C3 glomerulopathy: a long way from the light microscopy findings to the targeted therapy

C3 glomerulopathy is an ultra-rare disease, driven by alternative complement pathway dysregulation, which results in C3 deposition in glomeruli. History of studying the conditions, currently merged under the umbrella of C3 glomerulopathy (С3 GP), counts more than 60 years of capturing substantial changes in the understanding of both pathology and pathogenesis of these diseases. The main pathogenetic factors are either (more commonly) acquired - antibodies against alternative pathway convertases, or (less commonly) genetic - mutations of genes, encoding alternative pathway regulators. The disease phenotype is triggered by autoimmune conditions, infections, or monoclonal gammopathy. The clinical course of C3 GP varies from mild proteinuria and hematuria to rapidly progressive glomerulonephritis syndrome. The decrease of serum C3 levels serving as an important biomarker of the alternative pathway activation is not always detectable; however, normal C3 levels do not rule out C3 GP diagnosis. The key diagnostics tool is immunostaining, demonstrating isolated or dominant C3 expression, while light microscopy commonly, but not exclusively, shows a membranoproliferative pattern of injury. Clinical course and response to the immunosuppressive treatment depend on such factors as genetic predisposition, age of the disease onset, and presence of specific autoantibodies or monoclonal immunoglobulins. Genetic investigations play an important auxiliary role in the diagnostics of genetic forms of C3 GP, genetic abnormalities are important predictors of the response to immunosuppressive treatmentи and they are key determinates for the evaluation of recipients and potential relative donors for kidney transplantation. Response to the currently recommended treatment of the moderate-to-severe C3 GP with glucocorticosteroids and mycophenolates is not universal, however, emerging new molecules against complement cascade factors, as well as clone-oriented treatment, open perspectives for the targeted individualized therapy, which efficacy remains to be further studied and evaluated.

комплемент, биопсия почки, болезнь плотных депозитов, С3 гломерулонефрит, С3-нефритический фактор, генетические исследования, complement, kidney biopsy, dense deposit disease, С3 glomerulonephritis, C3-nephritc factor, genetic testing

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