Infectious serologies and autoantibodies in hepatitis C and autoimmune disease-associated mixed cryoglobulinemia

Mixed cryoglobulinemia (MC) syndrome is an immune complex-mediated vasculitis characterized by the clinical triad of purpura, weakness, and arthralgias, the morbidity of which is mainly related to kidney and peripheral nervous system dysfunction as well as to the development of a secondary lymphoma (Ferri et al. Autoimmun Rev 7:114-120, 2007, Lidar et al. Ann N Y Acad Sci 1173:649-657, 2009, Trejo et al. Semin Arthritis Rheum 33:19-28, 2003). MC is associated with infectious and systemic disorders, principally autoimmune and lymphoproliferative diseases. Since the 1990s, a striking association (>90%) between MC and hepatitis C virus (HCV) infection has been established (Ferri and Bombardieri 2004; Pascual et al. J Infect Dis 162:569-570, 1990). However, information regarding the etiopathogenesis of HCV-negative MC is scant (Mascia et al. Dig Liver Dis 39:61-64, 2007). We hereby present our findings, as well as previously published data, regarding the presence of antibodies against infectious agents and autoantibodies in patients with MC in an attempt to establish novel associations which may shed light on the etiopathogenesis of this diseas

Vitamin D: an instrumental factor in the anti-phospholipid syndrome by inhibition of tissue factor expression

BACKGROUND AND AIMS: Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterised by thrombosis, obstetric complications and the presence of anti-phospholipid antibodies such as anti-\u3b22GPI-Abs. These antibodies may set off the coagulation cascade via several mechanisms, including the induction of tissue factor (TF) expression. Vitamin D has recently emerged as an immunomodulator that might exert an anti-thrombotic effect. Therefore, we studied serum vitamin D levels in a cohort of APS patients, as well as the effect of vitamin D in an in vitro model of APS-mediated thrombosis. METHODS: Serum vitamin D levels were measured in 179 European APS patients and 141 healthy controls using the LIAISON chemiluminescent immunoassay, and the levels were evaluated in conjunction with a wide spectrum of clinical manifestations. In an vitro model, anti-\u3b22GPI antibodies were purified from four patients with APS to evaluate the expression of TF in activated starved human umbilical vein endothelial cells. The effect of vitamin D (1,25-dihydroxyvitamin D, 10 nm) on anti-\u3b22GPI-Abs mediated TF expression was analysed by immunoblot. RESULTS: Vitamin D deficiency (serum level 6415 ng/ml) was documented in 49.5% of our APS patients versus 30% of controls (p<0.001) and was significantly correlated with thrombosis (58% vs 42%; p<0.05), neurological and ophthalmic manifestations, pulmonary hypertension, livedo reticularis and skin ulcerations. In vitro vitamin D inhibited the expression of TF induced by anti-\u3b22GPI-antibodies. CONCLUSIONS: Vitamin D deficiency is common among APS patients and is associated with clinically defined thrombotic events. Vitamin D inhibits anti-\u3b22GPI-mediated TF expression in vitro. Thus, vitamin D deficiency might be associated with decreased inhibition of TF expression and increased coagulation in APS. Evaluation of vitamin D status and vitamin D supplementation in APS patients should be considere

Infectious serologies and autoantibodies in Wegener's granulomatosis and other vasculitides: novel associations disclosed using the Rad BioPlex 2200

In this study we assess the presence of antibodies against infectious agents as well as for a variety of autoantibodies in an attempt to establish associations between various vasculitides and infections in order to shed light on the etiopathogenesis of these diseases and perhaps implicate a potential cure. Sera from patients with Wegener's granulomatosis (WG), polyarteritis nodosa, microscopic polyangiitis, Churg Strauss, and giant cell arteritis were compared to healthy control sera. Serum samples were assessed, using the Bio-Rad BioPlex 2200, for the presence of Toxoplama gondii, cytomegalovirus (CMV), Epstein-Barr virus (EBV), Treponema pallidum, and Saccharomyces cerevisiae. Hepatitis B virus (HBV), hepatitis C virus (HCV), and anti-Helicobacter pylori antibodies were assessed by ELISA. In addition, sera were tested for a panel of antibodies associated with thrombophilia as well as various autoantibodies. The prevalence of antibodies toward HCV and H. pylori was significantly higher among patients with WG. IgG antibodies toward T. gondii and IgM antibodies toward CMV were significantly more common among WG patients than among controls. WG patients exhibited more antibodies toward EBV viral capsid antigen IgG and EBV early antigen IgG compared to sera from healthy controls. In WG, positive associations were disclosed between CMV IgG antibodies and the presence of gastrointestinal manifestations and renal involvement, and there was a higher Birmingham vasculitis activity score in association with elevated titers of EBV viral capsid antigen IgG antibodies. Otorhinolaryngeal manifestations were more common in those with positive IgG antibodies for EBV early antigen. Our results unveil novel associations between WG and various infectious agents, including HCV, H. pylori, T. gondii, CMV, and EBV. In addition to putative roles in initiation and exacerbation of the vasculitic process, it seems that these infectious agents also modulate the clinical phenotype of the disease

Prevalence of hepatitis C serum antibody in autoimmune diseases

The association of systemic lupus erythematosus (SLE) and thyroid autoimmunity has been reported by several studies in a wide range of variability. However, from a review of the literature, discrepant results have been reported. The aim of the study was to evaluate the prevalence of clinical and subclinical thyroid disorders in patients with SLE vs sex- and age-matched controls. Thyroid hormones and the presence of antithyroid antibodies were tested and thyroid ultrasonography was performed in 213 patients with SLE vs 426 sex- and age-matched controls, from the same geographic area, with a well-defined status of iodine intake. The odds ratio for subclinical hypothyroidism for female patients with SLE with respect to controls was 4.5 (95% confidence interval [CI], 2.5-8.4); for antithyroid peroxidase antibody (AbTPO) positivity, it was 2.6 (95% CI, 1.7-4.1); and for thyroid autoimmunity, it was 2.9 (95% CI, 2.0-4.4). The mean values of thyroid-stimulating hormone and AbTPO were higher in female SLE patients than in controls (P < .01). A significantly (P < .01) higher prevalence of clinical hypothyroidism and Graves disease was observed in female SLE patients than in controls. No significant difference between SLE patients and controls was detected with regard to free triiodothyronine and thyroxine. In our series, 3% of SLE patients had "nonthyroidal illness syndrome" vs 0 control. Thyroid function and AbTPOs should be tested and ultrasonography should be performed as part of the clinical profile in SLE patients. Subjects at high risk (women, positive AbTPOs, hypoechoic, and small thyroid) should have thyroid function follow-up and appropriate treatment in due course