said that some symptoms of autism are similar to an autoimmune problem, and that an ANA test was one step in figuring out if that applied to my son.
At any rate, we did titer tests at the same time, and the doctor determined from the titer tests that we could delay the vaccine schedule with little or no risk. He seemed to imply that the ANA test was just something he wanted to have in case the titer tests did not answer his questions.
When I research it on the web, of course, it is hard for me to separate the real science from the unproven theories. This is why I mentioned it in relation to this article. It seems to me that every child is so different that epidemiological studies are not likely to spot conditions that only hold true for a small minority.
Even if Dr. Bob gets his study, I suspect it will prove the opposite of what he implies. I suspect that the vast majority of un-vaccinated children are at risk from common diseases, and that this risk will easily outweigh the risks of vaccination in the general population.
In short, I don’t think we need another study on the effects of vaccination in the general population. That issue appears to be settled. I would rather see a study of the effect of vaccination on children already known to be autistic.
Alternately, how about a study of the effect of the second vaccination on children who reported high fever after their first? Or, how about a study of the effect of vaccination on children who have a positive ANA test?
I didn’t mean to imply that I was freaking out about the ANA test results. I just wish it was more useful.
Hi futuredave5 –
I’ve seen several of your posts here and thought I’d let you know that I appreciate your thoughtful approach. Of course, coming from me, that is a sort of kiss of death for a lot of the regulars here, so take that with a grain of salt.
If it is an immune system “overload”, as some people claim, that should be easy to diagnose as well.
I’ve thought about this particular statement quite a bit; I think that overload is a bad term, it doesn’t really mean anything empirical, and is often used by ‘skeptics’ as a way to bash people who may have concerns about vaccination. By way of example, lilady’s link from CHOP on the question of ‘overwhelming’ the immune system goes on to expound on ” the theoretical capacity determined by the genes that make different antibodies would allow for as many as 109-1011″, as if when you thought ‘overload’, you were curious as to the theoretical limit of molecular configurations our B cells could memorize, and somehow overcoming that limit.
No parent, in the history of the world, ever, has substituted the word ‘overload’ for ‘exceed my infants b-cell capacities to generate immunologically distinct regions of viruses and bacteria.’
I think the more interesting way to phrase the question might be, ‘can vaccination modify the immune system in ways other than generation of immunological memory?’ I don’t know the answer to that question, but I do know that back of the cocktail napkin calculations on B-cell configuration capacities isn’t the right way to come to an answer. I also know that animal models tell us with consistency that immune challenges in early life have the capacity to persistently modify immune function throughout the lifespan. Our existing suite of research into vaccination is, unfortunately, not appropriately designed to understand if this is happening to our infants.
I have not read Sear’s book, so maybe I am off base, but why not recommend research into medical details, rather than yet another series of epidemiological studies?
This is exactly, exactly correct. The epidemiology is so damned messy right now that any value would be meaningless, and our understanding of some of the medical details is only barely better.
“No parent, in the history of the world, ever, has substituted the word ‘overload’ for ‘exceed my infants b-cell capacities to generate immunologically distinct regions of viruses and bacteria.’ ”
Paul Offit is a parent.
Moving away from that obvious pedantic statement– “…but I do know that back of the cocktail napkin calculations on B-cell configuration capacities isn’t the right way to come to an answer”
Please, educate us. If you know tht isn’t the correct method, why? Show your work.
Hi Sullivan –
Please, educate us. If you know that isn’t the correct method, why? Show your work.
I’m a little bit confused as to why you are so terse with me, but OK.
The short answer to ‘why’ is: Because it is so crazy easy to illustrate that it is a gross over simplification of the immune system. Do you honestly think that we can or should use a single measurement point, theoretical conformational patterns on B cells, as a metric to reach any conclusions about something as complicated and intertwined as the immune system? Why?
Has it occurred to you (or Dr. Offit?) that there are components to the immune system other than B-Cells?
