Eitan Israeli

Vaccines and autoimmunity.

Vaccines have been used for over 200 years and are the most effective way of preventing the morbidity and mortality associated with infections. Like other drugs, vaccines can cause adverse events, but unlike conventional medicines, which are prescribed to people who are ill, vaccines are administered to healthy individuals, thus increasing the concern over adverse reactions. Most side effects attributed to vaccines are mild, acute and transient; however, rare reactions such as hypersensitivity, induction of infection, and autoimmunity do occur and can be severe and even fatal. The rarity and subacute presentation of post-vaccination autoimmune phenomena means that ascertaining causality between these events can be difficult. Moreover, the latency period between vaccination and autoimmunity ranges from days to years. In this article, on the basis of published evidence and our own experience, we discuss the various aspects of the causal and temporal interactions between vaccines and autoimmune phenomena, as well as the possible mechanisms by which different components of vaccines might induce autoimmunity.

Vitamin D: a new anti‐infective agent?

Before the antibiotic era, treatment of tuberculosis patients was restricted to sun exposure in sanatoria. Years later, it was found that 1,25‐dihydroxyvitamin D3 stimulates production of cathelicidins, a family of polypeptides found in lysosomes of macrophages and polymorphonuclear leukocytes. Cathelicidins serve a critical role in innate immune defense, which plays an important role in the suppression of Mycobacterium infections and other pathogens. It is believed that the increased incidence of the common cold and pneumonia during winter is related, in part, to decreased exposure to sunlight, resulting in a decreased synthesis of 1,25‐dihydroxyvitamin D3. An association has been established between low levels of vitamin D and upper respiratory and enteric infections, pneumonia, otitis media, Clostridium infections, vaginosis, urinary tract infections, sepsis, influenza, dengue, hepatitis B, hepatitis C, and HIV infections. Accumulating evidence suggests that 1,25‐dihydroxyvitamin D3 exerts protective effects during infections by upregulating the expression of cathelicidin and β‐defensin 2 in phagocytes and epithelial cells. Vitamin D may be acting as a panaceal antibiotic agent and thus may be useful as an adjuvant therapy in diverse infections.

The sick building syndrome as a part of the autoimmune (auto-inflammatory) syndrome induced by adjuvants

Sick building syndrome (SBS) is a term coined for a set of clinically recognizable symptoms and ailments without a clear cause reported by occupants of a building. In the 1990s the term “functional somatic syndromes” was applied to several syndromes, including SBS, multiple chemical sensitivity, repetition stress injury, the side effects of silicone breast implants, the Gulf War syndrome (GWS), chronic fatigue syndrome, the irritable bowel syndrome, and fibromyalgia. Recently, Shoenfeld and Agmon-Levin suggested that four conditions—siliconosis, macrophagic myofascitis, the GWS, and post-vaccination phenomena—which share clinical and pathogenic resemblances, may be included under a common syndrome entitled the “autoimmune (auto-inflammatory) syndrome induced by adjuvants”. Comparison of the clinical manifestations, symptoms, and signs of the four conditions described by Shoenfeld and Agmon-Levin with those described for SBS shows that nine out of ten main symptoms are present in all 5 conditions. Shoenfeld and Agmon-Levin further propose several major and minor criteria, which, although requiring further validation, may aid in the diagnosis of this newly defined syndrome. We propose here that SBS may also be included as a part of “Shoenfeld’s syndrome”.

Infections as a Cause of Guillain–Barré Syndrome

Abstract Guillain–Barre syndrome (GBS) is a rare autoimmune disorder, the incidence of which is estimated to be from 0.6 to 4 in 100,000 people per year worldwide. Often (around one-third of cases) GBS occurs a few days or weeks after the patient has had symptoms of a respiratory or gastrointestinal microbial infection. The disorder is subacute, developing over the course of hours or days up to 3 to 4 weeks. Reflexes are usually lost. GBS is a classical autoimmune disease, because all four major Witebsky-Rose criteria for an autoimmune disease are fulfilled. Viral and bacterial infections are often associated with GBS. About a third of all cases of Guillain–Barre syndrome are preceded by Campylobacter jejuni infection. C. jejuni strains isolated from GBS patients have a lipooligosaccharide (LOS) with a GM1-like structure. Molecular mimicry between LOS and the peripheral nerves as a cause of GBS was demonstrated in animal models of human GBS. Infection with serotype HS:19 of C. jejuni and the class A locus were predictive of the development of GBS. Recent studies have found that influenza illness was associated with higher rates of GBS, and influenza viral structures can induce anti-GM1 (ganglioside) antibodies. Judging from the evidence presented in this chapter, the aetiology of GBS can be multifactorial, as it is in other autoimmune diseases. It involves genetic and environmental factors and may be triggered by infections or vaccinations, and predisposition can be predicted by analysing some of these factors.