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OBJECTIVE: Rheumatoid Arthritis (RA) is an autoimmune inflammatory disease that leads to local and systemic arthritis and bone loss. Exploring genetic markers of candidate genes in osteoporosis and inflammatory cytokine genes could be a useful tool for the early identification of bone loss and fracture risk in RA patients. The target of this study is the evaluation and correlation between of Single Nucleotide Polymorphisms (SNPs) of Vitamin D Receptor (VDR) and possible effects on bone loss in RA. PATIENTS AND METHODS: 40 Caucasian patients with RA (26 of them with a severe bone loss) and 40 healthy donors as control samples were genotyped for the VDR SNPs (called BsmI, ApaI, TaqI and FokI). The detection method is based on Restriction Fragment Length Polymorphism (RFLP). RESULTS: Genotyping profile shown no difference between RA patients and controls. Only VDR-TaqI genotype (TT vs. tt) seem to influence the bone density in females, but not in males. The mean differences of Bone Mass Density (BMD) at the lumbar spine in RA women with the tt allele were 4.7% compared to 0.1% in women with the TT allele (p < 0.05). CONCLUSIONS: The results of these studies support an association between specific VDR alleles and bone loss in RA. The TaqI t and BsmI B alleles were associated with an accelerated bone loss in RA, but not with a focal bone loss. These effects of VDR genotypes and vitamin D supplementation are not unexpected, given that the central pathological feature in RA is bone and joint destruction. The VDR SNPs genotyping should be a useful tool to screen early women RA patients with the bone loss.

Hashimoto's thyroiditis (HT) is an autoimmune disorder characterized by the presence of specific antibodies and by a lymphocytic infiltration of the thyroid secreting inflammatory cytokines. Macrophages, lymphocytes and cytokines play a pivotal role in both development and progression of Th1-mediated autoimmune diseases, and a direct role in the destruction of thyroid follicles and follicular cell function in autoimmune thyroiditis. Integrins are integral membrane receptors involved in cell-extra-cellular matrix (ECM) interaction with both structural and signaling functions. The integrin-ECM interaction is necessary for the correct function and survival of thyroid follicular cells. The purpose of this study was to determine the effect of cytokine stimulation on integrin expression and signaling in the thyroid cell. Primary cultures from normal thyroids were treated with interferon-γ (IFN-γ), INF-α, tumor necrosis factor-α, interlukin 1a or these cytokines all together. Integrin expression, cell adhesion to fibronectin (FN) and FN-stimulated ERK phosphorylation were determined after cytokine treatment. IFN-γ and IFN-α were the most effective, reducing the expression of the integrin αvβ3 and slightly increasing the α3β1. Cell treatment with IFN-γ strongly impaired cell adhesion to FN. At the same time, the treatment with IFN-γ dramatically inhibited the stimulation of ERK phosphorylation induced by cell adhesion to FN. In conclusion, IFN-γ inhibits the expression of the integrin αvβ3, reducing the cell adhesion to FN and the following intracellular signaling in thyroid cells in culture. These results suggest that integrins may be a target of the infiltrating lymphocytes and have a role in the pathogenesis of autoimmune thyroiditis.

recombinant allergens,natural allergens extracts, pollen hypersensitivity,component-resolved diagnosis

Background. Systemic sclerosis (SSc) is an autoimmune disease characterized by excessive fibrosis in derma fibroblasts. There are two major subsets of SSc, the diffuse cutaneous systemic sclerosis (dSSc) and the limited cutaneous systemic sclerosis (lSSc). Fibroblasts play a key role in SSc. The expression and function of the urokinase (uPA)-mediated plasminogen activation (PA) system, a well characterized system of serine-proteases involved in several pathologic processes, has been investigated in SSc fibroblasts. Methods. The expression of the components of the PA system, including uPA, its receptor (uPAR) and its type-1 and type-2 inhibitors (PAI-1 and PAI-2) was examined by Western blot in fibroblasts from patients affected by limited and diffuse forms of SSc. SSc fibroblasts adhesion to vitronectin (VN) was examined by cell adhesion assays. Results. uPA and PAI-1 secretion increased only in fibroblasts from lSSc lesions, as compared to normal fibroblasts. PAI-2 levels were decreased in fibroblasts from both SSc forms. Interestingly, fibroblasts from areas not adjacent to the lesions (not-affected) of the diffuse form showed reduced levels of PAI-1 and increased uPAR expression. Adhesion experiments showed reduced adherence to VN of fibroblasts from lSSc and dSSc lesions in from not affected areas, as compared to normal controls. Conclusions. These results suggest a role for uPA and PAI-1 in the lSSc form, likely related to the activation of cytokines and metalloproteases with the accumulation of extra-cellular matrix components, whereas a role for uPAR can be hypothesized in the evolvement of the diffuse form, based on its up-regulation in the not-affected areas.