Have you wondered why people have spent entire careers trying to understand the time dependencies of the developing immune system, or the distinct categories of toll like receptors that initiate the immune response based on classification of pathogen in relation to vaccines, if B cell capacities were the only metric of interest? Has it occurred to you to wonder if maybe, just maybe, there might be a difference in the qualitative nature of the innate immune response when identifying a single snipet of a bacteria versus the entire thing? How can understanding the theoretical capacity of B-cells to conform to molecular shapes tell us anything about the qualitative differences between a naturally occuring pathogen (i.e., a bacteria) or an adjuvant? If counting B-cell slots ‘used’ by vaccination is our only metric of interest in understanding the influence of vaccines, what should we make of the fact that the DTAP vaccine, with only 5 antigens, has a greater frequency of fever than the chicken pox vaccine, with 69 antigens? If I didn’t have Dr. Offit to explain things to me, I might start to think B cell capacity is not a sufficiently broad data pattern to understand the depth of the immune system.
There is absolutely no scientifically defendable reason to try to aggregate the sum of potential vaccine interactions down to B-cell capacities. It is a whitewash, and an amateurish one at most charitable. Dr. Offit knows full well that the question of ‘overriding the immune system’ is a question born of naivety and, indeed, ignorance of the immune system, and instead of giving a nuanced answer regarding the complexity of the system and the problems with answering such an open question, instead he chose a childish caricature answer to a dumb question asked by people who don’t understand they’re being taken for a ride.
While Dr. Offit is technically a parent (I guess?), the article was not written to address Dr. Offit’s concerns, but rather, everyday ordinary people, non scientists, people that don’t have the first clue what a B-cell, or an epitope is.
The longer view would be that the ‘right’ answer to the question of ‘do vaccines overload the immune system’ is: “‘Overloading’ the immune system is insufficiently defined to arrive at meaningful conclusions.” The right answer isn’t to pick a single metric out of hundreds or thousands that are available, throw a calculator and a handful of deeply esoteric immunology keywords into a blender and push the ‘results’ back out.
But I’ll show you what I mean from the literature.
Modulation of the infant immune responses by the first pertussis vaccine administrations
Many efforts are currently made to prepare combined vaccines against most infectious pathogens, that may be administered early in life to protect infants against infectious diseases as early as possible. However, little is known about the general immune modulation induced by early vaccination. Here, we have analyzed the cytokine secretion profiles of two groups of 6-month-old infants having received as primary immunization either a whole-cell (Pw) or an acellular (Pa) pertussis vaccine in a tetravalent formulation of pertussis-tetanus-diphtheria-poliomyelitis vaccines. Both groups of infants secreted IFN-gamma in response to the Bordetella pertussis antigens filamentous haemagglutinin and pertussis toxin, and this response was correlated with antigen-specific IL-12p70 secretion, indicating that both pertussis vaccines induced Th1 cytokines. However, Pa recipients also developed a strong Th2-type cytokine response to the B. pertussis antigens, as noted previously. In addition, they induced Th2-type cytokines to the co-administrated antigen tetanus toxoïd, as well as to the food antigen beta-lactoglobulin. Furthermore, the general cytokine profile of the Pa recipients was strongly Th2-skewed at 6 months, as indicated by the cytokines induced by the mitogen phytohaemagglutinin. These data demonstrate that the cytokine profile of 6-month-old infants is influenced by the type of formulation of the pertussis vaccine they received at 2, 3 and 4 months of life. Large prospective studies would be warranted to evaluate the possible long-term consequences of this early modulation of the cytokine responses in infants.
Now, you’ll notice that no where in this paper is there any mention of the B-cell immunological capacity. But what the authors did find is that they could tell by blood cytokine profile, if a child got the DTP or DTAP. They observed a baseline line change in an array of cytokines between the two groups; indeed, a ‘modulation of the infant immune response’. Now, while these children did not, apparently, show signs of an ‘overwhelmed’ immune system, they did show evidence of a changed immune system.
Why would anyone bother to perform this type of measurement if B-cell configuration values are the best way to understand if vaccination changed the immune system? Why bother to try to quantify the cytokine profile as TH1 polarized in one group? Why didn’ the editors of Vaccine reject this paper, as it ignored our one true measurement of immune modulation, how many potential combinations of conformational patterns our B-cells could hold post vaccination?
I wonder how, on Earth calculating B-cell capacities is able to take into consideration time dependent changes in innate immune response in infants?
