Autoimmune syndromes induced by adjuvants – Shoenfeld vaccine myth

One of the enduring myths (there are so many) about the HPV vaccine is that it is linked to one or more autoimmune syndromes, an abnormal immune response to a healthy body part. These claims, pushed by an Israeli physician, Yehuda Shoenfeld, are called “autoimmune syndrome induced by adjuvants (ASIA)” and, sometimes, Shoenfeld’s Syndrome. 

But we call it a myth, a lie, pseudoscience, and quackery. Despite the rejection of Shoenfeld’s bogosity by scientists worldwide, he was recently elected to the Israeli Academy of Sciences and Humanities. What were they thinking?

But let’s get back to ASIA – it is not accepted by the scientific and medical community (and see this published article), was rejected by the United States vaccine court as a claim for vaccine injury, and should not be accepted by parents deciding whether they should vaccinate their children.

Furthermore, the European Medicines Agency, which is the primary regulatory body in the EU for pharmaceuticals, has rejected any link between the HPV vaccine and various autoimmune disorders. The science stands in direct opposition to autoimmune syndromes being caused by any vaccine.

The World Health Organization (WHO)  has scientifically rejected the quackery of ASIA (if it even exists) is caused by vaccines, notably, the HPV vaccine.

Despite the lack of evidence supporting the existence of autoimmune syndromes induced by adjuvants, and even more powerful evidence that it doesn’t exist, the anti-vaccine religion still cherry-picks articles to support their preconceived conclusions that the HPV cancer-preventing vaccine is dangerous.

So, let’s take a look at Yehuda Shoenfeld and his ridiculous ASIA claims. Then we’ll criticize the Israeli Academy of Sciences and Humanities for seemingly endorsing his junk science.

autoimmune syndromes

All about HPV and HPV vaccines

I know I add this section to every article I write about HPV vaccines. It is updated almost every time with additional information about HPV or the vaccine. Moreover, there are readers who want to know more about HPV, and this section can help someone get up-to-speed quickly.

Genital and oral human papillomavirus (HPV) infections are the most common sexually transmitted infections (STI) in the USA.  HPV is generally transmitted from personal contact during vaginal, anal or oral sex.

It’s important to note that there are more than 150 strains or subtypes of HPV that can infect humans – however, only 40 of these strains are linked to one or more different cancers. Of those 40 strain, most are fairly rare.

Although the early symptoms of HPV infections aren’t serious and many HPV infections resolve themselves without long-term harm, HPV infections are causally linked to many types of cancers in men and women. According to current medical research, here are some of the cancers that are linked to HPV:

In addition, there is some evidence that HPV infections are causally linked to skin and prostate cancers. The link to skin cancer is still preliminary, but there is much stronger evidence that HPV is linked to many prostate cancers.

HPV is believed to cause nearly 5% of all new cancers across the world, making it almost as dangerous as tobacco in that respect. According to the CDC, roughly 79 million Americans are infected with HPV – approximately 14 million Americans contract a new HPV every year. Most individuals don’t even know they have the infection until the onset of cancer. The CDC also states that over 43,000 HPV-related cancers are diagnosed in the USA every year. It may be several times that amount worldwide.

There were two HPV vaccines on the world market before 2014. GSK, also known as GlaxoSmithKline, produced Cervarix, a bivalent (protects against two HPV strains) vaccine. It has been withdrawn from the US market (although available in many other markets), because of the competition from the quadrivalent (immunizes against four different HPV strains) and 9-valent (against nine HPV strains) Gardasil vaccines.

Merck manufactures Gardasil, probably the most popular HPV vaccine in the world. The first version of the vaccine, quadrivalent Gardasil, targets the two HPV genotypes known to cause about 70% of cervical cancer and two other HPV genotypes that cause genital warts. In Europe and other markets, Gardasil is known as Silgard.

The newer Gardasil 9, approved by the FDA in 2014, is a 9-valent vaccine, protecting against HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58. It targets the four HPV strains found in the quadrivalent version, along with five additional ones that are linked to cervical and other HPV-related cancers. Both versions of Gardasil are prophylactic, meant to be given to females or males before they become exposed to possible HPV infection through intimate contact.