Hepatitis C Virus (HCV) infection can induce immunological disorders with different clinical expressions such as arthritis, Sjogren Syndrome and various forms of vasculitis. Retrospectively, the prevalence of anti-Cyclic Citrullinated peptide antibodies (anti-CCP) in a group of patients affected by HCV-related arthritis with positivity for Rheumatoid Factor (RF) and the eventual correlations with RF and/or Anti-Nuclear Antibodies (ANA) and articular involvement were studied. Thirty patients with arthritis were selected from a population of 380 subjects affected by HCV infection. Each patient was evaluated by clinical examination (23 denoted poliarticular and 7 mono-oligoarticular involvement), by X-graphic aspects of joint involvement (8 patients presented joint erosions), by ANA, RF and anti-CCP positivity. Ten of the HCV-related arthritis patients (33.3 percent) presented positivity for anti-CCP, without significant correlation between such parameter and ANA, RF and articular involvement. Anti-CCP resulted positive in 4 out of the 8 patients with joint erosions, and only in 6 out of the 22 patients without joint erosions. Such frequencies analyzed by chi square resulted with no significant differences. Our patients presented an interesting prevalence of the positivity for anti-CCP. These data are cause to consider the specificity recently attributed to this parameter in the diagnosis of rheumatoid arthritis.

Soluble gp130 (sgp130) is a soluble circulating receptor of IL-6 with "antagonistic" biologic activity. It is generated independently by either shedding of the extracellular domain of membrane gp130 or alternative mRNA splicing. This study was addressed to clarify the mechanisms underlying sgp130 synthesis and release in patients who undergo regular dialysis treatment (RDT) using dialytic membranes with different biocompatibility. Two groups of RDT patients were enrolled: 11 patients who were treated with cellulosic membranes (C) and 10 patients who were treated with synthetic membranes (S). Ten healthy subjects constituted the control group. Serum samples and peripheral blood mononuclear cells (PBMC) were harvested in all groups (before dialysis in RDT patients). PBMC were cultured for 24 h in the absence or presence of LPS. The serum levels of sgp130 were significantly higher in C group than in control and S patients (C, 603.1 +/- 89.9; control, 396 +/- 49.5; S, 423.4 +/- 27.7 ng/ml; P < 0.01). PBMC from C patients, in the absence of any mitogenic stimulation, released a significantly greater amount of sgp130 as compared with S and control groups (C, 532.6 +/- 161.2; S, 332.4 +/- 148.6; control, 341.4 +/- 125.4 pg/ml; P < 0.01). The sgp130 release was positively correlated with the release of both IL-6 (r = 0.336, P < 0.05) and sIL-6R receptor (r = 0.324, P < 0.05). A significantly higher gp130 gene expression was also observed in unstimulated PBMC from C patients when compared with control and S groups. It is interesting that the expression of the 85-bp exon characteristic of the alternative splicing mRNA for sgp130 was low in all groups. Finally, confocal microscopy analysis showed an increased expression of gp130 on cell surface in unstimulated PBMC from C patients as compared with control and S groups. Our results demonstrate that in patients on RDT with C membranes, the synthesis and release of sgp130 "antagonistic" receptor is significantly increased. This release is seemingly due to a shedding of membrane-bound gp130 receptor. The increased sgp130 release may partially counteract the inflammatory effects caused by IL-6.

In remodeling ventricles, the progression of heart failure is associated with structural changes involving the extra-cellular matrix (ECM) and the cytoskeletal filament of myocardiocytes, associated with fibrosis, cellular damage and death, which lead to alterations in heart geometry, size and mechanical properties. Recently several observations have demonstrated the role of some cytokines and haemopoietic growth factors in the damage and regeneration mechanisms of cardiac tissue during acute myocardial infarction. After heart damage, the development of scarred tissue has been considered as the only reaction, since myocytes are thought to be terminally differentiated cells and thus unable to proliferate. On the contrary, recent studies in animal models and adult human hearts have shown that myocytes can proliferate before reaching their final size and that their proliferation may be stimulated and modulated by several factors. Against this background, we have investigated the expression of the receptor for GM-CSF, an haemopoietic growth factor, in healthy and end-stage human cardiac tissues, to clarify the possible role of GM-CSF and its receptor in the regenerative process of cardiac tissue in chronic cardiomyopathy. We have studied GM-CSFR expression on human cardiac tissue from explanted hearts of chronic patients with heart failure (ischemic and dilatative cardiomyopathy) and on cardiac biopsies from normal human hearts, by immunohistochemistry, cellular and molecular biology assays. Our results demonstrated the presence of GM-CSFRb in cardiac tissue; in particular GM-CSFRb positive cells were a constant finding in pathological cardiac tissues and significantly increased as compared to normal control tissues. At the moment we can only hypothesize that GM-CSF, like other growth factors, plays a role in apoptotic and/or ECM deposition processes as well as in the cytoskeleton modification in myocardium.