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Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with multi-organ inflammation, linked to loss of immune tolerance to self-antigens and the production of a diversity of autoantibodies, with a negative impact on the patients' quality of life. Regulatory T cells have been reported as deficient in number and function in SLE patients. However, some authors also described an enrichment of this cell type. The hypothesis that certain forms of autoimmunity may result from a conversion of Treg cells into a Th17 cell phenotype has been suggested by some studies. In fact, in SLE patients' sera, the IL-17 levels were observed as abnormally high when compared with healthy individuals. Environmental factors, such as vitamin D, that is considered a potential anti-inflammatory agent, combined with genetic and hormonal characteristics have been associated with SLE phenotype and with disease progression. The aim of this study was to evaluate the effect of vitamin D supplementation on FoxP3 expression and IL-17A-producing T cells, through FoxP3 + /IL-17A ratio. Additionally, disease evolution, serum vitamin D levels, serum autoantibodies levels and calcium metabolism (to assure safety) were also studied. We assessed 24 phenotypically well-characterized SLE patients. All patients were screened before vitamin D supplementation and 3 and 6 months after the beginning of this treatment. Peripheral blood lymphocyte's subsets were analysed by flow cytometry. Serum 25(OH)D levels significantly increased under vitamin D supplementation (p = 0.001). The FoxP3 + /IL-17A ratio in SLE patients after 6 months of vitamin D supplementation was higher than that in the baseline (p < 0.001). In conclusion, this study demonstrated that vitamin D supplementation provided favourable, immunological and clinical impact on SLE.

Scleroderma (SSc) is a rare and heterogeneous immune-mediated disease involving the connective tissue and microvasculature whose pathogenesis remains unclear. Data concerning T and natural killer (NK) cell abnormalities and cytokine levels in the peripheral blood (PB) from patients with SSc are scarce, and the results are contradictory. The present study aimed to analyze the changes of T lymphocytes, NK cells, and T helper (Th)-related cytokines in the PB of patients with SSc in comparison to healthy individuals and its relation to disease subtype and stage, organ involvement, and nailfold capillaroscopic changes. A non-random convenience sample of 57 scleroderma patients was utilized. Fifty-five out of the 57 patients studied were women (97 %); 10 patients presented pre-scleroderma (pre-SSc) and 47 SSc: 34 limited cutaneous SSc (lcSSc) and 13 diffuse cutaneous SSc (dcSSc). Patients with SSc were classified in early (n = 7), intermediate (n = 10), and late (n = 30) disease. Blood samples were analyzed by flow cytometry for total T cells, CD4+ and CD8+ T cell subsets, total NK cells, and CD56+low and CD56+high NK cell subsets. T cells were further analyzed for the expression of the CD56 adhesion molecule and activation-related markers (HLA-DR, CD45RO). In addition, the serum levels of Th1-, Th2-, and Th17-related cytokines were measured by flow cytometry. Twenty-five healthy individuals recruited from the blood bank were used as controls. Patients had lower numbers of total lymphocytes and T cells comparing to healthy controls. Both CD4+ and CD8+ T cells were decreased, but differences were statistically significant only for CD8+ and CD8+ CD45RO+ T cells. These alterations were seen in patients with SSc but not in patients with pre-SSc, and, in general, they were more pronounced in patients with dcSSc than in patients with lcSSc, in patients with vascular involvement than in those without, as well as in patients having active and late nailfold capillaroscopic patterns. CD56+ T cells were also decreased in SSc patients, especially in those with active/late capillaroscopic patterns or with severe lung disease. Diminished numbers of circulating NK cells were also observed in patients with lcSSc and in those with early disease. No statistically significant changes were found in serum cytokine levels, as compared with controls. Patients with SSc had major alterations in circulating CD8+ and CD56+ T cells, as well as in NK cells, suggesting that these cells may play a relevant role in SSc pathogenesis, probably operating at different phases and/or at different organs. In addition, the serum levels of Th1, Th2, and Th17 cytokines did not provide useful information for evaluating T cell polarization in SSc.

