Vitiligo is a chronic disease characterized by the dysfunction or destruction of melanocytes with secondary depigmentation. The aim of the present study was to determine the prevalence of vitiligo associated with autoimmune rheumatic diseases. The clinical records from a 10-year database of patients with rheumatic diseases and associated vitiligo was analysed, with one group of patients having autoimmune rheumatic disease and another non-autoimmune rheumatic disease. Available serum samples were used to assess the anti-melanocyte antibodies. A total of 5,251 individual clinical files were archived in the last 10 years, and these patients underwent multiple rheumatology consultations, with 0.3% of the group presenting with vitiligo. The prevalence of vitiligo in the autoimmune rheumatic disease group was 0.672%, which was mainly associated with lupus and arthritis. However, patients with more than one autoimmune disease had an increased relative risk to develop vitiligo, and anti-melanocyte antibodies were positive in 92% of these patients. By contrast, the prevalence was 0.082% in the group that lacked autoimmune rheumatic disease and had negative autoantibodies. In conclusion, the association between vitiligo and autoimmune rheumatic diseases was relatively low. However, the relative risk increased when there were other autoimmune comorbidities, such as thyroiditis or celiac disease. Therefore, the presence of multiple autoimmune syndromes should be suspected.

The present study investigated posttranslational reactions in the salivary glands of patients with Sjögren's syndrome. We analysed the biopsies of primary Sjögren's patients using immunohistochemistry and a tag-purified anticyclic citrullinated protein (CCP) antibody to detect citrullinated peptides, and the presence of peptidylarginine deiminase 2 (PAD2) was assessed simultaneously. The present work demonstrated the weak presence of the PAD2 enzyme in some normal salivary glands, although PAD2 expression was increased considerably in Sjögren's patients. The presence of citrullinated proteins was also detected in the salivary tissues of Sjögren's patients, which strongly supports the in situ posttranslational modification of proteins in this setting. Furthermore, the mutual expression of CCP and PAD2 suggests that this posttranslational modification is enzyme dependent. In conclusion, patients with Sjögren's syndrome expressed the catalytic machinery to produce posttranslational reactions that may result in autoantigen triggering.

Autoimmune nephritis triggered by metallic ions was assessed in a Long-Evans rat model. The parameters evaluated included antinuclear autoantibody production, kidney damage mediated by immune complexes detected by immunofluorescence, and renal function tested by retention of nitrogen waste products and proteinuria. To accomplish our goal, the animals were treated with the following ionic metals: HgCl2, CuSO4, AgNO3, and Pb(NO3)2. A group without ionic metals was used as the control. The results of the present investigation demonstrated that metallic ions triggered antinuclear antibody production in 60% of animals, some of them with anti-DNA specificity. Furthermore, all animals treated with heavy metals developed toxic glomerulonephritis with immune complex deposition along the mesangium and membranes. These phenomena were accompanied by proteinuria and increased concentrations of urea. Based on these results, we conclude that metallic ions may induce experimental autoimmune nephritis.

Concentrations of circulating fibronectin were studied in plasma of 22 patients with acquired immunodeficiency syndrome and 24 healthy blood donors. There were significant differences between the plasma fibronectin values of the patient population with AIDS (mean 2 SD = 206 +/- 86 mg/l) and of the control group (mean +/- 2 SD = 297 +/- 92 mg/l). AIDS patients with visceral leishmaniasis showed a significant diminution of plasma fibronectin concentration (mean +/- 2 SD = 132 +/- 31 mg/l). A significant increase in plasma fibronectin concentrations was noted after 14 days of treatment with antimony (mean 2 SD = 239 +/- 67 mg/l). These results suggest that the measurement of fibronectin concentrations in patients with AIDS especially with concurrent infection, contributes to diagnosis. A significant decrease in plasma fibronectin concentrations was observed in patients with AIDS and visceral leishmaniasis.

The goal of the present study was to determine whether peptidylarginine deiminase PAD2 and PAD4 enzymes are present in Balb/c mouse salivary glands and whether they are able to citrullinate Ro and La ribonucleoproteins. Salivary glands from Balb/c mice were cultured in DMEM and supplemented with one of the following stimulants: ATP, LPS, TNF, IFNγ, or IL-6. A control group without stimulant was also evaluated. PAD2, PAD4, citrullinated peptides, Ro60, and La were detected by immunohistochemistry and double immunofluorescence. PAD2 and PAD4 mRNAs and protein expression were detected by qPCR and Western blot analysis. PAD activity was assessed using an antigen capture enzyme-linked immunosorbent assay. LPS, ATP, and TNF triggered PAD2 and PAD4 expression; in contrast, no expression was detected in the control group (p < 0.001). PAD transcription slightly increased in response to stimulation. Additionally, PAD2/4 activity modified the arginine residues of a reporter protein (fibrinogen) in vitro. PADs citrullinated Ro60 and La ribonucleoproteins in vivo. Molecular stimulants induced apoptosis in ductal cells and the externalization of Ro60 and La ribonucleoproteins onto apoptotic membranes. PAD enzymes citrullinate Ro and La ribonucleoproteins, and this experimental approach may facilitate our understanding of the role of posttranslational modifications in the pathophysiology of Sjögren's syndrome.

Sjögren's syndrome is an autoimmune epithelitis of salivary and lachrymal glands that results in Sicca syndrome. Citrulline is synthesised by the conversion of ornithine to arginine during urea formation, exists as free citrulline produced by NOS enzymes, and another form produced by post‐translational modification of proteins at arginine residues by peptidylarginine deiminases (PADs), which is important in autoimmunity. We investigate post‐translational reactions in salivary gland biopsies from 24 patients with primary Sjögren's syndrome and 24 controls using immunohistochemistry and a tag‐purified anti‐cyclic citrullinated protein CCP antibody to detect citrullinated peptides, PAD2 also was assessed. The present work demonstrated the weak presence of the PAD2 in some normal salivary ducts (10%), although PAD2 expression was increased considerably in Sjögren's patients. The presence of citrullinated proteins in the salivary tissues of Sjögren's patients strongly supports the in situ post‐translational modification of proteins in this setting. The mutual expression of CCP and PAD2 (70%) suggests that this post‐translational modification is enzyme‐dependent. In conclusion, patients with Sjögren's syndrome expressed the catalytic machinery to produce post‐translational reactions that may result in auto‐antigen triggering.Grant: P/PIFI 2011–32MSU0017H‐06–01