Analysis of complement biomarkers in systemic sclerosis indicates a distinct pattern in scleroderma renal crisis

Abstract

BackgroundThe complement system has been implicated in pathogenesis of systemic sclerosis (SSc). The goal of the present study was to evaluate improved complement biomarkers in SSc.MethodsThe presence of C4d, reflecting activation of the classical/lectin pathways, C3bBbP corresponding to activation of the alternative pathway, and soluble terminal complement complexes (all complement pathways), was measured in plasma samples by enzyme-linked immunosorbent assay and correlated to clinical parameters. The study included 81 patients with limited cutaneous SSc and 41 with diffuse cutaneous SSc, as well as 47 matched healthy controls and 81 patients with rheumatoid arthritis, 22 with psoriatic arthritis and 20 with ankylosing spondylitis. Skin and kidney biopsies of selected patients were stained to detect deposited C3b as a marker of local complement activation.ResultsBiomarkers of activation of all complement pathways were increased in SSc compared with healthy controls and were similar to those in other rheumatic diseases. When patients with SSc were divided into subgroups, a distinct pattern of complement markers was observed in individuals with scleroderma renal crisis (SRC). By functional assay, we confirmed a significant decrease in complement haemolytic activity in SRC vs. non-SRC patients, indicating complement consumption. Further, we detected glomerular deposits of C3b in some patients with SRC.ConclusionsThe data indicate that complement activation is an important feature of SRC.

Complement activation in atypical hemolytic uremic syndrome and scleroderma renal crisis: a critical analysis of pathophysiology

“… 38 Very recently, a Swedish study demonstrated that patients with SRC had lower levels of C3 and factor B secondary to over-activation of the alternative pathway. 39 However, the serum levels of sTCC were lower in subjects with SRC. 39 This is a confounding finding given that one would expect to find increased levels during the initial stages of the acute phase of the renal crisis.…”

Clinical significance of C4d deposition in renal tissues from patients with primary Sjögren’s syndrome—A preliminary study

“…In patients with LN, local immune complexes may be responsible for PTC C4d deposition as EDDs along the basement membrane of PTC were identified in 24/31 (77.4%) of patients with LN presenting PTC C4d deposition, whereas none of the patients with acute antibody-mediated rejection exhibited deposition(Li et al, 2007). In addition to autoantibodies, local shear stress on endothelial cells may play a role in the renal crisis in patients with scleroderma(Okroj et al, 2016;Yin et al, 2008), and PTC C4d correlated with an increased risk of renal failure(Batal et al, 2009). In our study, PTC C4d deposition was identified in 12 patients.…”

Особенности Поражения Почек При Системных Заболеваниях Соединительной Ткани

“…Преднизолон per os 1 мг/кг/сут максимум 80 мг + ММФ (1,5-3 г/сут) -6 месяцев или пульс-терапия ЦФ 500 мг в/в каждые 2 недели 3 месяца; пульс-терапия МП 0,75 г в/в 3 дняв начале терапии или ЦФ per os 1-1,5 мг/кг/сут, максимум 150 мг/сут - Результаты последних исследований демонстрируют, что гемодиализ требуется половине пациентов с СПК либо из-за перегрузки объемом вследствие снижения почечной функции или для контроля артериального давления при резистентной АГ [74]. При оптимальной терапии возможно прервать диализ у 16-55 % больных с СПК.…”

“…4, 2018 Погляд на проблему / Looking at the Рroblem является основной причиной гемодиализа и смерти у пациентов с РА [58]. Почечный амилоидоз при РА, обычно представленный АА-амилоидозом, возникает у пациентов с высокой активностью артрита, с длительным анамнезом и деструктивным по-Погляд на проблему / Looking at the Рroblem микроангиопатией, развитием неврологической симптоматики[74]. Группой экспертов Международного общества по изучению склеродермического почечного криза (ISRCS)[76] предложено диагностировать гипертензивный вариант СПК при наличии следующих критериев.…”