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In the course of investigating anti-DNA autoantibodies, we examined IgM and IgG antibodies to poly-G and other oligonucleotides in the sera of healthy persons and those diagnosed with systemic lupus erythematosus (SLE), scleroderma (SSc), or pemphigus vulgaris (PV); we used an antigen microarray and informatic analysis. We now report that all of the 135 humans studied, irrespective of health or autoimmune disease, manifested relatively high amounts of IgG antibodies binding to the 20-mer G oligonucleotide (G20); no participants entirely lacked this reactivity. IgG antibodies to homo-nucleotides A20, C20 or T20 were present only in the sera of SLE patients who were positive for antibodies to dsDNA. The prevalence of anti-G20 antibodies led us to survey human, mouse and Drosophila melanogaster (fruit fly) genomes for runs of T20 and G20 or more: runs of T20 appear > 170,000 times compared with only 93 runs of G20 or more in the human genome; of these runs, 40 were close to brain-associated genes. Mouse and fruit fly genomes showed significantly lower T20/G20 ratios than did human genomes. Moreover, sera from both healthy and SLE mice contained relatively little or no anti-G20 antibodies; so natural anti-G20 antibodies appear to be characteristic of humans. These unexpected observations invite investigation of the immune functions of anti-G20 antibodies in human health and disease and of runs of G20 in the human genome., (© 2015 John Wiley & Sons Ltd.)

The role of vitamin D as an immune modulator has been emphasized in recent years, and low levels of the hormone were observed in several autoimmune diseases including multiple sclerosis and systemic lupus erythematosus. Vitamin D mediates its effect though binding to vitamin D receptor (VDR), and activation of VDR-responsive genes. While VDR gene polymorphism was found to associate with autoimmune thyroid diseases (AITDs), few studies examined levels of vitamin D in these patients and those that did yielded conflicting results. We therefore undertook to evaluate the levels of vitamin D in patients with AITDs compared to patients with non-AITDs and healthy controls. Serum vitamin D (25-OH) levels were measured in 50 patients with AITDs, 42 patients with non-AITDs and 98 healthy subjects, utilizing the LIAISON chemiluminescence immunoassay (DiaSorin, Saluggia, Italy). Vitamin D deficiency was designated at levels lower than 10 ng/ml. Antithyroid antibodies, thyroid functions and demographic parameters were evaluated in all patients. The prevalence of vitamin D deficiency was significantly higher in patients with AITDs compared with healthy individuals (72% versus 30.6%; P<0.001), as well as in patients with Hashimoto's thyroiditis compared to patients with non-AITDs (79% versus 52%; P<0.05). Vitamin D deficiency also correlated to the presence of antithyroid antibodies (P=0.01) and abnormal thyroid function tests (P=0.059). Significantly low levels of vitamin D were documented in patients with AITDs that were related to the presence of anti thyroid antibodies and abnormal thyroid function tests, suggesting the involvement of vitamin D in the pathogenesis of AITDs and the advisability of supplementation.

Summary: Patients with systemic lupus erythematosus (SLE) produce antibodies to many different self-antigens. Here, we investigated antibodies in SLE sera using an antigen microarray containing many hundreds of antigens, mostly self-antigens. The aim was to detect sets of antibody reactivities characteristic of SLE patients in each of various clinical states--SLE patients with acute lupus nephritis, SLE patients in renal remission, and SLE patients who had never had renal involvement. The analysis produced two novel findings: (i) an SLE antibody profile persists independently of disease activity and despite long-term clinical remission, and (ii) this SLE antibody profile includes increases in four specific immunoglobulin G (IgG) reactivities to double-stranded DNA (dsDNA), single-stranded DNA (ssDNA), Epstein-Barr virus (EBV) and hyaluronic acid; the profile also includes decreases in specific IgM reactivities to myeloperoxidase (MPO), CD99, collagen III, insulin-like growth factor binding protein 1 (IGFBP1) and cardiolipin. The reactivities together showed high sensitivity (> 93%) and high specificity for SLE (> 88%). A healthy control subject who had the SLE antibody profile was later found to develop clinical SLE. The present study did not detect antibody reactivities that differentiated among the various subgroups of SLE subjects with statistical significance. Thus, SLE is characterized by an enduring antibody profile irrespective of clinical state. The association of SLE with decreased IgM natural autoantibodies suggests that these autoantibodies might enhance resistance to SLE.