Multiplex analysis of toll-like receptor-stimulated neonatal cytokine response
Cord blood production of regulatory Th1 and Th2 cytokines following TLR stimulation is decreased compared to that of adult blood. In contrast, TLR-stimulated proinflammatory cytokine production was markedly higher in neonates than in adults, with the exception of TLR-4-induced TNF-alpha production. The human neonate’s increased susceptibility to bacterial infections may be related to abnormal TLR responsiveness, with enhanced proinflammatory and decreased regulatory cytokine production.
Check that out; regulatory biomarkers are decreased in newborns compared to adults, and inflammatory cytokine profiles are increased (in most instances). This isn’t a study about vaccination per se; but it should serve to inform us on the complexity of the system that we are trying to understand on the basis of an insufficient parameter (‘overloaded’), and insufficient answer (B-cell capacity). You might also wonder why we would bother with cord blood if we understood the cytokine response following vaccination? We *should* be able to cull out TLR4/TLR2/TLR# profiles based on post vaccination, in vivo measurments; except, we don’t have any of that data. It hasn’t been studied. This is one reason Dr. Offit had to resort to B-cell multiplication antics.
So, just as a fun little thought experiment; consider we have evidence that
1) Newborns have decreased regulatory capacities compared to adults.
2) Newborns have increased inflammatory production compared to adults (for many measurements/ TLR4\TNF-Alpha, apparently excluded).
3) Children with autism have been shown to create more inflammatory cytokines, and reduced regulatory cytokines compared to controls. They also have a distinctive neuroimmune environment consistent with chronically activated microglia and neuroanatomy consistent with alterations in synpatic pruning (among other things). [tons of references linkable upon request]
4) Vaccines trigger the innate immune system; they don’t work without doing so.
5) When we trigger the innate immune system outside of the CNS, we also trigger the microglia inside the CNS. [Microglial activation and TNFalpha production mediate altered CNS excitability following peripheral inflammation]
6) The microglia are supposed to be kind of busy in infancy, what with all of the synaptic pruning, and ongoing proliferation and colonization of the brain going on.
So, if the question was asked, instead, was ‘what evidence do we have that triggering the innate immune system during infancy does not alter neurodevelopment through pertubations of microglial activity?’, the answer is not, ‘B cells have large memory banks.’ Unfortunately, the answer to that question is not available in the literature, because we haven’t been clever enough until very recently to even know that might be something worth looking at, much less having gotten around to trying to design an experiment to perform a test.
What if we had animal models that told us, again and again, that early life is a timeframe wherein wherein the immune system, up to and including the neuroimmune system, is maleable to insults in such a way that a change may be persistent, but that same insult, later in life, does not have the same effect? What if those effects included the persistence of chronically activated microglia, changes in seizure susceptibility, alterations in HPA-Axis metabolism, and ultimately, behaviors. How would calculating B-cell capacities help us understand if any of these findings from the animal realm had parallels to vaccination of human infants?
All of those findings from the animal realm postdate our additions to the vaccine schedule by nearly a decade, or more, and are completely invisible to a study methodology that comprises our existing knowledge set. If you’d like I can look up the references for those categories above and link them. None of them, and I mean none, are discuss B-cell capacity as a potential mechanism of action.
B cell capacity is a number riddled load of horse-hockey; it is a dodge designed to give a sciency sounding answer, nothing more.
That’s my work.
– pD
“I’m a little bit confused as to why you are so terse with me, but OK. ”
Busy. And we’ve had enough exchanges that I figured you would roll with it.
“While Dr. Offit is technically a parent (I guess?),”
“Technically a parent”? Oh-kay. I don’t know what “technically” a parent is as opposed to just being a parent. It’s not like he was a sperm donor who never saw his offspring.
“Has it occurred to you (or Dr. Offit?) that there are components to the immune system other than B-Cells? ”
For me, yes. And for Dr. Offit, considering his work and his profession, yes. And, you avoided the point that there is a clear and obvious example that a parent has considered the calculation you derided.
“Because it is so crazy easy to illustrate that it is a gross over simplification of the immune system.”
