Summary: Adjuvants are agents added to vaccines to heighten the immune system response to the primary antigen. The video below presents an excellent lecture by one of the world’s leading experts in autoimmunology. He explains how adjuvants can trigger autoimmune reactions that manifest, months or years later, as autoimmune diseases. His exposition, richly illustrated by published case studies, is valuable for all clinicians regardless of specialty. Practically any tissue in the body, including the brain and vascular system, can be a target for autoimmune attack.

Autoimmunity seems to be the medical issue of our time as environmental and other factors promote a loss of immune tolerance to chemicals, toxic and benign, and to self. The resulting chronic inflammation underlies many conditions beyond the strictly defined autoimmune diseases such as MS, SLE and rheumatoid arthritis. Autoimmune inflammation can play a major role in cardiovascular disease, depression, fibromyalgia and chronic fatigue, migraine, loss of normal apoptosis (leading to malignancy), etc.

Professor Shoenfeld Yehuda, MD, FRCP is head of the Zabludowicz Center for Autoimmune Diseases of Sheba Medical Center (affiliated with Tel-Aviv University), the incumbent of the Laura Schwarz-Kipp Chair for Research of Autoimmune Diseases at Tel-Aviv University, editor-in-chief of the journal Autoimmunity Reviews, and co-editor of the Journal of Autoimmunity. While celebrating vaccination as one of the greatest gifts of medicine in modern times, he explains the mechanism by which adjuvants can trigger autoimmunity. Also in this fascinating lecture he discusses some of the environmental, genetic, endocrine and immune factors that create a susceptibility to autoimmunity in general.

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It appears that many still receive treatment for Lyme disease when comprehensive laboratory tests reveal no objective evidence of infection, or with post-Lyme-disease syndrome when symptoms persist despite objective confirmation that a documented infection has been eradicated. An excellent paper published in the European Journal of Clinical Microbiology & Infectious Diseases offers data showing that the causes of persistent symptoms, often autoimmune, are then missed while patients may be subject to ineffectual and harmful long-term antibiotic treatment. The authors state:

“The symptoms of Lyme borreliosis are similar to those of a variety of autoimmune musculoskeletal diseases. Persistence of complaints is frequently interpreted as unsuccessful antibiotic treatment of Borrelia-associated infections. However, such refractory cases are rare, and re-evaluation of differential diagnoses helps to avoid the substantial risk of long-term antibiotic therapy…Post-Lyme-disease syndrome (PLDS) is characterized by symptoms such as fatigue, myalgia, arthralgia, or dysesthesia/paresthesia. This condition of subjective complaints is defined by a Borrelia associated infection adequately treated with antibiotics while objective findings of other diseases are absent.”

They further note that:

“Persistence of borreliae after antibiotic treatment is frequently suspected in PLDS . Long-term antibiotic regimens are targeted to eliminate spirochetes that might survive in areas less accessible to the immune system. However, evidence of a beneficial effect of such long-term treatment is limited to only a few open studies. On the other hand, several double-blinded controlled trials of patients with Lyme disease or PLDS have shown no benefit after repetitive antibiotic treatment. Moreover, case reports indicate severe complications arising from continuous antibiotic therapy. Autoimmune phenomena have been suspected to occur after successful antibiotic treatment.“

They undertook thorough laboratory and clinical evaluations of 86 patients over a 3.5 year period who were diagnosed with Lyme borreliosis or PLDS, taking great care to discriminate suspected Lyme borreliosis or PLDS from other diseases. such as reactive arthritis,psoriasis arthritis (PsA), or rheumatoid arthritis (RA, Bannwarth’s syndrome other polyneuropathies or radicular compression syndromes, and fibromyalgia. Their data demonstrated Lyme disease in only 9%, and no cases of PLDS (persistent infection after antibiotic therapy) were observed. The authors concluded:

“In summary, the findings of Borrelia assays were frequently inconsistent, and several patients who were treated with antibiotics prior to referral to our institute lacked Borrelia-specific antibodies. Patients with Lyme borreliosis were rare in this study, and no cases of PLDS were observed. Degeneration of the vertebral spine was the most frequent differential diagnosis. Although a definite diagnosis could not always be made, the presence of autoimmune antibodies suggested a pathogenesis separate from borreliosis. The results of this study may help to avoid unnecessary long-term antibiotic therapy and the potentially severe complications resulting from such treatment.”

It is very important for clinicians and patients to be attentive to the increasingly widespread phenomenon of acute infections acting as a trigger for autoimmune symptoms that persist long after the original infection is gone.

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An interesting paper just published in PLoS (Public Library of Science) clarifies one of the mechanisms that account for the recent increase in autoimmune disorders. The authors set out to investigate the possibility of an induced dysregulation of the immune system:

“Repeated immunization with antigen causes systemic autoimmunity… Overstimulation of CD4+ T cells led to the development of autoantibody-inducing CD4+ T (aiCD4+ T) cell[s]…[which became] antigen-specific cytotoxic T lymphocytes (CTL). These CTLs could be further matured by antigen cross-presentation, after which they caused autoimmune tissue injury akin to systemic lupus erythematosus (SLE).”