Raynaud's phenomenon and digital ulcers (DUs) are frequent among systemic sclerosis (SSc) patients. Our aim was to investigate the diagnostic and predictive value for DU of endothelial dysfunction biomarkers (flow-mediated dilatation (FMD), serum levels of endothelin-1 (ET-1), and ADMA), angiogenic/angiostatic biomarkers (vascular endothelial growth factor (VEGF), endoglin, and endostatin), and nailfold videocapillaroscopy (NVC). We compared our results with a literature review. In a cohort study of 77 SSc patients, we followed two groups of patients: (i) naïve DU patients (39) and (ii) active DU at baseline (38 patients) for 3 years. Telangiectasia (p < 0.001) and diffuse disease subset (p = 0.001) were significantly more frequent in patients with active DU at enrolment. Additionally, NVC late scleroderma pattern (AUC 0.846, 95%CI 0.760-0.932), lower values of FMD (AUC 0.754, 95%CI 0.643-0.864), increased serum levels of ET-1 (AUC 0.758, 95%CI 0.649-0.866), ADMA (AUC 0.634, 95%CI 0.511-0.757), and endoglin as well as low VEGF serum levels (AUC 0.705, 95%CI 0.579-0.830) were significantly associated to new DU events in the 3-year follow-up. Cox regression analysis showed that FMD > 9.41 % (HR 0.37, 95%CI 0.14-0.99); ET-1 >11.85 pmol/L (HR 3.81, 95%CI 1.41-10.26) and late NVC pattern (HR 2.29, 95%CI 0.97-5.38) were independent predictors of DU recurrence. When estimating the probability of occurrence of first DU in naïve DU patients, only late NVC pattern (HR 12.66, 95%CI 2.06-77.89) was an independent predictor factor. In conclusion, late scleroderma patterns in NVC are the best independent predictors of SSc patients who are at risk of developing DU. Endothelial dysfunction assessed by FMD and ET-1 was also found to be an independent predictor of DU recurrence in a 3-year follow-up.

Manganese (Mn) is an essential element and it acts as a cofactor for a number of enzymatic reactions, including those involved in amino acid, lipid, protein, and carbohydrate metabolism. Excessive exposure to Mn can lead to poisoning, characterized by psychiatric disturbances and an extrapyramidal disorder. Mn-induced neuronal degeneration is associated with alterations in amino acids metabolism. In the present study, we analyzed whole rat brain amino acid content subsequent to four or eight intraperitoneal injections, with 25 mg MnCl₂/kg/day, at 48-h intervals. We noted a significant increase in glycine brain levels after four or eight Mn injections (p < 0.05 and p < 0.01, respectively) and arginine also after four or eight injections (p < 0.001). Significant increases were also noted in brain proline (p < 0.01), cysteine (p < 0.05), phenylalanine (p < 0.01), and tyrosine (p < 0.01) levels after eight Mn injections vs. the control group. These findings suggest that Mn-induced alterations in amino acid levels secondary to Mn affect the neurochemical milieu.

Progressive multifocal leukoencephalopathy (PML) is a rare opportunistic infection caused by the reactivation of JC virus and occurs in patients with severe primary or secondary immunosuppression. Recently, PML is becoming relevant in autoimmune disorders, particularly in patients treated with biologic agents. However, systemic lupus erythematosus (SLE) appears to be associated with susceptibility to PML that cannot be entirely explained by the immunosuppressive therapy. The authors present two patients with the diagnosis of SLE and PML: One had a heavy immunosuppressive therapy history, and the other had never experienced biologic or cytotoxic therapeutics. Both patients had a profound T-CD4+ lymphopenia during their clinical history. These two cases emphasize the importance of CD4+ lymphopenia in SLE patients with and without immunosuppressors regarding opportunistic infections.

Systemic lupus erythematosus (SLE) is mainly a disease of fertile women and the coexistence of pregnancy is by no means a rare event. How SLE and its treatment affects pregnancy outcome is still a matter of debate. Assessment of the reciprocal clinical impact of SLE and pregnancy was investigated in a cohort study. We reviewed the clinical features, treatment, and outcomes of 43 pregnant SLE patients with 51 pregnancies followed from 1993 to 2007 at a tertiary university hospital. The age of patients was 28.7 +/- 5.4 years and SLE was diagnosed at age of 23.0 +/- 6.1 years. Previous manifestations of SLE included lupus nephritis (14 patients) and secondary antiphospholipid syndrome (11 patients). Thirty-five pregnant patients (69%) were in remission for more than 6 months at the onset of pregnancy. Patients were being treated with low doses of prednisone (29), hydroxychloroquine (20), azathioprine (five), acetylsalicylic acid (51), and low molecular weight heparin (13). Sixteen pregnancy-associated flares were documented, mainly during the second trimester (42%) and also in the following year after delivery (25%). Renal involvement was found in 11 cases (68%). Spontaneous abortion occurred in 6%, 16% had premature deliveries, and 74% were delivered at term. No cases of maternal mortality occurred. No cases of fetal malformation were recorded. There was one intrauterine fetal death and one neonatal death at 24 gestational weeks. Pregnant women with SLE are high risk patients, but we had a 90% success rate in our cohort. A control disease activity strategy to target clinical remission is essential.