I don’t see where he’s suggesting that B-cells are the entirety of the immune system. At this point I have to ask when the last time you looked at the paper in question was? Seriously–here’s the link besides going into detail about various aspects of the immune system, he begins the section where he makes his calculation thus:
He hasn’t assumed that B cells are the entirety of the immune system, he assumes that they are the limiting factor in responding to vaccine antigens.
“The right answer isn’t to pick a single metric out of hundreds or thousands that are available, throw a calculator and a handful of deeply esoteric immunology keywords into a blender and push the ‘results’ back out. ”
So you throw out the calculator, but move right in to throwing deeply esoteric immunology kewords into a blender. This is progress?
“we also trigger the microglia inside the CNS.”
As opposed to triggering them outside the CNS?!?
“Children with autism have been shown to create more inflammatory cytokines, and reduced regulatory cytokines compared to controls. They also have a distinctive neuroimmune environment consistent with chronically activated microglia and neuroanatomy consistent with alterations in synpatic pruning (among other things). [tons of references linkable upon request]”
I’m sure you can come up with tons of citations. Can you come up with what they mean in this regard? If so, write it up and submit it. At this point one can’t say if the microglia are activated because they themselves are somehow different in autistics or if there is an underlying cause that they are reacting to.
“So, just as a fun little thought experiment; consider we have evidence that”
I see what Prometheus calls a “string of pearls”. You haven’t logically connected the various points to draw a conclusion.
“1) Newborns have decreased regulatory capacities compared to adults.”
I don’t know what you mean by “regulatory capacity” but as far as reduced immune response, covered in Dr. Offit’s paper. Did you miss that section?
“3) Children with autism have been shown to create more inflammatory cytokines, and reduced regulatory cytokines compared to controls. ”
Except when they have lower levels–http://www.ncbi.nlm.nih.gov/pubmed/22917523
“4) Vaccines trigger the innate immune system; they don’t work without doing so.”
This will come as news to Dr. Offit, don’t you think? (yes, that’s sarcasm)
“5) When we trigger the innate immune system outside of the CNS, we also trigger the microglia inside the CNS. [Microglial activation and TNFalpha production mediate altered CNS excitability following peripheral inflammation http://www.ncbi.nlm.nih.gov/pubmed/18955701 ]”
Are microglia activated for every trigger of the innate immune system? You seem to be implying so. They induced gut inflammation using a chemical and found brain inflammation in rats. Also, does this induce chronic inflammation? Or is chronic inflammation worsened by this? Is it the same type of activation or in the same region of the brain. The authors write “We observed increased microglial activation and number in the hippocampus and adjacent EC in animals with peripheral inflammation.” Vargas (and others) have pointed to the cerebral cortex and other regions.
How about triggering the adaptive immune system. We are talking about vaccines, right? Why did you move away from the topic?
Your point sounds interesting up until the point where one realizes that there are so many open questions as to render the statement nearly useless.
“B cell capacity is a number riddled load of horse-hockey; it is a dodge designed to give a sciency sounding answer, nothing more. ”
I will refrain from statements about “sciency sounding answers” being “horse-hocky” at this point.
pD–
sorry for the choppy response (no pun intended)
Could I draw your attention to this paragraph from Dr. Offit’s paper:
It seems to address immediately some of your points–the fact that the immune system is more than B-cells, that children have a different response than adults and why he focused on B-cells for his calculation.
Hi Sullivan –
@Ugh re: comment formatting.
He hasn’t assumed that B cells are the entirety of the immune system, he assumes that they are the limiting factor in responding to vaccine antigens.
Sure, but there is no reason to believe that this assumption, that a ‘limiting factor in responding to vaccine antigens’ is a reasonable answer to a question as vague as ‘do vaccines overwhelm the immune system?’
Did the DTP/DTAP study I linked to give you some hint of why that might be an incomplete answer to such a complicated system?
So you throw out the calculator, but move right in to throwing deeply esoteric immunology kewords into a blender.
I am not writing an article designed for parents who know nothing about immunology who are worried about vaccinations. In order to illustrate the complexity of a system, a system that cannot be adequately described through multiplication, the details are necessary.
As opposed to triggering them outside the CNS?!?
I’m not sure I know what you mean here. Perhaps I was unclear; my point being that it is a relatively new piece of information that an immune response initiated outside the CNS also winds up activating the microglia inside the CNS. The link I provided is from 2008. Perhaps you were already aware of this.