In this study we assess the presence of antibodies against infectious agents as well as for a variety of autoantibodies in an attempt to establish associations between various vasculitides and infections in order to shed light on the etiopathogenesis of these diseases and perhaps implicate a potential cure. Sera from patients with Wegener's granulomatosis (WG), polyarteritis nodosa, microscopic polyangiitis, Churg Strauss, and giant cell arteritis were compared to healthy control sera. Serum samples were assessed, using the Bio-Rad BioPlex 2200, for the presence of Toxoplama gondii, cytomegalovirus (CMV), Epstein-Barr virus (EBV), Treponema pallidum, and Saccharomyces cerevisiae. Hepatitis B virus (HBV), hepatitis C virus (HCV), and anti-Helicobacter pylori antibodies were assessed by ELISA. In addition, sera were tested for a panel of antibodies associated with thrombophilia as well as various autoantibodies. The prevalence of antibodies toward HCV and H. pylori was significantly higher among patients with WG. IgG antibodies toward T. gondii and IgM antibodies toward CMV were significantly more common among WG patients than among controls. WG patients exhibited more antibodies toward EBV viral capsid antigen IgG and EBV early antigen IgG compared to sera from healthy controls. In WG, positive associations were disclosed between CMV IgG antibodies and the presence of gastrointestinal manifestations and renal involvement, and there was a higher Birmingham vasculitis activity score in association with elevated titers of EBV viral capsid antigen IgG antibodies. Otorhinolaryngeal manifestations were more common in those with positive IgG antibodies for EBV early antigen. Our results unveil novel associations between WG and various infectious agents, including HCV, H. pylori, T. gondii, CMV, and EBV. In addition to putative roles in initiation and exacerbation of the vasculitic process, it seems that these infectious agents also modulate the clinical phenotype of the disease.

The aim of this study was to reevaluate the role of infection in inflammatory bowel disease (IBD). Sera from 119 patients with IBD [80 with Crohn's disease (CD); 39 with ulcerative colitis] and 98 healthy controls were assessed using the Bio-Rad BioPlex 2200 for the presence of Toxoplasma gondii, cytomegalovirus, Epstein-Barr virus, Treponema pallidum, and Saccharomyces cerevisiae. Hepatitis B virus, hepatitis C virus (HCV), and anti-Helicobacter pylori antibodies were assessed by ELISA. In addition, sera were tested for a panel of antibodies associated with thrombophilia as well as various autoantibodies. Titers of antibodies toward HCV and T. gondii, and S. cerevisiae were higher in IBD patients than in controls, while the H. pylori autoantibodies were less prevalent among the patient population. Several thrombophilia-associated antibodies were more common in CD patients, and a single patient had a thromboembolic event. Our results show an excess of anti-HCV and anti-T. gondii antibodies among patients with IBD compared to healthy controls. Whereas the former may be the result of immunosuppression from the inflammatory disease itself or from the medications used to treat it, the latter association suggests that T. gondii is involved in the etiopathogenesis of IBD, and especially CD, in humans, as has been shown in the murine model. However, our findings also reiterate the positive association between CD and anti-S. cerevisiae antibodies as well as the negative association with H. pylori infections. These, in turn, lend indirect support to the "hygiene hypothesis" in IBD as well as the newly proposed role of commensal bacteria in the initiation of the disease process.