This essentially means that overexposure to a potential antigen (increased amounts of gluten in hybridized wheat, higher environmental levels of mercury, etc.) can result in sensitization of the immune system with cross-reaction to our own tissues (autoimmune disease). The authors clearly state their conclusion drawn from the evidence:

“Systemic autoimmunity appears to be the inevitable consequence of over-stimulating the host’s immune ‘system’ by repeated immunization with antigen, to the levels that surpass system’s self-organized criticality.”

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Often tests shows anti-gliadin antibodies (AGA; gliadin is the immunoreactive component of gluten) in the absence of celiac disease but with various autoimmune conditions representing the non-celiac manifestations of gluten sensitivity. The authors of a study just published in the Scandinavian Journal of Gastroenterology explore this issue for the elderly.

“…data suggest that AGA positivity [without celiac disease] might be related to distinct disease entities such as allergy and gluten ataxia (loss of muscular coordination with unsteady movements and gait). Our aim here is to explore the clinical relevance of positive AGA in the elderly population.”

The authors correlated positive lab tests for gluten sensitivity with the incidence of depression and rheumatoid arthritis in 2815 individuals aged 52–74 years. What did their data show?

“Rheumatoid arthritis and depression were found significantly more often in AGA-positives than controls. The significance remained even when tTGA-positive and known celiac disease cases were excluded.”

Don’t forget that anti-gliadin antibody tests are not an absolute screen for gluten (or any other food) sensitivity because there are a number of factors that can suppress the expression of antibodies at the time of specimen collection. However, this study shows that if an elderly person is suffering from depression or rheumatoid arthritis the possibility of gluten sensitivity should be investigated.

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Those interested in how image and perception modify gene expression and immune function will appreciate this paper recently published in the journal Psychological Science.

“An experiment…tested the hypothesis that the mere visual perception of disease-connoting cues promotes a more aggressive immune response.”

The experimental subjects were exposed to either photographs depicting symptoms of infectious disease or photographs of guns.

“After incubation with a model bacterial stimulus, participants’ white blood cells produced higher levels of the proinflammatory cytokine interleukin-6 (IL-6) in the infectious-disease condition, compared with the control (guns) condition.”

This may not be the first study to demonstrate this effect, but the authors assert…

“These results provide the first empirical evidence that visual perception of other people’s symptoms may cause the immune system to respond more aggressively to infection.”

It’s well known that though we can cognitively discriminate between a photo depicting infection and the immediate material presence of it, our autonomous physiological response does not. Now consider the significance for autoimmune disease when there is hyperarousal of attention to the possibility of infection. This is one of the reasons why I am convinced that dogmatically insisting on a diagnosis of chronic infection (such as Lyme disease) when the most sensitive and advanced tests provide zero evidence—and at the same time demonstrable autoimmune phenomena are present—is doing patients a disservice.

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The authors of this paper published in the journal Minerva Ginecologica frame the problem:

“Endometriosis is classically described as the presence of both endometrial glandular and stromal cells outside the uterine cavity, mainly in the pelvis. The pathogenesis of this enigmatic disorder still remains controversial despite extensive research. Although multiple theories have been put forth to explain the pathophysiology and pathogenesis of endometriosis, the retrograde menstruation theory of Sampson is the most widely accepted. However, since retrograde menstruation occurs in most of the reproductive age women, it is clear that there must be other factors which may contribute to the implantation of endometrial cells and their subsequent development into endometriotic disease.”

The authors argue that immune dysfunction must be playing an important role:

“There is substantial evidence to support that the alterations in both cell-mediated and humoral immunity contribute to the pathogenesis of endometriosis.

They note that immune dysregulation is associated with inadequate removal of ectopic endometrial cells from the peritoneal cavity.

“Moreover, increased levels of several cytokines and growth factors which are secreted by either immune and endometrial cells seem to promote implantation and growth of ectopic endometrium by inducing proliferation and angiogenesis.”

Finally, they make important observation:

“Endometriosis has also been considered to be an autoimmune disease, since it is often associated with the presence of autoantibodies, other autoimmune diseases, and possibly with recurrent immune-mediated abortion.”

This review published recently in the journal Reproduction concentrates on the role of inflammation:

“It is well recognised that many physiological reproductive events such as ovulation, menstruation, implantation and onset of labour display hallmark signs of inflammation. …Moreover, initiation and maintenance of inflammatory pathways are the key components of many pathologies of the reproductive tract and elsewhere in the body. The onset of reproductive disorders or disease may be the result of exacerbated activation and maintenance of inflammatory pathways or their dysregulated resolution.”