Gardasil is one of the easiest and best ways to prevent a few dangerous and, to abuse the definition slightly, common cancers that afflict men and women. Without a doubt, the HPV vaccine prevents cancer.

Currently, in the United States, the Advisory Committee on Immunization Practices (ACIP) recommends that preteen girls and boys aged 11 or 12 are vaccinated against HPV. The immunization is also recommended for teenage girls and young women up to the age of 26 who did not receive it when they were younger, and teenage boys and young men up to the age of 21.

Let me sum this all up so that if you come away from this section with nothing else, you get this summary. HPV is a sexually transmitted disease. HPV causes 43,000 cancers a year in the USA alone. The HPV vaccine prevents becoming infected by HPV, which means you are protected from these cancers.

autoimmune syndromes
The Lungshan Temple in Taiwan, located in Asia, the continent. Not ASIA, the quack medicine. Photo by Charles Postiaux on Unsplash.

Autoimmune syndromes induced by adjuvants “study”

In a study published in the low impact factor journal, Immunologic Research, the authors reviewed, Jara et al., the literature that claims that ASIA is a real issue. To be clear, this is a review article, but it is not a systematic or meta-review, which sits at the top of the hierarchy of medical research.

Basically, Jara et al. reviewed 4479 ASIA cases, from 2011 to 2016, which included 305 “severe” cases, along with 11 deaths. They claim that the severe ASIA cases were related to the HPV cancer-preventing vaccine, silicone, flu vaccine or mineral oil injections. The 4479 cases were culled from published articles over that time period.

The authors then conclude:

Efforts should be made to discover the connection between adjuvants, autoimmunity and autoimmune diseases, because there is an increase in cases severe and life-threatening of ASIA.

You might think this is a definitive “proof” that ASIA exists, and it’s caused by vaccines (mostly the HPV vaccine, but also adjuvants in general along with the flu vaccine). To disabuse anyone from assuming this conclusion is accurate, let’s critique this study from an unbiased scientific perspective:

  • This was not a systematic review. It did not establish whether any of the articles actually showed evidence of causality between the vaccines/adjuvants and autoimmune diseases. It did not include huge studies that have shown no relationship between the HPV vaccine and autoimmune diseases.
  • This study makes absolutely no effort to compare results to a control group, say the general population. ASIA-like symptoms are found at the same (and sometimes higher) rate in the unvaccinated population as the vaccinated one. In other words, ASIA may be a syndrome that’s simply found in individuals irrespective of vaccine status. All of the studies included in this “review” lacked adequate controls that might establish a causal link between vaccines and ASIA.
  • The study relies on 40 published articles only. Worse yet, 19 of those studies were authored or co-authored by Yehuda Shoenfeld, who has a vested interest in “proving” that ASIA exists. These studies seem to indicate a high level of bias of the authors, as if they were trying to find the published research that established a link, rather looking at all of the research to see if there is even a link.
  • Sixteen of the 40 studies cited had nothing to do with vaccines or adjuvants – most of them were trying to link silicone breast implants to ASIA, not vaccines. It’s possible that the authors were trying to imply that silicone is a vaccine adjuvant, but as far as I can tell, it is not used as such.

This study does not actually provide us with any data to conclude that vaccines are causally related to autoimmune syndromes induced by adjuvants. At best, it provides us a list of studies that can be cherry-picked which can be used to ignore the well-designed epidemiological studies that actually provide overwhelming evidence that there is no link between the HPV vaccine and various autoimmune diseases.

Obligatory cute puppy photo. It has nothing to do with ASIA or Shoenfeld either. Photo by Jametlene Reskp on Unsplash

Another HPV vaccine and autoimmune disorders study

A while ago, I reviewed another study, which was a properly designed case-control epidemiological study. According to the study published in the Journal of Autoimmunity, HPV vaccines do not increase the risk of developing autoimmune diseases (ADs). This adds to the body of research, based on a methodology that helps us establish correlation and causation, that rejects the hypothesis that the HPV vaccine is related to ASIA.

