Objective. To assess the functional status of the IL-15/IL-15Rα cytokine system in different leucocyte subsets from patients with systemic lupus erythematosus (SLE). Methods. Eighteen patients with SLE (10 with inactive and eight with active disease) and 14 healthy individuals were studied. Serum levels and in vitro production of IL-15 were determined. In addition, the expression of IL-15 receptor α (IL-15Rα) and membrane-bound IL-15 was assessed and the in vitro effects of IL-15 on CD69 and CD64 expression, interferon-γ and TNF-α synthesis, respiratory burst induction and apoptosis were studied. Results. Serum levels of IL-15 were significantly increased in inactive and active patients with SLE. Accordingly, the in vitro synthesis and release of IL-15 by monocytes in response to IFN-γ+lipopolysaccharide was significantly enhanced in SLE patients with active disease, as was the percentage of membrane-bound IL-15⁺ monocytes. On the other hand, enhanced basal expression of IL-15Rα was detected in leucocytes from SLE patients, with defective induction upon stimulation with phytohaemagglutinin or phorbol myristate acetate/ionomycin. Furthermore, diminished induction of CD69 expression and interferon-γ and TNF-α synthesis by recombinant human IL-15 was detected in peripheral blood mononuclear cells from SLE, and there was defective induction of CD64 and priming for respiratory burst in neutrophils. The anti-apoptotic effect of IL-15 was diminished in leucocytes from SLE patients. Conclusion. Our data indicate that there is enhanced synthesis of IL-15 by immune cells from SLE patients, with a poor response to this cytokine by different leucocyte subsets. This abnormal function of IL-15/IL-15Rα may contribute significantly to the pathogenesis of SLE.

Background: Systemic Lupus Erythematosus (SLE) is a chronic inflammatory autoimmune disease involving multiple organs. It is currently accepted that several genetic, environmental, and hormonal factors contributing to its development. Innate immunity may have a great influence in autoimmunity through Toll-like receptors (TLR). TLR-7 recognizing single-strand RNA has been involved in SLE. Its activation induces intracellular signal with attraction of MyD88 and NF-kB, leading to IFN-α synthesis which correlate with disease activity. Objective: To assess the expression of TLR-7, MyD88 and NF-kB in mononuclear cells of Mayan women with SLE. Methods: One hundred patients with SLE and one hundred healthy controls, all them Mayan women, were included. TLR-7 was analyzed on B and T lymphocytes, and MyD88 and NF-kB only in B lymphocytes. Serum INF-α level was evaluated by ELISA. Results: Significant expression (p < 0.0001) of TLR-7 in B and T lymphocytes and serum IFN-α increased (p = 0.034) was observed in patients. MyD88 and NF-kB were also increased in B lymphocytes of patients. TLR-7 and NF-kB expression correlated, but no correlation with INF-α and disease activity was detected. Conclusion: Data support the role of TLR-7 and signal proteins in the pathogenesis of SLE in the Mayan population of Yucatán.

Functional polymorphisms in pre-miR146a and pre- miR499 are associated with systemic lupus erythematosus but not with rheumatoid arthritis or Graves disease in Mexican patients Functional polymorphisms in pre-miR146a and pre-miR499 are associated with systemic lupus erythematosus but not rheumatoid arthritis or Graves’ disease in Mexican patients

Objective: Signal transducers and activators of transcription (STATs) are crucial mediators of cytokine signalling. Constitutive activation of STATs, especially STAT3, has been reported in several diseases. Primary Sjögren's syndrome (pSS) is associated with overproduction of cytokines such as interleukin‐10 (IL‐10), although the mechanism by which this occurs is unknown. As STAT3 is a potent inducer of IL‐10, this study focused on determining the pattern of STAT3 activation in peripheral lymphocytes from patients with pSS. Methods: Twelve pSS patients and 12 healthy age‐matched control subjects were studied. Peripheral blood mononuclear cells (PBMCs) were isolated by gradient centrifugation. Phosphorylated STAT3 (pSTAT3) and also STAT3 expression were determined by flow cytometry in gated CD3⁺ and CD19⁺ lymphocytes. Similarly, pJak1 and pTyk2 were also determined in gated CD3⁺ lymphocytes. Results: Although the protein expression of STAT3 was similar among controls and pSS patients, we found that STAT3 was constitutively activated in CD3⁺ lymphocytes from pSS patients. Neither Jak1 nor Tyk2 (the upstream activators of STAT3) was activated in pSS CD3⁺ lymphocytes, suggesting that the constitutive activation of STAT3 observed in pSS patients might not depend on cytokine stimulation but instead might be the result of an abnormal inactivation of pSTAT3. Conclusions: These data provide evidence of abnormal STAT3 signalling in T cells from pSS patients.