Prevalence of anti-Toxoplasma antibodies in patients with autoimmune diseases.

The identification of etiological factors in the induction of autoimmunity has remained elusive despite an enormous effort at dissection of the molecular structure of the target antigens and effector mechanisms. One characteristic feature of autoantigens is their repetitive structure as well as their conservation and evolution. Toxoplasma (T.) gondii is a primitive protozoan. We hypothesized that patients with autoimmune disease would have broad reactions against Toxoplasma antigens based on autoantigen conservation. To address this issue, we assessed serologic evidence of reactivity to Toxoplasma gondii along with a large profile of autoantibodies in patients with various autoimmune diseases (AID). We included sera of 1514 patients with 11 different AID collected from referral centers in Europe and Latin America as well as from 437 geographically matched controls, for the prevalence of anti Toxoplasma antibodies (ATxA) IgG and IgM and serum autoantibodies utilizing the BioPlex 2200 system (Bio- Rad Laboratories, USA). Serum ATxA IgG were positive in 42% of patients with AID versus 29% of controls (p < 0.0001). Among Europeans, ATxA IgG were associated with anti-phospholipid syndrome (APS; p < 0.0001), cryoglobulinemia (p < 0.0001), ANCA-associated vasculitides (p < 0.01), autoimmune thyroid diseases (p < 0.0001), systemic sclerosis (SSc; p < 0.0001) and rheumatoid arthritis (RA; p < 0.0001). Of note, Latin American RA sera exhibited similar frequency of ATxA IgG as controls. ATxA IgM were more prevalent in European patients with APS (p < 0.01), SSc (p < 0.05) and inflammatory bowel disease (IBD, p < 0.05) than in controls. Further, in AID patients the presence of ATxA correlated with autoantibodies characteristic of APS (anti- cardiolipin, B2GPI, complex of cardiolipin- B2GPI, prothrombin, phosphatydilethanolamine), and of SSc (anti-centromere, Scl-70). Our findings suggest that T. gondii may contribute to the pathogenesis of AID. This interaction may depend on or explain observed geoepidemiological variance in AID.

Autoimmune bullous diseases the spectrum of infectious agent antibodies and review of the literature.

Pemphigus and bullous pemphigoid are two autoimmune diseases that have a similar pathogenesis. Both have a genetic predisposition which promotes the production of auto-antibodies targeted against different components of the epidermal desmosome and hemidesmosome. Environmental factors play an important role in the pathogenesis of this autoimmune disease. Among these, the role of infectious agents was debated as a causative factor. We sought to determine a possible connection between various infectious agents and autoimmune bullous disease (ABD). A cohort of 148 serum samples of patients with pemphigus, bullous pemphigoid and controls was screened for evidence of a prior infection with HBV, HCV, EBV, CMV, Helicobacter pylori, Toxoplasma gondii and Treponema pallidum, utilizing the Bio-Rad BioPlex 2200 system as well as ELISA assays to complete the panel. HBV, HCV, H. pylori, T. gondii and CMV were demonstrated to have significantly higher prevalence of antibodies in patients with pemphigus and bullous pemphigoid in comparison to controls. Among them, we found a novel association between H. pylori and ABD. Our study suggests a contributing role for HBV, HCV, H. pylori, T. gondii and CMV in inducing ABD in the genetically susceptible host.

A comprehensive evaluation of serum autoantibodies in primary biliary cirrhosis.

In primary biliary cirrhosis (PBC) serum markers other than anti-mitochondrial antibodies (AMA) are promising in terms of disease severity and comorbidities, as well represented by anti-nuclear antibodies (ANA). The aim of the present study was thus to evaluate the prevalence and clinical significance of a large profile of serum autoantibodies in PBC sera. We utilized 69 sera from European patients with PBC (including 20 AMA-negative) and 297 sera from geographically and sex-matched healthy controls. All sera were tested for the presence of ANA and autoantibodies associated with thrombophilia, vasculitis, and gastrointestinal disease. Autoantibodies other than AMA were detected in 53/69 (76%) PBC sera vs. 105/297 (35%) among controls. The prevalence of ANA (targeting dsDNA, Sm, chromatin, ribosomal-P, RNP, SmRNP, SSA, SSB, and centromere) and thrombophilia-associated autoantibodies (i.e. anti-beta2GPI, phosphatydilserine, prothrombin) was common among patients with PBC. When clinical features were compared, the presence of anti-prothrombin IgM was associated with a worse prognosis as represented by a higher Mayo score. We demonstrate an increased prevalence of ANA and thrombophilia-associated autoantibodies in PBC sera and an association between the latter autoantibodies and PBC stage. The role of thrombophilia-associated antibodies will warrant further studies, based in particular on the incidence of portal hypertension at early stages of PBC.