There have been a few subsequent studies, but this mechanisms by which this happens are still largely mysterious to us. For another nice example, you might take a look at A broad upregulation of cerebral chemokine genes by peripherally-generated inflammatory mediators I figure there are enough keywords in the title to get you going; it’s a pretty neat study and eventually they wound up transferring blood to naive animals and observing upregulated immune responses in the CNS.
At this point one can’t say if the microglia are activated because they themselves are somehow different in autistics or if there is an underlying cause that they are reacting to
We are in agreement. However, while there are many possible ways we can arrive at this end state, the animal models do tell us that one way that is biologically plausible, and indeed, reproducible, is through early life immune challenge; that is why it is salient towards a discussion on vaccination, which is, in essence, an early life immune challenge. I am not claiming to have the answers, and I apologize if I gave the impression that I did, I am just trying to point out that the gaps in our knowledge are wide, and happen to fall within a hole in our existing vaccine research.
I don’t know what you mean by “regulatory capacity” but as far as reduced immune response, covered in Dr. Offit’s paper.
It isn’t a reduced immune response; it is more like an impaired ability to control the immune response. Think of it like this, at pathogen recognition time a lot of chemical signals go out, some are to bring in the bombers, but others are to call the bombers off. It’s dangerous to just invoke inflammation all happy go lucky without a plan to tone things down; i.e., when SBM posts something about the problems with a supplement to ‘boost your immune system’; they’ve got a good point. You don’t want things persistently boosted, but in autism, we seem to see decreases in substances known to participate in controlling the inflammatory response.
So, in the autism realm, when we see decreased levels of MET, or decreased IL-10 production (in vitro), or decreased levels of TGF-B1, these chemicals are part of the signal mix that reduces the inflammatory response. I mentioned this on the SFARI site in response to you, the Garbett paper on the immune transcriptome in the brain has a part that the genetic activation profile observed is consistent with ‘an inability to attenuate the cytokine activation signal’ So while we don’t know what is causing the chronic microglial activation in autism, we do have some experimentally driven data points that indicate a problem with controlling the immune response is participating.
Regarding, http://www.ncbi.nlm.nih.gov/pubmed/22917523
1) Do you have a copy? 🙂
2) IL-10 is a regulatory cytokine; in other words, if you have less of it, you have a reduced regulation capacity for the inflammatory response. Regulatory T Cell-Derived Interleukin-10 Limits Inflammation at Environmental Interfaces
This kind of speaks towards my point; kids with autism have a reduced capacity to ‘limit inflammation’; maybe we should think twice before initiating it?
Similarly, IL-4 is a regulatory cytokine, i.e., Anti-inflammatory effects of IL-4 and IL-10 on Human Polymorphonuclear Leukocytes
If you wanted to make the point that children with autism have impaired regulatory capacities at birth, you picked a good reference to highlight that fact! Did you see anything in Dr. Offit’s paper about a subpopulation of chidlren with reduced capacities to regulate inflammation? Might we want to approach that subgroup differently, or is our only concern b cells and counting antigens?
3) This paper doesn’t deal with the values at response time; i.e., stimulating the blood with LPS/POLY:IC, just a baseline measurement. It still looks pretty neat, but it doesn’t tell us about the degree of immune response we might get from something like Altered T cell responses in children with autism
Are microglia activated for every trigger of the innate immune system?
I don’t know; probably it depends on a lot of factors, the dose, the specific patterns being recognized, the baseline and a billion other things. As I stated before, this interaction is a relatively new understanding.
Also, does this induce chronic inflammation?
This was not evaluated in this study; however, some of the same group did write a very cool paper that I’ve linked to a bunch, Postnatal inflammation increases seizure susceptibility in adult rats, which found time dependent changes in brain function as measured by seizure susceptibility in rats with unmitigated immune responses, if the insult occurred within specific timeframes. That’s the pattern that seems to be coming from the animal studies; there are time frames of maleability. This is why analysis on the MMR tells us about the MMR, but doesn’t help us understand things that happen a lot earlier.
Is it the same type of activation or in the same region of the brain.
