Shudan Wang1, Ming Wu2, Luis Chiriboga2, Briana Zeck2, H Michael Belmont3. 1. Medicine, Division of Rheumatology, NYU Langone Health, 301 East 17th St, Suite 1410, New York, NY 10003. Electronic address: shudanwang87@gmail.com. 2. Pathology, NYU Langone Health, New York, NY. 3. Medicine, Division of Rheumatology, NYU Langone Health, 301 East 17th St, Suite 1410, New York, NY 10003.
Abstract
OBJECTIVE: To study membrane attack complex in lupus nephritis as a potential biomarker for disease intensity and prognostic indicator for response to treatment. METHODS: Immunohistochemistry was performed using unconjugated, murine anti-human complement C9 on kidney biopsies from 30 SLE patients who fulfilled 4 ACR or SLICC criteria. Clinical parameters were assessed at time of biopsy, 6 and 12 months. RESULTS: 30 renal biopsies were obtained from patients with Class II (2), III (5), IV (8), V (5), III+V (8) and IV+V (2). 13/30 (43.3%) biopsies stained positive for glomerular C9. Patients with positive C9 had significantly higher blood pressure, trend towards lower C3, and male gender. There was no significant difference for ISN/RPN class, activity or chronicity indices between C9 positive and negative groups. 5/11 (45.5%) patients positive for C9 did not respond to therapy at 6 months compared with 2/15 (13.3%) patients negative for C9. C9 positive patients were more likely to be a non-responder at 6 months (OR = 5.4, 95% CI: 0.8, 36.4) compared to C9 negative patients. After adjusting for systolic blood pressure, compliance to treatment and proteinuria in a multivariate logistic model, C9 positive patients remained more likely to be non-responders (OR = 4.6, 95% CI: 0.3, 70.9). CONCLUSION: This study suggests that MAC deposition measured as C9 staining may be a biomarker for more intense disease and poor response to treatment in lupus nephritis. MAC staining may be useful in routine studies of lupus biopsies and identify patients at risk for aggressive disease who may be candidates for novel therapies targeting terminal complement pathway.
OBJECTIVE: To study membrane attack complex in lupus nephritis as a potential biomarker for disease intensity and prognostic indicator for response to treatment. METHODS: Immunohistochemistry was performed using unconjugated, murine anti-human complement C9 on kidney biopsies from 30 SLEpatients who fulfilled 4 ACR or SLICC criteria. Clinical parameters were assessed at time of biopsy, 6 and 12 months. RESULTS: 30 renal biopsies were obtained from patients with Class II (2), III (5), IV (8), V (5), III+V (8) and IV+V (2). 13/30 (43.3%) biopsies stained positive for glomerular C9. Patients with positive C9 had significantly higher blood pressure, trend towards lower C3, and male gender. There was no significant difference for ISN/RPN class, activity or chronicity indices between C9 positive and negative groups. 5/11 (45.5%) patients positive for C9 did not respond to therapy at 6 months compared with 2/15 (13.3%) patients negative for C9. C9 positive patients were more likely to be a non-responder at 6 months (OR = 5.4, 95% CI: 0.8, 36.4) compared to C9 negative patients. After adjusting for systolic blood pressure, compliance to treatment and proteinuria in a multivariate logistic model, C9 positive patients remained more likely to be non-responders (OR = 4.6, 95% CI: 0.3, 70.9). CONCLUSION: This study suggests that MAC deposition measured as C9 staining may be a biomarker for more intense disease and poor response to treatment in lupus nephritis. MAC staining may be useful in routine studies of lupus biopsies and identify patients at risk for aggressive disease who may be candidates for novel therapies targeting terminal complement pathway.
Authors: Sladjana Skopelja-Gardner; Lucrezia Colonna; Payton Hermanson; Xizhang Sun; Lena Tanaka; Joyce Tai; Yenly Nguyen; Jessica M Snyder; Charles E Alpers; Kelly L Hudkins; David J Salant; YuFeng Peng; Keith B Elkon Journal: J Immunol Date: 2020-04-01 Impact factor: 5.422
Authors: Jacob J E Koopman; Mieke F van Essen; Helmut G Rennke; Aiko P J de Vries; Cees van Kooten Journal: Front Immunol Date: 2021-02-11 Impact factor: 7.561
Authors: Anna Broder; H Michael Belmont; Shudan Wang; Ming Wu; Luis Chiriboga; Briana Zeck; Beatrice Goilav; Shuwei Wang; Alejandra Londono Jimenez; Chaim Putterman; Daniel Schwartz; James Pullman Journal: Lupus Sci Med Date: 2022-01
Authors: R Lande; R Palazzo; N Gestermann; C Jandus; M Falchi; F Spadaro; V Riccieri; E A James; A Butera; M Boirivant; L Feldmeyer; I Surbeck; J Di Lucca; F Stuber; F R Spinelli; E Botti; B Marinari; L Bianchi; R Pica; B Cerbelli; K Giannakakis; S E Auteri; I Daniels; L G Durrant; S Horstman; A Costanzo; P Romero; C Alessandri; F Conti; G Valesini; M Gilliet; C Chizzolini; L Frasca Journal: Sci Rep Date: 2020-04-03 Impact factor: 4.379