The nervous system may be involved in up to 30% of patients with Sjogren's syndrome (SS). We describe three patients with Sjogren's syndrome and a concomitant parkinsonian syndrome. Elevated titers of anti-beta2-glycoprotein I IgG were found in the serum of all three patients. This autoantibody is strongly associated with anticardiolipin (aCL) antibodies, antiphospholipid syndrome (APS), and thromboembolic phenomena, but its role in the pathogenesis of the parkinsonian disorder in SS is unclear. These patients may present a subtype of SS patients in which the presence of aCL antibodies is associated with central nervous system involvement predominantly in the basal ganglia.

Systemic lupus erythematosus (SLE) is a multi-systemic autoimmune disease leading to immunological aberrations and excessive multiple autoantibody production. The aim of this study was to investigate the prevalence of multiple autoantibodies in SLE patients utilizing the multiplex system method. We analyzed the presence of elevated titers of anti-Ro, anti-La, anti-RNP, anti-Sm, anti-Jo1, anti-centromere, anti-Scl-70, anti-histone, and anti-dsDNA antibodies in 199 serum samples (113 SLE patients, 86 healthy donors). We compared the type, level and number of autoantibodies and the correlation between the autoantibody profile and disease severity utilizing the SLEDAI score. Elevated titers of at least one autoantibody were detected in 48% of 42 SLE patients. Elevated titers of anti-Ro antibodies were most commonly detected. The distribution of specific autoantibodies was: anti-Ro- 23.8%, anti-dsDNA- 19%, antihistone- 19%, anti-RNP- 14.2%, anti-La antibodies- 11.9%, anti-Sm- 7.1%, anti-Scl 70-4.7%, and anti-centromere- 2.4%. Utilizing ROC analysis, the sensitivity and specificity of anti-DNA antibodies at a cutoff value of 34 IU/ml were 87.1% and 79.4% respectively. Elevated titers of anti-Jo1 antibody were not detected. There was a correlation with the titer of anti-Ro antibodies and disease activity by the SLEDAI score. Seven patients harbored one autoantibody only, 15 patients harbored 2-3 autoantibodies, 3 patients harbored 4-5 autoantibodies, and one patient harbored 6 autoantibodies. A correlation between the number of autoantibodies per patient and disease severity was found. One patient with a multitude of autoantibodies had severe lupus and a myriad of clinical manifestations. In conclusion, the multiplex system is specific and sensitive, provides an autoantibody profile in a single test, and may be useful as a diagnostic test for SLE. Elevated anti-Ro antibodies are associated with severe disease. An autoantibody load may be indicative of more severe disease.

Systemic lupus erythematosus ( SLE) is an autoimmune disease that can attack many different body organs; the triggering event is unknown. SLE has been associated with more than 100 different autoantibody reactivities - anti-ds DNA is prominent. Nevertheless, autoantibodies to ds DNA occur in only two-thirds of SLE patients. We previously reported the use of an antigen microarray to characterize SLE serology. We now report the results of an expanded study of serology in SLE patients and scleroderma ( SSc) patients compared with healthy controls. The analysis validated and extended previous findings: two-thirds of SLE patients reacted to a large spectrum of self-molecules that overlapped with their reactivity to ds DNA; moreover, some SLE patients manifested a deficiency of natural IgM autoantibodies. Most significant was the finding that many SLE patients who were negative for autoantibodies to ds DNA manifested abnormal antibody responses to Epstein-Barr virus ( EBV): these subjects made IgG antibodies to EBV antigens to which healthy subjects did not respond or they failed to make antibodies to EBV antigens to which healthy subjects did respond. This observation suggests that SLE may be associated with a defective immune response to EBV. The SSc patients shared many of these serological abnormalities with SLE patients, but differed from them in increased IgG autoantibodies to topoisomerase and centromere B; 84% of SLE patients and 58% of SSc patients could be detected by their abnormal antibodies to EBV. Hence an aberrant immune response to a ubiquitous viral infection such as EBV might set the stage for an autoimmune disease. [ABSTRACT FROM AUTHOR]