In this study, the authors evaluated the risk of autoimmune diseases over 6.5 year period after exposure to HPV vaccines (quadrivalent Gardasil and bivalent Cervarix) in adolescent and young adult women using data from a French medical registry, Pharmacoepidemiologic General Research eXtension (PGRx). The PGRx is a surveillance database that helps researchers monitor the occurrence of rare or delayed health events that may be related to the use of medications, including vaccines.

Here are the published results of the study:

  • A total of 478 cases with AD against 1869 matched controls with no AD were included in the case-control study. A large majority of individuals in both the AD and control groups had received the quadrivalent Gardasil vaccine (95.3%). Additionally, over half of the study population had been exposed to at least one other vaccine during the 24 months before inclusion in the study
  • The HPV vaccine uptake rate was lower in the patients with AD than in the controls without AD (10.9% vs 22.5%).
  • Surprisingly, the group receiving an HPV vaccine had a more than 40% lower observed risk of developing AD. A similar lowered risk of central demyelination/multiple sclerosis (CD/MS) and autoimmune thyroiditis (AT) was observed in the HPV vaccine group. The researchers observed a statistically nonsignificant trend for reduced risk of connective tissue disease (CTD) and type 1 diabetes (T1D) after vaccination.
  • No correlation was found between HPV vaccine exposure and idiopathic thrombocytopenic purpura (ITP). The relationship between HPV vaccine exposure and Guillain-Barré syndrome (GBS) could not be established since no cases of GBS occurred in individuals who received an HPV vaccine.

The authors concluded:

Exposure to HPV vaccines was not associated with an increased risk of ADs within the time period studied. Results were robust to case definitions and time windows of exposure. Continued active surveillance is needed to confirm this finding for individual ADs.

This data not only shows us that there is no link between the HPV vaccine and autoimmune diseases but, in a few cases, seems to indicate that there is a higher risk of these autoimmune diseases in the non-vaccinated group.

More autoimmune disorders quackery from Shoenfeld

Shoenfeld has published over 60 articles on adjuvants and autoimmune disorders. For even a top-level science researcher, that would be impressive at the meta level. However, there are many issues:

  1. Most of the studies are published in low impact factor journals, which often have low or no peer-review, or even in predatory journals that publish any article as long as they are paid. On the other hand, none of his articles are published in the premier journals for autoimmune disease, like The Journal of Allergy and Clinical Immunology or the Annals of the Rheumatic Diseases. If these anti-vaccine “researchers” actually had groundbreaking work that is supported by robust data, these journals would be begging to publish it.
  2. Almost all of his publications are opinion pieces or reviews (not systematic reviews) that don’t contribute data that could be used to further the science behind Shoenfeld’s claims. I’ve noticed this a lot with anti-vaccine “science” – they provide very little in data, but a lot in rhetoric.
  3. Shoenfeld receives much of his research funding from the Children’s Medical Safety Research Institute (CMSRI), which was founded by the Dwoskin Foundation, who also supports the research from the oft-retracted team of Christopher Shaw and Lucija Tomljenovic.
  4. Of course, one of his studies, co-authored with the aforementioned Shaw and Tomljenovic, was retracted as a result of a “review by the Editor-in-Chief and evaluation by outside experts, confirmed that the methodology is seriously flawed, and the claims that the article makes are unjustified.”
  5. In the rare studies that are backed by original data, Shoenfeld seems to rely upon small animal studies or case studies, both near or at the bottom of the hierarchy of biomedical research. Their value as evidence needs to be supported by real clinical research.

Vincent Iannelli’s blog, Vaxopedia, has a much more in-depth criticism of Shoenfeld, it is worth a read. Dr. Iannelli concludes that “it is the ‘actual science’ of his studies that is ‘being methodologically assessed and critiqued.’ And it has been found to be lacking.”

Obligatory cute kitten photo which also has nothing to do with vaccines. It’s just a cute photo. Photo by Anton Kraev on Unsplash.

