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Updated: Feb 15, 2026

Analyses of Proteinuria, Renal Infiltration of Leukocytes, and Renal Deposition of Proteins in Lupus-prone MRL/lpr Mice
Published on: June 8, 2022
Membrane attack complex (mac) deposition in lupus nephritis is associated with hypertension and poor clinical
Shudan Wang1, Ming Wu2, Luis Chiriboga2
1Medicine, Division of Rheumatology, NYU Langone Health, 301 East 17th St, Suite 1410, New York, NY 10003.
Insights
Membrane attack complex (MAC) deposition, indicated by C9 staining in kidney biopsies, may signal more severe lupus nephritis. This finding suggests C9 could predict poor treatment response in patients with this autoimmune kidney disease.
Area of Science:
- Nephrology
- Immunology
- Pathology
Background:
- Lupus nephritis is a severe complication of systemic lupus erythematosus (SLE).
- Identifying reliable biomarkers for disease activity and treatment response is crucial for managing lupus nephritis.
- The membrane attack complex (MAC) plays a role in inflammatory kidney diseases.
Purpose of the Study:
- To investigate the role of membrane attack complex (MAC) deposition in lupus nephritis.
- To evaluate MAC deposition, measured by C9 staining, as a biomarker for disease intensity.
- To assess MAC deposition as a prognostic indicator for treatment response in lupus nephritis.
Main Methods:
- Kidney biopsies from 30 SLE patients were analyzed using immunohistochemistry for C9 deposition.
- Clinical data, including blood pressure and treatment response, were collected at baseline, 6, and 12 months.
- Statistical analysis, including logistic regression, was used to correlate C9 positivity with clinical parameters and treatment outcomes.
Main Results:
- 43.3% of lupus nephritis biopsies showed positive glomerular C9 staining.
- C9-positive patients exhibited significantly higher blood pressure and a trend towards lower C3 levels.
- C9 positivity was associated with a higher likelihood of non-response to therapy at 6 months, even after multivariate adjustment.
Conclusions:
- Membrane attack complex (MAC) deposition, detected by C9 staining, may serve as a biomarker for disease severity in lupus nephritis.
- C9 staining could indicate a poorer response to treatment, identifying patients at risk for aggressive disease.
- MAC deposition assessment may aid in stratifying patients for targeted therapies, particularly those acting on the 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 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.
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