Background: Autoimmune vasculitides cannot always be controlled by steroids and immunosuppressive drugs. Intravenous immunoglobulin (IVIg) treatment was found beneficial in several vasculitides including systemic and organ–specific diseases. In this article we tested whether the beneficial clinical response of IVIg treatment in vasculitides was accompanied by a decrease in vasculitis–associated autoantibody levels. Methods: Ten patients diagnosed as having vasculitis were treated with high–dose (2 g/kg) IVIg monthly, in a 5–day schedule. In all the patients, other therapeutic measures failed to control disease progression prior to IVIg treatment. Each patient received between 1 and 6 treatment courses. All patients were evaluated for the levels of 5 autoantibodies (Abs) related to vasculitis before and after each treatment course. Results: In 6 out of the 10 patients, a beneficial clinical response followed IVIg treatment. Moreover, no treatment–related adverse effects were observed in any of the patients. Anti–myeloperoxidase antibodies and cytoplasmic–antineutrophil cytoplasmic antibodies levels decreased concomitantly with the clinical improvement observed in the patients with Churg–Strauss vasculitis and Wegener’s granulomatosis, respectively. Levels of cytoplasmic–antineutrophil cytoplasmic antibodies (ANCA) with specificity for bacteridial/permeability–increasing protein and human lysosomal–associated membrane protein increased after each treatment course, but returned to normal values before the following one. Conclusions: When other therapeutic measures, such as immunosuppressive therapy, fails to control disease manifestations in patients with vasculitides, IVIg is a possible effective intervention method with a high response rate. IVIg probably exerted its effects on disease progression via different mechanisms. Among these mechanisms, a decrease in relevant Ab levels is often found (probably by anti–idiotypes in IVIg), and thus ANCA levels are expected to associate with disease activity. [ABSTRACT FROM AUTHOR]

Endothelial dysfunction is considered an important marker in atherosclerosis, having a prognostic value. Antiphospholipid antibodies are considered prothrombotic and have recently been reported to be associated also with atherosclerosis. This study was conducted to investigate a possible association of endothelial dysfunction with various antiphospholipid autoantibodies in healthy subjects and patients with cardiovascular disease. In a single-center, prospective study, 2 groups were included. The study group included patients with cardiovascular diseases (coronary disease and/or cerebrovascular disease) and healthy subjects without apparent heart disease who were referred to the endothelial function laboratory for the assessment of endothelial function. Flow-mediated dilatation, which indicates endothelial function, and nitroglycerin-mediated vasodilatation, which indicates smooth-muscle function, were measured. The 2 groups were evaluated for autoantibodies, including anticardiolipin (aCL; immunoglobulin G [IgG], immunoglobulin M [IgM], and immunoglobulin A [IgA]), antinuclear antibody, anti–β2-glycoprotein I (IgG, IgM, and IgA), and oxidized low-density lipoprotein. One hundred seven subjects were included in the study: 45 patients (42%) and 62 healthy controls (58%). Flow-mediated dilatation was significantly lower in patients compared with healthy controls (8.0 ± 9.5% vs 8.0 ± 13.5%, p = 0.012). In addition, nitroglycerin-mediated vasodilatation was nonsignificantly lower in patients than in healthy controls (8.0 ± 13.4% vs 11.0 ± 16.7%, p = 0.084). The mean levels of anti–β2-glycoprotein I (IgG, IgM, and IgA), aCL (IgM and IgA), antinuclear antibody, and oxidized low-density lipoprotein were not different between groups. However, the mean level of IgG aCL was significantly higher in patients than in healthy controls. In conclusion, in accordance with previous reports of an association between aCL and atherosclerosis, patients with cardiovascular disease had endothelial dysfunction and elevated levels of aCL. [Copyright &y& Elsevier]