AUTOIMMUNE ASPECTS OF PREMATURE OVARIAN FAILURE

Background. The prevalence of premature ovarian failure (POF) of 1 % has important psychosocial consequences and impact on general health. Besides known etiology (genetic, chromosomal, infections, iatrogenic) autoimmunity can be the pathologic mechanism for POF. Material and methods. Eleven women with POF, with excluded other reasons for the disease except autoimmunity were included in this study. The control group consisted of 13 healthy normo-ovulatory women. In both groups targeted family and personal history was taken and determinations of: FSH, LH, TSH, prolactin, antimüllerian hormone (AMH), inhibin B, thyroid antibodies TG and TPO. At the cellular level periferal blood T-lymphocytes were analyzed by flow cytometry, on humoral level ovarian antibodies were detected with indirect immunofluorescence on human ovary sections. Quick ACTH test was performed in study group only. Results. In 9 patients POF was associated with another autoimmune disease. Six patients of the study group (55 %) presented very elevated thyroid autoantibodies TG and TPO, in the control group the levels of both autoantibodies were within normal range. Hormonal analyses in the study group exhibited the values of hypergonadotropic hypogonadism and consequently low levels of inhibin B and AMH. Lymphocyte subset in study group namely CD4+, CD19+ and CD8+ was significantly higher, while natural killer cells and regulatory T cells were significantly lower then in the control. group. In 4 patients (36 %) antiovarian autoantibodies were detected. Results of the quick ACTH test in the study group were normal. Conslusions. POF is frequently associated with autoimmune disorders. The presence of antithyroid and antiovarian antibodies together with abnormalities of the cellular immunity can potentionally represent an autoimmune mechanism of POF. The question of immunomodulatory therapy in selected patients with POF is open

Goodpasture's syndrome with concomitant immune complex mixed membranous and proliferative glomerulonephritis

Classical Goodpasture's (GP) syndrome is a monophasic illness characterized by pulmonary hemorrhage and rapidly progressive glomerulonephritis with linear IgG deposition along the glomerular and distal tubular basement membrane and destructive necrotizing diffuse extracapillary crescentic glomerulonephritis. The majority of patients have circulating anti-glomerular basement membrane (GBM) antibodies, detectable with standard anti-GBM ELISA. Concurrence of GP syndrome with proliferative glomerulonephritis has only rarely been described. In this report, for the first time we describe in a 21-year-old woman GP syndrome with 50% crescentic sclerosing glomerulonephritis with linear immunofluorescence characteristic of anti-GBM pathogenesis, combined with mixed membranous and membranoproliferative glomerulonephritis with granular immunofluorescence and subepithelial, mesangial and subendothelial deposits characterizing immune complex pathogenesis. The clinical picture was also unusual for GP syndrome, manifesting a recurrent but non-progressive course, nephrotic syndrome, normal renal function and low values of anti-GBM antibodies, identified only by novel more sensitive techniques

Performance evaluation of a novel chemiluminescence assay for detection of anti-GBM antibodies: an international multicenter study

Background. Autoantibodies to the non-collagen region (NC1) of the alpha-3 subunit of collagen IV represent a serological hallmark in the diagnosis of Goodpasture's syndrome (GPS). The objective of our study was to carefully analyze the performance characteristics of a novel anti-glomerular basement membrane (GBM) chemiluminescence immunoassay (CIA). Methods. Sera from patients with GPS (n = 90) were collected from four clinical centers. Samples from different disease groups (n = 397) and healthy individuals (n = 400) were used as controls. All samples were tested for anti-GBM antibodies by a rapid, random access CIA (QUANTA Flash (TM) GBM). Most of the samples were also tested using other methods including different commercial anti-GBM IgG assays and research assays for anti-GBM IgA and IgM. Results. The sensitivity and specificity of the novel CIA was 95.6% [95% confidence interval (CI) 89.0-98.8%] and 99.6% (95% CI 98.9-99.9%), respectively. Receiver operating characteristic analysis showed good discrimination between GPS patients and controls. The area under the curve was 0.98 (CI 0.96-1.0). The three anti-GBM antibody-positive samples from the control group were from two healthy individuals and one human immunodeficiency virus (HIV)-infected patient. All three individuals had low levels of anti-GBM antibodies [20, 24 and 25 chemiluminescent unit (CU), cutoff 20 CU]. When the results of the new CIA were compared to other methods, good agreement was observed: 95.8% (kappa = 0.92) versus EliA (TM) GBM, 97.4% (kappa = 0.95) versus both BINDAZYME (TM) Anti-GBM and QUANTA Lite (R) GBM. Anti-GBM IgA was detectable in low concentrations in patients with GPS and was associated with anti-GBM IgG but was less useful in discriminating GPS patients and controls. No discrimination was found for anti-GBM IgM. Conclusion. The novel QUANTA Flash (TM) GBM CIA demonstrated good sensitivity and specificity and had good agreement with other methods. Our data confirm that similar to 5% of patients with GPS do not have detectable levels of anti-GBM antibodies.TransplantationUrology & NephrologySCI(E)4ARTICLE1243-U2952

ROC curve with AUC for urine IgG to albumin ratio at the time of diagnosis.

<p>ROC curve with AUC for urine IgG to albumin ratio at the time of diagnosis.</p

Mean urine protein to creatinine ratio in responders (R) and non-responders (NR) in time.

<p>Mean urine protein to creatinine ratio in responders (R) and non-responders (NR) in time.</p

Mean of NAG to creatinine ratio in responders (R) and non-responders (NR) in time.

<p>Mean of NAG to creatinine ratio in responders (R) and non-responders (NR) in time.</p