Shoenfeld is just wrong

But here’s the most important thing that both Dr. Iannelli and I agree on – large clinical and epidemiological studies have found no safety signals for autoimmune syndromes from HPV vaccines. Several studies shown no link between the HPV vaccine and autoimmune syndromes.

A recent systematic review, that included over 73,000 patients, found no difference in autoimmune syndromes between vaccinated and unvaccinated groups.

Another large study of over 1 million women found no safety signals for autoimmune diseases, neurological and venous thromboembolic (venous blood clots) events in HPV vaccinated women. The researchers deduced that,

This large cohort study found no evidence supporting associations between exposure to qHPV vaccine and autoimmune, neurological, and venous thromboembolic adverse events. Although associations for three autoimmune events were initially observed, on further assessment these were weak and not temporally related to vaccine exposure. Furthermore, the findings need to be interpreted considering the multiple outcomes assessed.

A recent meta-review (considered the pinnacle of biomedical research) of over 100 different safety studies of the HPV vaccine, that included over 2.5 million individuals, found no increased risks of adverse events of special interest (AESI), which are events that can cause serious harm. The authors of this study concluded that,

There was no consistent evidence of an increased risk of any AESI, including demyelinating syndromes or neurological conditions such as complex regional pain or postural orthostatic tachycardia syndromes. The risk-benefit profile for HPV vaccines remains highly favourable.

These aren’t case-studies or torturing mice for results – these are huge studies that include millions of data points. And these were published in predatory journals that require payment to get your nonsense published – these are important, high impact factor journals that are respected across the world.

Science wins.

Israel is a lovely country. But its Academy of Sciences and Humanities is wrong. Photo by Thalia Tran on Unsplash

Shoenfeld elected to the Israeli Academy of Sciences and Humanities

If only Yehuda Shoenfeld and his quackery would just go away, but alas, that’s not going to happen apparently. In a remarkably boneheaded and laughable decision, the Israeli Academy of Science and Humanities has elected this anti-vaccine nut job to its ranks. The Academy is a very distinguished institution, considering it represents a tiny country, filled with world-renowned scientists, including numerous Nobel Prize winners.

These academies are important to fostering science. One of the most prestigious science academies in the world is the United States’ National Academy of Sciences. One of the constituent organizations in the Academy is the National Academy of Medicine which is overwhelmingly pro-vaccine would never include a pseudoscientist like Shoenfeld. It would be like adding that fraud Andrew Wakefield to the National Academy of Medicine – at that point, no real scientist would listen to them.

And that’s what many of us think about this election. If the Israeli Academy of Sciences and Humanities adds the discredited crackpot Shoenfeld to their rolls, then what does that mean about the quality of science in that institution? Well, to me, it means that I ignore everything they ever write and say about anything unless it’s supported by real science from a respected institution.

I know some will argue that Shoenfeld is some “great scientist,” and I’m just pushing a pro-vaccine narrative that dismisses his greatness. But, as I have said at least 47 billion times, the only thing that matters is evidence. And the evidence shows that Shoenfeld is an anti-vaccine quack.

But don’t believe me, let’s turn to the indefatigable Orac (worth a full read, because he really hits the nail on the head as to why this is a ridiculous move):

Shoenfeld even wrote an article entitled “Everything Is Autoimmune Until Proven Otherwise“. Of course, ASIA is a manifestation of that idea, which is cringeworthy in its echoing of the common quack tendency to ascribe all diseases to The One True Cause of Disease. Of course, it doesn’t help that he has appeared to speak at conferences that can only be described as clearly antivaccine, such as ones sponsored by the Children’s Medical Safety Research Institute (CMSRI), a now-defunct antivaccine “institute” formerly funded by the Dwoskin family and dedicated to funding antivaccine “research.”

First of all, saying “something is something until I’m proven otherwise” is unscientific. It is a logical fallacy. It is just what a pseudoscientist would say. Furthermore, as I wrote above, we have boatloads of evidence that has established that vaccines are NOT LINKED TO AUTOIMMUNE SYNDROMES

Second, he was supported by notorious anti-vaccine money. He is a shill for the anti-vaccine religion. 

