Autoimmune reaction after vaccination is sporadically reported in the medical literature. Vaccinations are generally safe and have an important role in eradicating endemic diseases worldwide. Nevertheless, the question arises as to whether there is a possibility of post-vaccination autoimmune phenomena. The anti-tetanus vaccine is being used since 1924, and it is part of the recommended immunization schedules for children. There are few reports of autoimmune diseases, such as rheumatoid arthritis and anti-phospholipid syndrome after anti-tetanus vaccination. Herein, we describe four cases, of which we believe, show a clear temporal relation between anti-tetanus vaccination and the appearance of dermatomyositis, systemic lupus erythematosus, type 1 diabetes mellitus and anti-phospholipid syndrome. We also suggest some of the pathogenic mechanisms that promote a pathogenic autoimmune response.

OBJECTIVES: To report a series of five patients who developed systemic lupus erythematosus (SLE) after immunization and review the literature on vaccine-associated connective tissue diseases and the theoretical mechanisms that could explain such an association. METHODS: Uncontrolled retrospective analysis of cases identified sporadically over 7 years at three centers.

RESULTS: In our series of 5 patients, symptoms of SLE developed within 2 to 3 weeks after secondary immunization. All patients met American College of Rheumatology (ACR) criteria for the diagnosis of SLE. In most patients, symptoms have been persistent.

CONCLUSION: Although a coincidental association between vaccination and the onset of SLE cannot be excluded, the temporal relationship with the development of symptoms makes it immunologically plausible that vaccination triggered systemic autoimmunity in these rare cases. We propose that epidemiological studies be performed to examine this potential association in more detail to quantitate the risk and identify possible genetic risk factors.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by chronic inflammation. This study sought to assess the effects of an exercise training program on cytokines and soluble TNF receptors (sTNFRs) in response to acute exercise in SLE women. Eight SLE women and 10 sex-, age-, and body mass index-comparable healthy controls (HC) participated in this study. Before and after a 12-wk aerobic exercise training program, cytokines and sTNFRs were assessed at rest and in response to single bouts of acute moderate/intense exercise. HC performed the acute exercise bouts only at baseline. After the exercise training program, there was a decrease in resting TNFR2 levels (P = 0.025) and a tend to reduction interleukin (IL)-10 levels (P = 0.093) in SLE. The resting levels of IL-6, IL-10, and TNF-α after the exercise training in SLE reached HC levels (P>0.05). In response to a single bout of acute moderate exercise, the area under the curve (AUC) of IL-10 was significantly reduced after the exercise training program in SLE (P = 0.043), and the AUC of IL-10, IL-6, TNF-α, and sTNFR1 of SLE approached control values (P>0.05). In response to a single bout of acute intense exercise, the AUC of IL-10 was significantly reduced in SLE (P = 0.015). Furthermore, the AUC of sTNFR2 tended to decrease after exercise training program in SLE (P = 0.084), but it did not reach control values (P = 0.001). An aerobic exercise training program attenuated the inflammatory milieu in SLE women, revealing a novel homeostatic immunomodulatory role of exercise in an autoimmunity condition.

AIM: Find an association between hepatitis B vaccine-related systemic lupus erythematosus and HLA. Material: A 27-year-old woman who developed a lupus nephritis after the administration of hepatitis B vaccine.

METHODS: We studied HLA antigen expression on lymphocytes and genomic haplotype. Class I-II HLA antigen typing was performed by the microlymphocytotoxicity test with the standard NIH method, and Class I-II HLA allele typing by polymerase chain reaction, using single-strand oligonucleotide dot-blot kits.

RESULTS: The serological haplotype was HLA A24/25, B18 (Bw6)/-, C-/-, DQ7/-, DR11(5)/52. The genomic haplotype was A*2403/2504, B*1825/1825, C*1207/ 1207, DRB1*1102/1132, DRB3*0202/0202, DQA1*0505/0505, DQB1*0301/0301. Then we sought for analogies with haplotypes known to be related to other systemic AID. Since we have found HLA alleles typical both of systemic lupus erythematosus and Sjogren's syndrome, the persistence of ENA-SSA positivity was highly suspicious for a possible overlap syndrome.

CONCLUSIONS: Hepatitis B vaccine can potentially trigger both the onset or the exacerbations of several autoimmune disorders, including systemic lupus erythematosus, by reduced immune complex clearance or molecular mimicry. This study represents the first report on the association between hepatitis B vaccine related systemic lupus erythematosus and HLA. Probably autoimmune reactions triggered by vaccines occur only in predisposed subjects, in which antigen presentation influenced by HLA haplotypes leads to the autoimmune cascade. More studies are needed to corroborate our hypothesis. They could disclose new pathways in the field of prevention.

