Anti-C1q antibodies in systemic lupus erythematosus

Author:

Orbai A-M1,Truedsson L2,Sturfelt G3,Nived O3,Fang H1,Alarcón G S4,Gordon C5,Merrill JT6,Fortin P R7,Bruce I N89,Isenberg D A10,Wallace D J11,Ramsey-Goldman R12,Bae S-C13,Hanly J G14,Sanchez-Guerrero J15,Clarke A E16,Aranow C B17,Manzi S18,Urowitz M B19,Gladman D D19,Kalunian K C20,Costner M I21,Werth V P22,Zoma A23,Bernatsky S16,Ruiz-Irastorza G24,Khamashta M A25,Jacobsen S26,Buyon J P27,Maddison P28,Dooley M A29,Van Vollenhoven R F30,Ginzler E31,Stoll T32,Peschken C33,Jorizzo J L34,Callen J P35,Lim S S36,Fessler B J4,Inanc M37,Kamen D L38,Rahman A9,Steinsson K39,Franks A G27,Sigler L1,Hameed S1,Pham N1,Brey R40,Weisman M H41,McGwin G4,Magder L S42,Petri M1

Affiliation:

1. Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

2. Department of Laboratory Medicine, Section of Microbiology, Immunology and Glycobiology, Lund University, Lund, Sweden

3. Department of Rheumatology, Skåne University Hospital, Lund, Sweden

4. Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, USA

5. Rheumatology Research Group, School of Immunity and Infection, College of Medical and Dental Sciences University of Birmingham, Birmingham, UK

6. Department of Clinical Pharmacology, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA

7. Division of Rheumatology, Department of Medicine, Centre Hospitalier Universitaire (CHU) de Québec Axe Maladies Infectieuses et Immunitaires, CRCHU de Québec, Université Laval, Quebec City, Quebec, Canada

8. Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Institute of Inflammation and Repair, Manchester Academic Health Sciences Centre, The University of Manchester, Manchester, UK

9. NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, UK

10. Centre for Rheumatology, Research Division of Medicine, London, UK

11. Cedars-Sinai Medical Center, David Geffen School of Medicine, University of California, Los Angeles, CA, USA

12. Northwestern University, Feinberg School of Medicine, Chicago, IL, USA

13. Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea

14. Division of Rheumatology, Departments of Medicine and Pathology Capital Health and Dalhousie University, Halifax, Nova Scotia, Canada

15. Mount Sinai Hospital and University Health Network, Toronto, Ontario, Canada

16. Divisions of Clinical Epidemiology and Rheumatology, McGill University Health Centre, Montreal, Quebec, Canada

17. Feinstein Institute for Medical Research, Manhasset, NY, USA

18. Department of Medicine, Division of Rheumatology, Allegheny Singer Research Institute, Allegheny General Hospital, Pittsburgh, PA, USA

19. Toronto Western Hospital Toronto, Ontario, Canada

20. Division of Rheumatology, Allergy and Immunology, UCSD School of Medicine, La Jolla, CA, USA

21. North Dallas Dermatology Associates, Dallas, TX, USA

22. Philadelphia VA Medical Center and University of Pennsylvania, Philadelphia, PA, USA

23. Lanarkshire Centre for Rheumatology and Hairmyres Hospital, East Kilbride, UK

24. Autoimmune Diseases Research Unit, Hospital Universitario Cruces Universidad del Pais Vasco, Barakaldo, Spain

25. Rayne Institute and St Thomas' Hospital London, UK

26. Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark

27. New York University, New York, NY, USA

28. Ysbyty Gwynedd, Bangor, UK

29. University of North Carolina, Chapel Hill, NC, USA

30. Karolinska University Hospital, Stockholm, Sweden

31. State University of New York, Downstate Medical Center, Brooklyn, NY, USA

32. Kantonsspital Schaffhausen, Schaffhausen, Switzerland

33. University of Manitoba Winnipeg, Manitoba, Canada

34. Wake Forest University, Winston-Salem, NC, USA

35. University of Louisville, Louisville, KY, USA

36. Emory University, Atlanta, GA, USA

37. Division of Rheumatology, Department of Internal Medicine, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey

38. Medical University of South Carolina, Charleston, SC, USA

39. Landspitali University Hospital, Reykjavik, Iceland

40. University of Texas Health Science Center, San Antonio, TX, USA

41. Cedars-Sinai Medical Center, Los Angeles, CA, USA

42. Department of Epidemiology and Public Health, University of Maryland, Baltimore, MD, USA

Abstract

Objective Anti-C1q has been associated with systemic lupus erythematosus (SLE) and lupus nephritis in previous studies. We studied anti-C1q specificity for SLE (vs rheumatic disease controls) and the association with SLE manifestations in an international multicenter study. Methods Information and blood samples were obtained in a cross-sectional study from patients with SLE ( n = 308) and other rheumatologic diseases ( n = 389) from 25 clinical sites (84% female, 68% Caucasian, 17% African descent, 8% Asian, 7% other). IgG anti-C1q against the collagen-like region was measured by ELISA. Results Prevalence of anti-C1q was 28% (86/308) in patients with SLE and 13% (49/389) in controls (OR = 2.7, 95% CI: 1.8–4, p < 0.001). Anti-C1q was associated with proteinuria (OR = 3.0, 95% CI: 1.7–5.1, p < 0.001), red cell casts (OR = 2.6, 95% CI: 1.2–5.4, p = 0.015), anti-dsDNA (OR = 3.4, 95% CI: 1.9–6.1, p < 0.001) and anti-Smith (OR = 2.8, 95% CI: 1.5–5.0, p = 0.01). Anti-C1q was independently associated with renal involvement after adjustment for demographics, ANA, anti-dsDNA and low complement (OR = 2.3, 95% CI: 1.3–4.2, p < 0.01). Simultaneously positive anti-C1q, anti-dsDNA and low complement was strongly associated with renal involvement (OR = 14.9, 95% CI: 5.8–38.4, p < 0.01). Conclusions Anti-C1q was more common in patients with SLE and those of Asian race/ethnicity. We confirmed a significant association of anti-C1q with renal involvement, independent of demographics and other serologies. Anti-C1q in combination with anti-dsDNA and low complement was the strongest serological association with renal involvement. These data support the usefulness of anti-C1q in SLE, especially in lupus nephritis.

Publisher

SAGE Publications

Subject

Rheumatology

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