vtioВестник трансплантологии и искусственных органовRussian Journal of Transplantology and Artificial Organs1995-1191Academician V.I.Shumakov National Medical Research Center of Transplantology and Artificial Organs", Ministry of Health of the Russian Federation10.15825/1995-1191-2016-3-39-49vtio-669Research ArticleКлиническая трансплантологияClinical TransplantologyАНАЛИЗ МЕТОДОВ СКРИНИНГОВОГО ОПРЕДЕЛЕНИЯ АНТИТЕЛ К HLA В ДИАГНОСТИКЕ АНТИТЕЛО-ОПОСРЕДОВАННОГО ОТТОРЖЕНИЯ ТРАНСПЛАНТАТА ПОЧКИCOMPARISON OF DIFFERENT METHODS OF ANTI-HLA ANTIBODIES DETECTION IN DIAGNOSIS OF ANTIBODY-MEDIATED RENAL ALLOGRAFT REJECTIONИвановаЕ. С.IvanovaE. S.

123182, г. Москва, ул. Пехотная, д. 3. Тел. (499) 196-17-94

3, Pekhotnaya St., Moscow, 123182, Russian Federation Tel. (499) 196-17-94

katerineiv@mail.ruСтоляревичЕ. С.StolyarevichE. S.

Кафедра нефрологии

Chair of Nephrology

ГичкунО. Е.GichkunO. E.БогдановаН. Б.BogdanovaN. B.БарановаФ. С.BaranovaF. S.АртюхинаЛ. Ю.ArtyukhinaL. Yu.ТомилинаН. А.TomilinaN. A.

Кафедра нефрологии

Chair of Nephrology

ФГБУ «Федеральный научный центр трансплантологии и искусственных органов имени академика В.И. Шумакова» Минздрава России, Москва; ГБУЗ «Городская клиническая больница № 52 Департамента здравоохранения г. Москвы», Московский городской нефрологический центр, МоскваРоссияV.I. Shumakov Federal Research Center of Transplantology and Artifi cial Organs of the Ministry of Healthcare of the Russian Federation, Moscow, Moscow; Moscow City Nephrology Center, Moscow City Hospital N 52, MoscowRussian FederationФГБУ «Федеральный научный центр трансплантологии и искусственных органов имени академика В.И. Шумакова» Минздрава России, Москва; ФПДО ФГБОУ ВО «Московский государственный медико-стоматологический университет им. А.И. Евдокимова», МоскваРоссияV.I. Shumakov Federal Research Center of Transplantology and Artifi cial Organs of the Ministry of Healthcare of the Russian Federation, Moscow, Moscow; A.I. Evdokimov Moscow State University of Medicine and Dentistry, MoscowRussian FederationФГБУ «Федеральный научный центр трансплантологии и искусственных органов имени академика В.И. Шумакова» Минздрава России, МоскваРоссияV.I. Shumakov Federal Research Center of Transplantology and Artifi cial Organs of the Ministry of Healthcare of the Russian Federation, Moscow, MoscowRussian FederationГБУЗ «Городская клиническая больница № 52 Департамента здравоохранения г. Москвы», Московский городской нефрологический центр, МоскваРоссияMoscow City Nephrology Center, Moscow City Hospital N 52, MoscowRussian Federation2016181120161833949Copyright © Иванова Е.С., Столяревич Е.С., Гичкун О.Е., Богданова Н.Б., Баранова Ф.С., Артюхина Л.Ю., Томилина Н.А., 20162016Иванова Е.С., Столяревич Е.С., Гичкун О.Е., Богданова Н.Б., Баранова Ф.С., Артюхина Л.Ю., Томилина Н.А.Ivanova E.S., Stolyarevich E.S., Gichkun O.E., Bogdanova N.B., Baranova F.S., Artyukhina L.Y., Tomilina N.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.transpl.ru/vtio/article/view/669

Цель исследования: оценка возможности скринингового выявления антител (АТ) к HLA I и II классов в сочетании с морфологическими и иммуногистохимическими методами для диагностики гуморального отторжения трансплантата и сравнение полученных данных в зависимости от применяемого метода определения АТ к HLA (ELISA и LUMINEX). Материалы и методы. Проанализированы данные 192 пациентов с дисфункцией почечного трансплантата, которым была выполнена биопсия трансплантата (c определением С4d) и исследованы АТ к HLA (у 109 пациентов методом ELISA, у 58 – методом LUMINEX, у 25 пациентов – и ELISA, и LUMINEX). На основании морфологического диагноза пациенты были разделены на 3 группы: 85 пациентов с хроническим отторжением трансплантата (ХОТ), 39 пациентов с острым гуморальным отторжением трансплантата (ОГО), 68 пациентов с иной патологией трансплантата (группа контроля). Результаты. АТ к HLA определялись у 84,7% пациентов с ХОТ, 84,6% пациентов с ОГО и у 33,8% (р < 0,001) в контрольной группе, причем резко доминировали АТ к HLA II класса. Меж- ду уровнем антител, выявляемых различными методами, определялась тесная корреляция (r² для АТ к HLA I класса составил 0,773, для АТ к HLA II класса – 0,379, р < 0,01). Однако при применении метода LUMINEX АТ к HLA выявлялись чаще во всех группах, что свидетельствует о большей его чувствительности. Особенно это значимо для диагностики C4d-негативного острого отторжения, частота которого составила 22,2% при LUMINEX vs. 4,8% при использовании метода ELISA. С другой стороны, АТ к HLA методом LUMINEX выявлялись у 55% пациентов контрольной группы, что требовало определения их донорспецифичности. Заключение. При наличии характерной морфологической картины и экспрессии С4d-фрагмента комплемента скрининговое определение АТ к HLA (методами ELISA, LUMINEX) является достаточным для диагностики гуморального отторжения. Однако в некоторых случаях необходимо применение более специфичных методов диагностики. 

Aim: to analyze the relationship between circulating anti-HLA antibodies (class-I and class-II), renal pathology and C4d deposition in cases of late acute and chronic antibody-mediated renal allograft rejection according to the method of antibodies detection (ELISA and LUMINEX). Materials and methods. Th e study included 192 patients with indicative graft biopsies (with C4d-staining) and screening detection of anti-HLA antibodies (109 patients by ELISA, 58 patients by LUMINEX, 25 patients – both methods). Patients were divided into 3 groups based on pathology fi ndings: 85 patients with chronic graft rejection, 39 patients with acute antibodymediated rejection (AMR), 68 patients of control group had no signs of AMR. Results. Anti-HLA antibodies (predominantly class-II anti-HLA) were identifi ed in 84.7% of patients with chronic graft rejection, in 84.6% of patients with acute AMR and 33.8% of control group (р < 0.001). Close correlation between the levels of antiHLA antibodies detected by different methods was revealed for both classes of antibodies (r² class-I anti-HLA = 0.773, r² class-II anti-HLA = 0.379, р < 0.01). LUMINEX proved to be more sensitive in anti-HLA antibodies detection in all groups. It was especially signifi cant for the diagnosis of C4d-negative acute AMR whose frequencies were 22.2% and 4.8% in detection by LUMINEX and ELISA, respectively (р < 0.01). On the other hand, anti-HLA antibodies being detected by LUMINEX in 55% of patients of the control group more often required determination of donor specifi city. Conclusion. Screening of anti-HLA antibodies (by ELISA and LUMINEX) along with specifi c renal pathology and C4d deposition is suffi cient for the diagnosis of acute and chronic AMR in most cases. Being more sensitive LUMINEX method is preferable for the revealing of C4d-negative AMR, but it requires specifi c DSA detection in many cases. 

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