Specifically in regard to endometriosis they observe:

“Recent reports suggest that dysregulation of inflammatory factors play a role in endometriosis-associated reproductive failure…The concentration of inflammatory cytokines (IL1B and TNF) and PGs (PGE2 and PGF2{alpha}) produced by peritoneal macrophages and pro-inflammatory chemokines for monocyte/macrophages and for granulocytes is elevated in women with endometriosis…”

What other evidence might we find of inflammatory and autoimmune phenomena in endometriosis? This paper published in the journal Gynecological Endocrinology begins by noting how common a problem this is:

“Endometriosis affects 10–20% of women during reproductive age and is a common cause of infertility and pain leading to work absenteeism and reduced quality of life.”

The authors studied the correlation of the cytokines interleukin-8 (IL-8), tumor necrosis factor alpha (TNF-α), glycodelin and other factors in the peritoneal fluid with pain reported by patients undergoing laparoscopy, and pain during menstruation and intercourse. The presence of endometriosis was histologically confirmed (microscopic examination of the cellular structure).

What did their data show?

“TNF-α and glycodelin correlated positively with the level of menstrual pain…Patients with severe dysmenorrhoea had increased PF cytokine and marker levels; the difference was significant for TNF-α and glycodelin…TNF-α and glycodelin may thus play a role in endometriosis and the severity of menstrual pain.”

If you are treating or you suffer from endometriosis (or severe dysmenorrhea without a diagnosis of endometriosis), is it important to investigate the autoimmune inflammatory components? This and other evidence indicates that it is.

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In our practice we pay a lot of attention to chronic low grade infections because the inflammation associated with them contributes to a broad range of diseases including autoimmune disorders, diabetes, cardiovascular disease, etc. The gastrointestinal tract is a frequent site of chronic infection, and this paper published in the Annals of the New York Academy of Sciences investigates the link between infection in the upper end of the GI tract—periodontitis—and inflammation:

“Increasing evidence implicates periodontitis, a chronic inflammatory disease of the tooth-supporting structures, as a potential risk factor for increased morbidity or mortality for several systemic conditions including cardiovascular disease (atherosclerosis, heart attack, and stroke), pregnancy complications (spontaneous preterm birth [SPB]), and diabetes mellitus.”

Their survey identifies a ‘smoking gun’ of inflammation:

“Consistent with this hypothesis clinical studies demonstrate that periodontitis patients have elevated markers of systemic inflammation, such as C-reactive protein (CRP), interleukin 6 (IL-6), haptoglobin, and fibrinogen. These are higher in periodontal patients with acute myocardial infarction (AMI) than in patients with AMI alone, supporting the notion that periodontal disease is an independent contributor to systemic inflammation. In the case of adverse pregnancy outcomes, studies on fetal cord blood from SBP babies indicate a strong in utero IgM antibody response specific to several oral periodontal pathogens, which induces an inflammatory response at the fetal–placental unit, leading to prematurity.”

A very good reason to take care of your teeth and gums:

“The importance of periodontal infections to systemic health is further strengthened by pilot intervention trials indicating that periodontal therapy may improve surrogate cardiovascular outcomes…and may reduce four- to fivefold the incidence of premature birth.”

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While the manifestations of autoimmune disease vary according to the tissues attacked and whether cell-mediated or antibody excess dominates (and the particular signalling molecules activated), as immunologists know they are all ‘variations on a theme’. This interesting paper published in the German journal Der Nervenarzt (The Neurologist) details how difficult it is to discriminate “systemic diseases such as lupus erythematosus, sarcoidosis, Behçet’s disease, and Sjögren’s syndrome“ that involve the nervous system. “Neither clinical signs nor additional analyses such as serological findings or cerebrospinal fluid analysis are able to differentiate between the diseases with certainty.” That’s how similar they are. However, it can be done and, most importantly, the functional medicine approach using the latest lab investigations can profile the underlying factors that are specific to each person. This is how we get science-based treatment of the causes rather than suppression with steroids.

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Men, difficulties with urination including pain, retention, even bleeding are sometimes not from the prostate. In a paper published in the Archives of Pathology and Laboratory Medicine the authors state: “Eosinophilic cystitis (EC) is an inflammatory condition of the bladder that has been linked to food allergens, infectious agents, drugs, and other genitourinary conditions…[it] represents a response to a variety of agents and may often be overlooked.” As described in this paper published in Urologia Internationalis, “The clinical presentation of EC is varied. When the lesion is located at or near the bladder neck, it may present as urinary retention.” (Ladies, this condition afflicts you and children as well.)

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This important original study recently published in the prestigious journal Neuropsychopharmacology shows how an immune system attack on the brain gives rise to OCD: “Although serum autoantibodies directed against basal ganglia (BG) implicate autoimmunity in the pathogenesis of obsessive–compulsive disorder (OCD), it is unclear whether these antibodies can cross the blood–brain barrier to bind against BG or other components of the OCD circuit…The results of our study implicate autoimmune mechanisms in the pathogenesis of OCD and also provide preliminary evidence that autoantibodies against BG and thalamus may cause OCD by modulating excitatory neurotransmission.” Only a functional medicine approach comprehensively investigates and addresses the underlying causes of autoimmune disorders in an objective, evidence-based fashion.

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