Good question. The ‘type of activation’ is almost certainly an unkonwn, and there appears to be an ongoing debate about the number of different activation statuses of microglia, and they appear to be time and spatially dependent, amoung other things. Take a look at the Konat paper I linked above regarding a ‘broad upregulation of cerebral cytokines’ following peripheral challenge for some more insight into what we do know.
How about triggering the adaptive immune system. We are talking about vaccines, right? Why did you move away from the topic?
Because you cannot do that unless you first trigger the innate immune system! That’s the deal, you don’t get to a place where you present an antigen to a B-cell, unless you have already triggered the innate immune system. Why do you think they put aluminum in vaccines,the b-cell memory banks could care less for it; but for some reason, it insures a robust innate immune respnse.
If you don’t think vaccines trigger the innate immune system, why are fevers a common side effect?
Look, there is evidence for it here, Effect of influenza vaccine on markers of inflammation and lipid profile
We drew blood from 22 healthy individuals 1 to 6 hours before they were given an influenza vaccination and 1, 3, and 7 days after the vaccination. Plasma CRP, interleukin (IL)-6, monocyte chemotactic protein 1, tumor necrosis factor alpha, IL-2 soluble receptor alpha, and serum amyloid A were measured, and differences in mean concentrations of absolute and normalized values on days 1, 3, and 7 were compared with mean baseline values. There was a significant increase in mean IL-6 (P < .01 absolute values, P < .001 normalized values) on day 1 after receiving the influenza vaccine. The mean increases in normalized high sensitivity CRP values were significant on day 1 (P < .01) and day 3 (P = .05), whereas the mean increase in normalized serum amyloid A was significant only on day 1 (P < .05)
That is the kind of thing I’d love to see from our vaccine schedule, when futuredave5 talked about studying the medical side of it, that is where we shoud be headed, in my opinion. Try to find something like this for an infact vaccine, or the schedule. There just isnt’ anything there.
Your point sounds interesting up until the point where one realizes that there are so many open questions as to render the statement nearly useless.
The narrative is that we understand the possible side effects of vaccination as a process; I believe this is a false narrative; especially given the completely flacid, utility free metrics of multiplying B cell capacities and counting antigens.
– pD
Hi Sullivan –
Something you said earlier got me thinking about other things I’ve seen you say. In response to a study on a neuroimmune response in the brain, you asked;
Is it the same type of activation or in the same region of the brain.
I would submit that this question shouldn’t matter.
I’ve seen you post in several places something along the lines of ‘uncontrolled testing of anti inflammatories to reduce neuroinflammation are dangerous, as we don’t really know what will happen.’ I happen to agree with you, though we probably disagree on the likelyhood that the neuroimmune environment is pathological in autism. But I do agree that we can’t predict the effects of twinking a system like this; in fact, that is kind of what has me concerned about this whole mess.
The animal studies tell us consistently that there is a cross talk between the peripheral and central immune system, that the messengers of that cross talk include innate immune response molecules, and disrupting that balance has effects; especially in early life. All of this information is brand new, a decade old, or much, much less.
Would you be OK with a finding in rats,where a different part of the brain responds with changed morphology in microglia that what we have observed so far in autism? Would that really be such a relief?
If intentionally trying to alter the neuroimmune state you see on message boards contains risks we don’t understand that concern you, why does it constitute such a big ‘hole’ in my argument when I provide data that immune challenges can have a similar effect? Are we so certain of the neuroimmune profile in infancy versus autism childhood that make one action without possible consequence, and the other is an experiment with great unknowns?
Take a look at Microglia in the developing brain: a potential target with lifetime effects
It is a recent review from a NIH researcher. The is extensive discussion regarding how little is known about microglial proliferation and phenotype development in the womb and postnatal stages, there is a lot on the time dependent nature of alterations to microglial development. Take a look at how many papers he puts forth as an argument, and then consider the relative strength of the arguments put forth in the Dr. Offit paper you linked to earlier. I would encourage anyone who reads this thread to read Microglia in the developing brain, and consider the question of if B cell capacity is a meaningful metric in this discussion or not.
