rspНаучно-практическая ревматологияRheumatology Science and Practice1995-44841995-4492IMA-PRESS, LLC10.14412/1995-4484-2016-86-99rsp-2173Research ArticleОБЗОРREVIEWАутоантитела при системной склеродермии: спектр, клинические ассоциации и прогностическое значениеAUTOANTIBODIES IN SYSTEMIC SCLEROSIS: SPECTRUM, CLINICAL ASSOCIATIONS, AND PROGNOSTIC VALUEАнаньеваЛ. П.AnanyevaL. P.

Москва, 115522 Москва, Каширское шоссе, 34А

Moscow, 34A, Kashirskoe Shosse, Moscow 115522

lpana@yandex.ruАлександроваЕ. Н.AleksandrovaE. N.

Москва, 115522 Москва, Каширское шоссе, 34А

Moscow, 34A, Kashirskoe Shosse, Moscow 115522

ФГБНУ Научно-исследовательский институт ревматологии им. В.А. НасоновойРоссияV.A. Nasonova Research Institute of RheumatologyRussian Federation2016230320165418699Copyright © Ананьева Л.П., Александрова Е.Н., 20162016Ананьева Л.П., Александрова Е.Н.Ananyeva L.P., Aleksandrova E.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://rsp.mediar-press.net/rsp/article/view/2173

Цель обзора – клиническая оценка циркулирующих аутоантител при системной склеродермии (ССД). Подробно рассмотрены «болезнь-специфические», т. е. ассоциированные с заболеванием, антиядерные аутоантитела: к центромерам, к топоизомеразе 1; группа антинуклеолярных антител – к рибонуклеопротеазе III (АРНКП-III), Th/T0, Pm/Scl, а также аутоантитела к рибонуклеопротеинам UIRP и U3RNP. Частота выявления антиядерных аутоантител высока (90–95%), при этом каждое из аутоантител в отдельности обнаруживается у небольшого числа больных с определенными клинической картиной, характером течения, прогнозом и имеет четкие генетические ассоциации. Показана четкая ассоциация между типом аутоантител, характером органных осложнений и выживаемостью. Специфичные аутоантитела относятся к предикторам течения болезни и ее исхода. Насколько клинические различия между подгруппами отражают патогенетические различия иммунной дисрегуляции, остается неясным. Специфичные для ССД аутоантитела появляются на самом раннем этапе заболевания, до того как клиническая картина болезни станет развернутой. Подробно описаны их диагностическая значимость и место в новых классификационных критериях заболевания 2013 г. Обоснована важность внедрения в клиническую практику определения антицентромерных, антитопоизомеразных аутоантител и антител к РНК-протеиназе III. Определение антител к РНК-протеиназе III имеет большое значение в связи с важностью выделения особого подтипа ССД, потенциально имеющего плохой прогноз, в том числе в связи с повышенной частотой развития онкологических заболеваний. Представляется целесообразным при формулировке диагноза больного ССД указывать его позитивность по основным «склеродермическим» аутоантителам.

Последний раздел обзора посвящен неспецифическим аутоантителам, направленным на такие мишени, как эндотелиальные клетки и фибробласты, функциональные молекулы (различные клеточные рецепторы), белки экстрацеллюлярного матрикса, энзимы и др. Затронут ряд интересных гипотез и теорий, объясняющих инициирующую роль этой подгруппы аутоантител в возникновении и развитии ССД.

The purpose of the review is to clinically evaluate circulating autoantibodies in systemic sclerosis (SS). The diseasespecific, i.e. disease-associated, antinuclear autoantibodies: to centromeres, to topoisomerase 1; a group of antinuclear antibodies to ribonucleoprotease III, Th/T0, Pm/Scl, as well as autoantibodies to ribonucleoproteins U1 RNP and U3 RNP are considered in detail. The detection rate of the antinuclear autoantibodies is high (90–95%); at the same time, each of the autoantibodies is detectable separately in a small number of patients with certain clinical presentation, patterns of the course, and prognosis and has clear genetic associations. There is a clear association between the type of autoantibodies, the nature of organic complications, and survival rates. Specific autoantibodies belong to predictors for the course of the disease and its outcome. How much the clinical distinctions between the subgroups reflect pathogenetic differences in immune dysregulation remains unclear. SS-specific autoantibodies emerge in the earliest stage of the disease until the clinical picture of the disease becomes extensive. Their diagnostic value and place in the 2013 new classification criteria for the disease are described in detail. There is evidence that it is important to introduce the determination of anti-centromere, anti-topoisomerase autoantibodies and anti-RNA proteinase III antibodies into clinical practice. The detection of the latter is essential due to the importance of identifying a special subtype of SS, which has a potentially poor prognosis, among other factors, due to the increased incidence of cancers. When making the SS diagnosis, it is appropriate to indicate its positivity for main scleroderma autoantibodies.

The last section of the review deals with the non-specific autoantibodies directed against targets, such as endothelial cells and fibroblasts, functional molecules (different cell receptors), extracellular matrix proteins, enzymes, etc. A number of interesting hypotheses and theories, which explain the initiating role of this subgroup of autoantibodies in the occurrence and development of SS, are considered.

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The authors declare that there are no conflicts of interest present.