Membrane attack complex (mac) deposition in lupus nephritis is associated with hypertension and poor clinical response to treatment

Shudan Wang, Ming Wu, Luis Chiriboga, Briana Zeck, H. Michael Belmont

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)256-262
Number of pages7
JournalSeminars in Arthritis and Rheumatism
Volume48
Issue number2
DOIs
StatePublished - Oct 2018
Externally publishedYes

Fingerprint

Complement Membrane Attack Complex
Lupus Nephritis
Hypertension
Biopsy
Therapeutics
Complement C9
Biomarkers
Staining and Labeling
Blood Pressure
Kidney
Proteinuria
Logistic Models
Immunohistochemistry

Keywords

  • Complement activation in lupus nephritis
  • Lupus nephritis
  • Lupus nephritis biomarker
  • Membrane attack complex

ASJC Scopus subject areas

  • Rheumatology
  • Anesthesiology and Pain Medicine

Cite this

Membrane attack complex (mac) deposition in lupus nephritis is associated with hypertension and poor clinical response to treatment. / Wang, Shudan; Wu, Ming; Chiriboga, Luis; Zeck, Briana; Belmont, H. Michael.

In: Seminars in Arthritis and Rheumatism, Vol. 48, No. 2, 10.2018, p. 256-262.

Research output: Contribution to journalArticle

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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.",
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AB - 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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