I take it you aren’t reading what the researchers in the field–namely those from Hopkins–have to say. It isn’t me whom is saying care should be taken with attempting to “treat” neural inflammation, it’s them. Their FAQ is very clear. The chapter they wrote for a recent textbook is very clear. It is clear that care needs to be taken in pursuing treatments and that some of the treatments considered will have no effect on the situation.
That is not to say that they are not pursuing the avenue. They are. It is one thing to do an actual experiment and monitor for improvement and signs of change and another to just pull out the prescription pad and hope for the best.
” I would submit that this question shouldn’t matter.”
In some response from you it’s a good question and in another response it doesn’t matter. Forgive me for moving on, especially since elsewhere you make assumptions about what I think which are not based on what I’ve said.
To respond to your final statement consider a person with no b-cells. Give him/her a vaccine. I put it to you that person will consider b-cells highly relevant to the discussion.
What you have failed to do is take the information you claim to understand and do the math–show your work as I suggested–to demonstrate that some other factor is the limiting agent in how many vaccines a body can respond to. Until you do that, it’s all hand waiving.
Hello Ellie/CIA Parker…still ranting on about vaccines? You are being moderated for your thread-derailing tactics, for comment spamming and for your use of Sockies. Just go away now.
@pD: You certainly “did uncomplicate” Dr. Offit’s explanation of the humoral B lymphocyte response to vaccines, with your walls of copy pasted text lifted from a bunch of science articles. (I have never read such a gmish of sciency sounding words and phrases to explain to parents/laypersons the B lymphocyte humoral response to an antigen or pieces of antigens contained in vaccines).
How about this article from the NIH-National Institute of Allergy and Infectious Diseases to explain to parents/laypersons how vaccines and the humoral response system work?
http://www.niaid.nih.gov/topics/vaccines/understanding/pages/howwork.aspx
Hi lilady –
If my explanation left you confused, I am sorry. Perhaps the problem lay in your apparent misunderstanding of my intent; it was no to ‘uncomplicate’ that paper, but rather, to provide a brief illustration of why there is no logical reason to select ‘the capacity to respond to extremely large numbers of antigens ‘ as a starting and ending point in a discussion on if vaccines could ‘overwhelm’ the immune system.
So perhaps that is part of the problem.
If some of the words or concepts in the papers I linked to or quoted were confusing, you might goto pubmed, type in the confusing word or concept, and read some of the underlying papers.
Thanks for the link; hey, do you have any ideas why Dr. Offit didn’t mention Helper T cells in the discussion on whether vaccines can overwhelm the immune system? I mean, they are right there in the link you provided, they ‘assist in activating killer T cells, and helper T cells also stimulate and work closely with B cells.’, and yet, for some curious reason, they were completely absent from Dr. Offit’s explanation regarding a ‘capacity to respond to extremely large numbers of antigens’. It seems to me that if B and T cells are interacting, our explanation might want to consider those too. But what do I know?
– pD
IMO, I think you made you “intent” abundantly clear pD. Your “intent”, was to obfuscate and complicate Dr. Offit’s simple explanation of the humural B lymphocyte reaction to whole antigens and the pieces of antigens that are contained in vaccines, geared to parents/laypersons. In addition, you clearly state in your reply to Matt Carey that…”I am not writing an article designed for parents who know nothing about immunology who are worried about vaccinations. In order to illustrate the complexity of a system, a system that cannot be adequately described through multiplication, the details are necessary.”
May I suggest to you that you are among the parents “who know (little) or nothing about immunology”? Clearly, you have quote mined bits and pieces of articles that you found on PubMed to fit into your numerous “What ifs?” hypotheses.
You further state, “…hey, do you have any ideas why Dr. Offit didn’t mention Helper T cells in the discussion on whether vaccines can overwhelm the immune system? I mean, they are right there in the link you provided, they ‘assist in activating killer T cells, and helper T cells also stimulate and work closely with B cells.’, and yet, for some curious reason, they were completely absent from Dr. Offit’s explanation regarding a ‘capacity to respond to extremely large numbers of antigens’. It seems to me that if B and T cells are interacting, our explanation might want to consider those too.”
I’m willing to make an educated guess about Dr. Offit’s concentration on the function of B lymphocytes which when stimulated by antigens make the antibodies. T cells do not make antibodies. Alternatively, you could pose the question to Dr. Offit at CHOP.
