Аннотация
В обзоре рассматриваются актуальные аспекты исследования аутоантител при аутоиммунных заболеваниях печени (АИЗП). Аутоиммунный гепатит (АИГ) характеризуется обнаружением в сыворотках пациентов антинуклеарных антител (АNА), антител к гладкой мускулатуре (ASMA), микросомам печени и почек (LKM-1), цитоплазматическому антигену печени (LC-1), растворимому антигену печени/печеночно-панкреатическому антигену (SLA/LP), атипичных перинуклеарных антинейтрофильных цитоплазматических антител (pANCA), антител к асиалогликопротеиновому рецептору (ASGPR). Маркерами первичного билиарного холангита (ПБХ) являются антимитохондриальные антитела (АМА-М2), антиген-специфические ANA к sp100, gp210 и центромерам, антитела к антигенам Kelh-like 12 и Hexokinase-1. При первичном склерозирующем холангите (ПСХ) среди множества циркулирующих аутоантител наиболее часто идентифицируют атипичные pANCA. Представлен современный алгоритм исследования аутоантител при АИЗП. Стандартными диагностическими маркерами АИЗП служат ANA, ASMA, антитела к LKM-1 и AMA-M2. Комплексный анализ профилей стандартных и дополнительных субтипов аутоантител позволяет повысить чувствительность диагностики АИЗП и уменьшить количество «серонегативных» вариантов данных патологических состояний. Наибольшее прогностическое значение при АИГ и ПБХ имеют антитела к F-актину, LC-1, SLA/LP, ASGPR, sp100, gp210, центромерам, Kelh-like 12 и Hexokinase-1, обнаружение которых ассоциируется с высокой воспалительной активностью, тяжелым рецидивирующим течением заболевания, прогрессированием гистологического повреждения печени, циррозом, печеночной недостаточностью и необходимостью трансплантации печени. У больных ПСХ наличие атипичных рANCA и IgA-антител к GP2 в сыворотке крови является фактором риска обширного поражения желчевыводящих путей и развития холангиокарциномы. Перспективы иммунодиагностики АИЗП связаны с необходимостью стандартизации методов исследования аутоантител, поиском и клинической валидацией новых разновидностей данных биомаркеров на основе современных лабораторных технологий.
Annotation
The review discusses topical aspects of the study of autoantibodies in autoimmune liver diseases (AILD). Autoimmune hepatitis (AIH) is characterized by the detection in patient sera of antinuclear antibodies (ANA), antibodies to smooth muscle (ASMA), liver and kidney microsomes (LKM-1), liver cytoplasmic antigen (LC-1), soluble liver antigen/hepatopancreatic antigen (SLA/LP), atypical perinuclear antineutrophil cytoplasmic antibodies (pANCA), antibodies to asialoglycoprotein receptor (ASGPR). Primary biliary cholangitis (PBC) markers are antimitochondrial antibodies (AMA-M2), antigen-specific ANA to sp100, gp210 and centromeres, antibodies to Kelh-like 12 and Hexokinase-1 antigens. In primary sclerosing cholangitis (PSC), among the many circulating autoantibodies, atypical pANCAs are most frequently identified. A modern algorithm for the study of antibodies in AILD is presented. The standard diagnostic markers of AILD are ANA, ASMA, antibodies to LKM-1 and AMA-M2. Complex analysis of the profiles of standard and additional subtypes of autoantibodies makes it possible to increase the sensitivity of the diagnosis of AILD and reduce the number of «seronegative» variants of these pathological conditions. Antibodies to F-actin, LC-1, SLA/LP, ASGPR, sp100, gp210, centromeres, Kelh-like 12 and Hexokinase-1 have the greatest prognostic value in AIH and PBC, the detection of which is associated with high inflammatory activity, severe relapsing course diseases, progression of histological liver damage, cirrhosis, liver failure, the need for liver transplantation. In PSC patients, the presence of atypical pANCA and IgA antibodies to GP2 in the serum is a risk factor for extensive damage to the biliary tract and the development of cholangiocarcinoma. Prospects for the immunodiagnosis of AILD are associated with the need to standardize the methods for studying autoantibodies, the search and clinical validation of new varieties of these biomarkers based on modern laboratory technologies.
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