But why trust a couple of pro-vaccine bloggers who obviously think that vaccines are very safe and very effective. Let’s go with a couple of peer-reviewed papers that are critical of ASIA, written by a clinical immunologist, Rohan Ameratunga. In the first one, Dr. Ameratunga states:

Current data do not support the causation of ASIA by vaccine adjuvants containing aluminum, which should be of reassurance to patients undergoing routine immunizations as well as to those undergoing allergen-specific IT.

And in the second paper, he concludes:

We have recently reviewed ASIA as defined by its authors. We have shown that the definition of ASIA is imprecise and includes all patients with an autoimmune disorder as well as potentially the entire population. Application of the Bradford Hill criteria for causality does not support ASIA as an outcome of exposure to aluminium containing adjuvants in vaccines. The advocates of ASIA highlight animal models as evidence for the existence of the disorder. However, as this review will demonstrate, animal models purporting to support the existence of ASIA have methodological, analytical and ethical flaws which, in our view, refute the existence of the condition.

In other words, ASIA has been rejected over and over and over and over by important scientists across the world.

But that’s not the worst of it. Smut Clyde, the nom de guerre of a frequent commenter to this blog wrote:

So Shoenfeld is identified with the anti-vaccine lobby, at least in the minds of anti-vaccine True Believers. His is the name most touted in tweets as proof that Real Science is on their side (with Drs Exley, Shaw, Gherardi and Luján as lesser authorities). I feel safe in predicting they will make the most of his induction into Israel’s Academy of Sciences as a vindication of everything they have said.

Yes, because the anti-vaccine zealots love to utilize the appeal to false authority logical fallacy over actual evidence. And Mr. Clyde points out something very important – in general, most of us couldn’t care less who the Israeli Academy of Sciences and Humanities does or does not elect to its group. It’s not that relevant to the world of science, except when it is.

The anti-vaxxers will use this as an endorsement of Shoenfeld’s ignorant claims. Maybe it is. Maybe it isn’t. Maybe someone at the Academy didn’t do a proper Google search. Maybe it’s some sort of reverse anti-Semitism, though if the Academy took a nanosecond to examine the virulent anti-Semitism of the anti-vaxxers, they’d take pause in endorsing any anti-vaccine belief.

Orac concludes his thorough article by saying:

 Having Yehuda Shoenfeld as a member of the Israeli Academy of Sciences and Humanities is a blight on the Israeli science community and will be used by antivaxers to promote their pseudoscience.

Absolutely.

Conclusion

There is robust and overwhelming evidence that HPV vaccines are not related to autoimmune syndromes. These are large, well-controlled and well-designed studies, not biased “reviews” of biased research. There is simply no known link between HPV vaccines and autoimmune syndromes induced by adjuvants.

The HPV vaccines, like Gardasil, help prevent some serious and dangerous cancers. I’m hoping parents begin to understand that there are few if any risks for the vaccine, with the substantial benefit of preventing cancer.

ASIA is a bogus claim from anti-vaccine quack Yehuda Shoenfeld to make it appear to be a dangerous adverse effect of vaccines. And his election to the Israeli Academy of Sciences and Humanities will be used by the anti-vaccine religion to denigrate vaccines, especially the cancer-preventing HPV vaccine.

Shoenfeld’s pseudoscience has seemingly been endorsed by the Israeli Academy. And we will be bludgeoned by the anti-vaxxers for that. Lucky for us, we have science on our side. 

Editor’s note – this article was published on May 2017. It was updated to include more information about Shoenfeld, including his election to the Israeli Academy of Sciences and Humanities, since he’s the key proponent of this pseudoscientific claim about the HPV vaccine. In addition, new citations, heavy copyediting, some reformatting, and various other things were done to clean up the article.

Citations



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The Original Skeptical Raptor
Chief Executive Officer at SkepticalRaptor
Lifetime lover of science, especially biomedical research. Spent years in academics, business development, research, and traveling the world shilling for Big Pharma. I love sports, mostly college basketball and football, hockey, and baseball. I enjoy great food and intelligent conversation. And a delicious morning coffee!