“But what do I know?” I don’t know what your knowledge base is or why you are complicating Dr. Offit’s simple explanation of the humoral response to the antigens/pieces of antigens contained in childhood vaccines. I also do know why you think your many “What ifs” hypotheses and quotes from sciency papers, constitute a scientific article.
@ futuredave5: I realize that you are a layperson who is trying to understand why vaccines are necessary and trying to separate what are reliable websites and which are not.
Again, the ANA test done in the absence of specific symptoms of connective tissue disorders/auto immune disorders is not indicated.
I don’t understand why your child’s physician is ordering titers to see if your child needs additional shots. It is not recommended for a child (*with rare exceptions) because the Recommended Childhood Vaccine Schedule is devised to provide the maximum protection for each vaccine-preventable disease:
Click to access parent-ver-sch-0-6yrs.pdf
The “Recommendations” are subject to change, and it’s not just the addition of new vaccines. A second MMR vaccine was recommended, following epidemiological investigations of major measles outbreaks that occurred late 1980s-early 1990s. Many of the children who contracted measles actually had 1 dose of MMR vaccine, yet they were among the 5 % of kids who did not have protective titers. That is the reason why the newly developed Tdap vaccine is on the Schedule for children entering 7th grade or older school children. Again epidemiological studies have found there is secondary vaccine failure a.k.a. waning immunity in children who received all five doses of pertussis vaccine. Waning immunity is also a problem for those of us who had pertussis in early childhood, as well. Hence the “Recommendations” for the Tdap vaccine for all HCWs, childcare workers, parents, grandparents, older family household members who have contact or expect to have contact, with infants under the age of one.
High fevers after a prior immunization are not a contraindication to receiving another shot. A febrile seizure, even though it does not lead to permanent neurological impairment is not contraindication to receiving another dose of vaccine…it may be listed as a “cautionary factor”.
Here’s the website for the 2012 edition of the CDC Pink Book (Do NOT download the entire book because it is an immense PDF file). You can download each chapter to find out some of the answers to your questions about each vaccine.
http://www.cdc.gov/vaccines/pubs/pinkbook/index.html
*The exception to testing vaccine recipients for immunity would be a child born of a hepatitis B carrier mother whose hepatitis B vaccine doses are tracked by the local health department and who should be tested following the completion of the vaccine series. If the child has no immunity (~ 2-3 % of children who are tested), then the child should complete another series of the vaccine and be retested…most of the children do sero-convert. This is done because children have an ongoing risk of contracting the virus through horizontal transmission because of constant close exposure to a chronic hepatitis B carrier.
Lilady: I think the doctor was just trying to follow our instructions. We said that we were concerned about the reaction he had to the last vaccine, and wanted to avoid it unless there were areas where his immunity was insufficient.
i think the doctor understood our concern. In all fairness, though, if he had not, we would have found a different doctor that did. We have spoken with two other doctors about this process since then, with various degrees of support.
Even the doctor who supports the current CDC immunization still agrees with our right, as parents, to adjust our son’s immunization schedule, as long as we do it based on facts rather than opinions we pull from the web.
We have an appointment with her next month, but I don’t want to go in with a bunch of random crazy theories.
Mr. Carey,
Although it may seem “the medical establishment has caught on to Sears”, they really haven’t done anything to reign in him or Jay Gordon, another unethical pediatrician who hide behind the silence of the American Academy of Pediatrics, who refuse to condemn these two of their own who are seriously dropping vaccine rates in the US. Please check outhttp://www.stopsearsandgordon.org/index.html for more information.
Chris Hickie, MD, PhD
Tucson, AZ
All of us who are pro-vaccine and pro-science do our part, Dr. Hickie…Mr. Carey by his participation on the IACC (Interagency Autism Coordinating Committee) and with his blogging and analyses of studies.
*Others* have posted at Dr. Bob Sears on the Ho-Po and posted at Dr. Jay, when he deigns to honor us on the Respectful Insolence blog. Poor Jay, he gets so frustrated when *other posters* use the misinformation about vaccines that he posts on his own website, to point out to him what a publicity-seeking tool he really is. 🙂