Anti-ribosomal-P antibodies in lupus patients and healthy controls: evaluation of three ELISA assays.

BACKGROUND: Anti-ribosomal-P antibodies have been associated with central nervous system manifestations of systemic lupus erythematosus. However, inconsistencies in their prevalence and clinical correlations have become an obstacle to their use as a diagnostic marker of the disease. This lack of consistency might stem from several factors, such as the lag period between clinical manifestations and the time blood was drawn; or the different methods used for antibodies detection. OBJECTIVES: To evaluate three different enzyme-linked immunosorbent assay tests for the detection of anti-Rib-P Abs in patients with SLE and in normal controls. METHODS: Sera from 50 SLE outpatients and 50 healthy subjects were tested with three ELISA kits: Kit-1, using synthetic peptide comprising the 22 C-terminal aminoacids; Kit-2, using native human ribosomal proteins (P0, P1, P2); and Kit-3, which is coated with affinity-purified human ribosomal proteins. ELISA studies were performed according to the manufacturers' instructions. RESULTS: The prevalence of anti-Rib-P Abs in SLE patients and controls was 30% vs. 0%, 17% vs. 21%, and 30% vs. 14% in kits 1-3 respectively. Anti-Rib-P Abs detected by Kit-1 correlated with the SLEDAI score (SLE Disease Activity Index). No correlation between prior CNS manifestations and anti-Rib-P Abs was observed. CONCLUSIONS: A significant difference was documented between the ELISA kits used for the detection of anti-Rib-P Abs. A correlation was found between these antibodies (evaluated by Kit-1) and concurrent SLEDAI scores, in contrast to the lack of correlation with previous CNS manifestations. This supports the notion of "active serology" that is evaluated at the same time manifestations are present, as well as the need for standardization of laboratory assays in the future which will enable a better assessment of anti-Rib-P Abs presence and clinical significance.

Infection and primary biliary cirrhosis.

Primary biliary cirrhosis is an autoimmune cholestatic liver disease characterized by humoral and cellular response directed at mitochondrial autoantigens, mainly the E2 component of the pyruvate dehydrogenase complex. The etiology of PBC, like most polygenic autoimmune diseases, belongs to the "complex" category, including genetic elements and environmental factors. Many environmental factors, such as xenobiotics, smoking, hormonal therapy, toxins, oxidative stress and recurrent urinary tract infections, are associated with PBC. Infectious agents can trigger autoimmunity via several mechanisms and are associated with various autoimmune diseases. A relationship between PBC and several infectious agents, and a possible role for Escherichia coli in the pathogenesis of PBC, have been suggested. The identification of a culprit agent that induces or exacerbates PBC might have diagnostic and therapeutic implications. This review evaluates the evidence for an infectious agent role in the pathogenesis of PBC.

The sense of smell in systemic lupus erythematosus.

OBJECTIVE: To assess the olfactory functions in systemic lupus erythematosus (SLE) patients compared with age- and sex-matched healthy controls, and to examine the association between the sense of smell and disease activity and central nervous system (CNS) involvement. METHODS: Olfactory functions in 50 SLE patients and 50 age- and sex-matched controls were evaluated using the Sniffin' Sticks test, the 3 stages of which are threshold, discrimination, and identification (TDI) of different odors. TDI scores were analyzed according to SLE disease activity and CNS involvement. RESULTS: In both the SLE and control groups, smell deficit correlated with male sex and older age. A decrease in the sense of smell was observed in SLE patients (46%) and controls (25%) (P