Multiparametric autoantibody analysis: a new paradigm for the diagnosis of connective tissue diseases.

BACKGROUND: In patients affected by connective tissue diseases (CTDs), the identification of wide autoantibody profiles may prove useful in early diagnosis, in the evaluation of prognosis (risk stratification), and in predicting response to therapy. The aim of the present study was to evaluate the utility of multiparametric autoantibody analysis performed by a new fully automated particle-based multi-analyte technology (PMAT) digital system in a large multicenter cohort of CTD patients and controls. METHODS: Serum samples from 787 patients with CTD (166 systemic lupus erythematosus; 133 systemic sclerosis; 279 Sjögren's syndrome; 106 idiopathic inflammatory myopathies; 103 undifferentiated CTD), 339 patients with other disorders (disease controls) (118 infectious diseases, 110 organ-specific autoimmune diseases, 111 other rheumatic diseases), and 121 healthy subjects were collected in 13 rheumatologic centers of the FIRMA group. Sera were analyzed with the Aptiva-PMAT instrument (Inova Diagnostics) for a panel of 29 autoantibodies. RESULTS: Multiparametric logistic regression showed that enlarged antibody profiles have a higher diagnostic efficiency than that of individual antibodies or of antibodies that constitute classification criteria for a given disease and that probability of disease increases with multiple positive autoantibodies. CONCLUSIONS: This is the first study that analyzes the clinical and diagnostic impact of autoantibody profiling in CTD. The results obtained with the new Aptiva-PMAT method may open interesting perspectives in the diagnosis and sub-classification of patients with autoimmune rheumatic diseases.

Does vitamin D play a role in autoimmune endocrine disorders? A proof of concept.

In the last few years, more attention has been given to the "non-calcemic" effect of vitamin D. Several observational studies and meta-analyses demonstrated an association between circulating levels of vitamin D and outcome of many common diseases, including endocrine diseases, chronic diseases, cancer progression, and autoimmune diseases. In particular, cells of the immune system (B cells, T cells, and antigen presenting cells), due to the expression of 1α-hydroxylase (CYP27B1), are able to synthesize the active metabolite of vitamin D, which shows immunomodulatory properties. Moreover, the expression of the vitamin D receptor (VDR) in these cells suggests a local action of vitamin D in the immune response. These findings are supported by the correlation between the polymorphisms of the VDR or the CYP27B1 gene and the pathogenesis of several autoimmune diseases. Currently, the optimal plasma 25-hydroxyvitamin D concentration that is necessary to prevent or treat autoimmune diseases is still under debate. However, experimental studies in humans have suggested beneficial effects of vitamin D supplementation in reducing the severity of disease activity. In this review, we summarize the evidence regarding the role of vitamin D in the pathogenesis of autoimmune endocrine diseases, including type 1 diabetes mellitus, Addison's disease, Hashimoto's thyroiditis, Graves' disease and autoimmune polyendocrine syndromes. Furthermore, we discuss the supplementation with vitamin D to prevent or treat autoimmune diseases.

Anti-brain autoantibodies in the serum of schizophrenic patients: a case-control study.

Schizophrenia is considered a neurodevelopmental disorder with a multifactorial pathogenesis where autoimmune factors may play a significant role. The aim of this study was to verify the presence of anti-brain autoantibodies in the serum of schizophrenic patients compared to healthy controls. Autoantibodies against brain were detected by the immunofluorescence method, utilizing sections of rat hippocampus and hypothalamus and of monkey cerebellum. Three different fluorescence patterns were observed, staining the nucleus-cytoplasm of neurons, the neuroendothelial of blood vessel and the neurofilaments. Search for other organ-specific and non organ-specific autoantibodies was performed in all sera by indirect immunofluorescence method, enzyme linked immunosorbent assay and chemiluminescence immunoassay. Results showed a significant association between schizophrenia and anti-brain autoantibodies against the neuroendothelium of blood vessel in hypothalamus, hippocampus and cerebellum; a significant nuclear and cytoplasmic staining of neurons was assessed only for the hippocampus. No other significant association was found, except between schizophrenia and anti-nuclear autoantibodies on HEp-2 cells. In conclusion, these results support the hypothesis of a significant association between schizophrenia and circulating anti-brain autoantibodies, suggesting a diffuse reactivity against the neuroendothelium of blood vessel and highlighting a nuclear and cytoplasmic staining of the neurons of hippocampus.

Can supplementation with vitamin D reduce the risk or modify the course of autoimmune diseases? A systematic review of the literature.

OBJECTIVE: To evaluate whether vitamin D levels are related to the risk of developing autoimmune diseases and whether supplementation with vitamin D can modify the course of the diseases. METHODS: We reviewed the most relevant papers published from January 1973 to October 2011, using Medline and EMBASE and the search terms "vitamin D"; "autoimmune disease"; "autoimmunity"; "rheumatoid arthritis"; "systemic lupus erythematosus"; "scleroderma"; "systemic sclerosis"; "type 1 diabetes"; "multiple sclerosis"; and "undifferentiated connective tissue disease". We selected studies on the environmental, genetic and epidemiologic association of vitamin D with autoimmune diseases. Using the strategy described, we identified 1268 articles. 331 articles were eliminated on the basis of the title and another 703 on the basis of the abstract, since they were considered irrelevant for the purposes of the study. Full-text examination was performed on the remaining 234 studies, and a further 15 studies were excluded from the review, since the results had been confirmed or superseded by more recent research. Finally, a systematic review was conducted on 219 articles concerning cross-sectional data on: vitamin D levels and autoimmune diseases; interventional data on vitamin D supplementation in autoimmune diseases; prospective data linking vitamin D level or intake to autoimmune disease risk. RESULTS: Physiopathology studies confirm that hypovitaminosis D, in genetically predisposed subjects, can impair self tolerance by compromising the regulation of dendritic cells, of regulatory T-lymphocytes and of Th1 cells. Cross-sectional studies show that levels of vitamin D <30 ng/mL are present in a significant percentage, not only in patients with autoimmune disease, but also in healthy subjects (30-77%), and link profound deficiency (<10 ng/mL) with aggravation of symptomatology, while genetic studies associate polymorphism of vitamin D receptors to various autoimmune diseases. Among experimental studies on humans, only those on type-1 diabetes prove that the risks are significantly reduced in infants treated with vitamin D after the 7th month (OR 0.71, 95% CI, 0.60 to 0.84) and that a dose-response effect exists. CONCLUSIONS: Basic, genetic, and epidemiological studies indicate a potential role of vitamin D in the prevention of autoimmune diseases, but randomized and controlled trials are necessary to establish the clinical efficacy of vitamin D supplementation in ill or at-risk subjects.