Androgen and prolactin (Prl) levels in systemic sclerosis (SSc) relationship to disease severiny
ABSTRACT Testosterone (T), sex hormone-binding globulin, (SHBG), dehydroepiandrosterone sulfate (DHEAS), and prolactin (Prl) serum levels were measured by electrochemiluminescense immunoassay (ECLIA) in 39 patients with systemic sclerosis (SSc) and compared with serum hormonal levels in control subjects matched for sex and reproductive status. A possible relationship with disease duration and disease severity was examined. Our data show an altered androgen and prolactin (Prl) status in SSc patients, in most cases related to disease duration and disease severity score. We can hypothesize that hormonal dysregulation is a consequence of the chronicity of the disease. The altered hormonal status could result in relative immunological hyperactivity contributing to enhance tissue damage and disease severity.
Article: Gender and autoimmunity[Show abstract] [Hide abstract]
ABSTRACT: The enhanced immunoreactivity in females is a double-edged sword that provides better protection against infections, but may lead to enhanced autoreactivity and thereby contribute to the induction of autoimmunity. Autoimmune diseases demonstrate a gender bias and represent the fifth leading cause of death by disease among females of reproductive age. Clinical and murine experimental studies indicate that the gender bias in autoimmunity may be influenced by sex hormones, predominantly displayed in the development and exacerbations of the prototypical autoimmune disease lupus. The associations between sex hormones and other autoimmune diseases are less clear. Our review on the impact of gender via sex hormones and sex related genes in the pathogenesis of several autoimmune diseases suggests that a better understanding of the underlying mechanisms behind the sexual dimorphism of the immune system may lead to the development of novel therapeutic approaches to autoimmunity.Autoimmunity Reviews 07/2007; 6(6):366-72. DOI:10.1016/j.autrev.2006.10.001 · 7.10 Impact Factor
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ABSTRACT: More than 50 different neurological pathologies have a confirmed or suspected autoimmune etiology affecting an estimated number of 75 million people worldwide. Autoantibodies are a useful diagnostic marker for most autoimmune diseases even though their pathological role is not evident, and several tests for their detection are commercially available. However, for autoimmune diseases involving the nervous system, lack of clear information on the identity of antineural antibody targets and the presence of many rare diseases have hampered the development of specific diagnostic assays. This review focuses on the actual knowledge on confirmed and suspected autoimmune diseases that target the CNS and the diagnostic relevance of corresponding antineural autoantibodies.Expert Review of Clinical Immunology 11/2007; 3(6):949-73. DOI:10.1586/1744666X.3.6.949 · 3.34 Impact Factor
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ABSTRACT: Autoimmune diseases predominantly affect women, suggesting that female sex hormones may play a role in the pathogenesis of such diseases. We have previously shown that persistent mild-to-moderate elevations in serum prolactin levels induce a break in self tolerance in mice with a BALB/c genetic background. The aim of this study was to evaluate the effects of hyperprolactinemia on the mechanisms of B cell tolerance induction. Effects of prolactin on splenic B cell subsets were studied in female BALB/c mice. B cell receptor (BCR)-mediated apoptosis and proliferation of transitional B cells were analyzed by flow cytometry. Expression of apoptotic genes was examined by microarrays and real-time polymerase chain reaction analysis. B cells coexpressing kappa/lambda light chains were assessed by flow cytometry and immunohistochemistry. Activation status of transitional type 3 (T3) B cells was evaluated by BCR-induced calcium influx studies. BCR-mediated apoptosis of the T1 B cell subset, a major checkpoint for negative selection of autoreactive specificities, was decreased in prolactin-treated mice. Microarray studies indicated that this event may be mediated by the prolactin-induced up-regulation of the antiapoptotic gene interferon-gamma receptor type II and down-regulation of the proapoptotic gene Trp63. Prolactin treatment also altered the amount of receptor editing, as indicated by the increased number of transitional B cells coexpressing kappa/lambda light chains. Additionally, hyperprolactinemia modified the level of B cell anergy by increasing the degree of BCR-induced calcium influx in the T3 B cells. Persistently elevated serum prolactin levels interfere with B cell tolerance induction by impairing BCR-mediated clonal deletion, deregulating receptor editing, and decreasing the threshold for activation of anergic B cells, thereby promoting autoreactivity.Arthritis & Rheumatology 06/2009; 60(6):1743-52. DOI:10.1002/art.24500 · 7.87 Impact Factor