To investigate the association between human papillomavirus (HPV) vaccination and autoimmune manifestations compatible with systemic lupus erythematosus (SLE) or SLE-like disease, the medical history of six women who presented with SLE or SLE-like disease following HPV immunization was collected. Data regarding type of vaccine, number of immunization, family and personal, clinical and serological features, as well as response to treatments were analyzed. In the reported cases, several common features were observed, such as personal or familial susceptibility to autoimmunity or adverse response to a prior dose of the vaccine, both of which may be associated with a higher risk of post-vaccination autoimmunity. Favorable response to immunosuppressant was observed in all patients. In the current study, a temporal association between immunization with HPV vaccine and the appearance of a spectrum of SLE-like conditions is reported. Additionally, among the patients described, several common features were observed that may enable better identification of subjects at risk. Further studies are required to assess the safety of immunization with the HPV vaccine in patients with autoimmune-rheumatic diseases or in subject at risk of autoimmunity as well as the potential beneficial effect of preventive immunosuppressants.

ABSTRACT: Skin ulcers are a dangerous and uncommon complication of vasculitis. We describe the case of a teenager suffering from Systemic Lupus Erythematosus with digital ulcer resistant to conventional therapy, treated successfully with hyperbaric oxygen therapy. The application of hyperbaric oxygen, which is used for the treatment of ischemic ulcers, is an effective and safe therapeutic option in patients with ischemic vasculitic ulcers in combination with immunosuppressive drugs. Further studies are needed to evaluate its role as primary therapy for this group of patients.

OBJECTIVE:In the present study, DNA methylation level of CD4+ T cells exposed to ultraviolet B (UVB) was investigated and its potential mechanisms were also explored.

METHODS:CD4+ T cells from 12 cases of healthy subjects and 33 cases of SLE patients were isolated and exposed to different dosages (0, 50, 100 mJ/cm) of UVB. Further, SLE patients were divided into two groups: active SLE group (22 cases, SLEDAI scores >4) and inactive SLE group (11 cases, SLEDAI scores ≤4). DNA methylation was evaluated by the Methylamp™ Global DNA Methylation Quantification Ultra Kit. The mRNA and protein expression levels of DNA methyltransferases (DNMT1 and DNMT3A) were detected by real-time PCR and western blot, respectively.

RESULTS:The levels of DNA methylation and DNMT3A mRNA in SLE patients were significantly decreased compared with those in healthy subjects at baseline. After different dosages of ultraviolet irradiation (0, 50 and 100 mJ/cm), DNA methylation levels of CD4+ T cells were all reduced in a dose-dependent manner in three subgroups. Additionally, 100 mJ/cmultraviolet irradiation in active SLE group contributed to a significant decrease of both DNA methylation and DNMT3A mRNA levels in CD4+ T cells. UVB exposure had no significant effects on expression levels of DNMT1 mRNA and protein and DNMT3A protein.

CONCLUSION:UVB decreases DNA methylation level of CD4+ T cells in SLE patients probably via inhibiting DNMT3A mRNA expression level, which needs to be further explored.

Systemic lupus erythematosus (lupus, SLE) is a chronic autoimmune disease characterized by the production of autoantibodies, which bind to antigens and are deposited within tissues to fix complement, resulting in widespread systemic inflammation. The studies presented herein are consistent with hyperpolarized, adenosine triphosphate (ATP)-deficient mitochondria being central to the disease process. These hyperpolarized mitochondria resist the depolarization required for activation-induced apoptosis. The mitochondrial ATP deficits add to this resistance to apoptosis and also reduce the macrophage energy that is needed to clear apoptotic bodies. In both cases, necrosis, the alternative pathway of cell death, results. Intracellular constituents spill into the blood and tissues, eliciting inflammatory responses directed at their removal. What results is"autoimmunity."Ultraviolet (UV)-A1 photons have the capacity to remediate this aberrancy. Exogenous exposure to low-dose, full-body, UV-A1 radiation generates singlet oxygen. Singlet oxygen has two major palliative actions in patients with lupus and the UV-A1 photons themselves have several more. Singlet oxygen depolarizes the hyperpolarized mitochondrion, triggering non-ATP-dependent apoptosis that deters necrosis. Next, singlet oxygen activates the gene encoding heme oxygenase (HO-1), a major governor of systemic homeostasis. HO-1 catalyzes the degradation of the oxidant heme into biliverdin (converted to bilirubin), Fe, and carbon monoxide (CO), the first three of these exerting powerful antioxidant effects, and in conjunction with a fourth, CO, protecting against injury to the coronary arteries, the central nervous system, and the lungs. The UV-A1 photons themselves directly attenuate disease in lupus by reducing B cell activity, preventing the suppression of cell-mediated immunity, slowing an epigenetic progression toward SLE, and ameliorating discoid and subacute cutaneous lupus. Finally, a combination of these mechanisms reduces levels of anticardiolipin antibodies and protects during lupus pregnancy. Capping all of this is that UV-A1 irradiation is an essentially innocuous, highly manageable, and comfortable therapeutic agency.

Infectious agents contribute to the environmental factors involved in the development of autoimmune diseases possibly through molecular mimicry mechanisms. Hence, it is feasible that vaccinations may also contribute to the mosaic of autoimmunity. Evidence for the association of vaccinations and the development of these diseases is presented in this review. Infrequently reported post-vaccination autoimmune diseases include systemic lupus erythematosus, rheumatoid arthritis, inflammatory myopathies, multiple sclerosis, Guillain-Barré syndrome, and vasculitis. In addition, we will discuss macrophagic myofasciitis, aluminum containing vaccines, and the recent evidence for autoimmunity following the use of human papillomavirus vaccine.