Anti-C1q antibodies in systemic lupus erythematosus

A-M Orbai; L Truedsson; G Sturfelt; O Nived; H Fang; G S Alarcón; C Gordon; Jt Merrill; P R Fortin; I N Bruce; D A Isenberg; D J Wallace; R Ramsey-Goldman; S-C Bae; J G Hanly; J Sanchez-Guerrero; A E Clarke; C B Aranow; S Manzi; M B Urowitz; D D Gladman; K C Kalunian; M I Costner; V P Werth; A Zoma; S Bernatsky; G Ruiz-Irastorza; M A Khamashta; S Jacobsen; J P Buyon; P Maddison; M A Dooley; R F Van Vollenhoven; E Ginzler; T Stoll; C Peschken; J L Jorizzo; J P Callen; S S Lim; B J Fessler; M Inanc; D L Kamen; A Rahman; K Steinsson; A G Franks Jr; L Sigler; S Hameed; N Pham; R Brey; M H Weisman; G McGwin Jr; L S Magder; M Petri

doi:10.1177/0961203314547791

Anti-C1q antibodies in systemic lupus erythematosus

Lupus. 2015 Jan;24(1):42-9. doi: 10.1177/0961203314547791. Epub 2014 Aug 14.

Authors

A-M Orbai¹, L Truedsson², G Sturfelt³, O Nived³, H Fang¹, G S Alarcón⁴, C Gordon⁵, Jt Merrill⁶, P R Fortin⁷, I N Bruce⁸, D A Isenberg⁹, D J Wallace¹⁰, R Ramsey-Goldman¹¹, S-C Bae¹², J G Hanly¹³, J Sanchez-Guerrero¹⁴, A E Clarke¹⁵, C B Aranow¹⁶, S Manzi¹⁷, M B Urowitz¹⁸, D D Gladman¹⁸, K C Kalunian¹⁹, M I Costner²⁰, V P Werth²¹, A Zoma²², S Bernatsky¹⁵, G Ruiz-Irastorza²³, M A Khamashta²⁴, S Jacobsen²⁵, J P Buyon²⁶, P Maddison²⁷, M A Dooley²⁸, R F Van Vollenhoven²⁹, E Ginzler³⁰, T Stoll³¹, C Peschken³², J L Jorizzo³³, J P Callen³⁴, S S Lim³⁵, B J Fessler⁴, M Inanc³⁶, D L Kamen³⁷, A Rahman³⁸, K Steinsson³⁹, A G Franks Jr²⁶, L Sigler¹, S Hameed¹, N Pham¹, R Brey⁴⁰, M H Weisman⁴¹, G McGwin Jr⁴, L S Magder⁴², M Petri⁴³

Affiliations

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 NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, UK.
⁹ Centre for Rheumatology, Research Division of Medicine, London, UK.
¹⁰ Cedars-Sinai Medical Center, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
¹¹ Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.
¹² Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea.
¹³ Division of Rheumatology, Departments of Medicine and Pathology Capital Health and Dalhousie University, Halifax, Nova Scotia, Canada.
¹⁴ Mount Sinai Hospital and University Health Network, Toronto, Ontario, Canada.
¹⁵ Divisions of Clinical Epidemiology and Rheumatology, McGill University Health Centre, Montreal, Quebec, Canada.
¹⁶ Feinstein Institute for Medical Research, Manhasset, NY, USA.
¹⁷ Department of Medicine, Division of Rheumatology, Allegheny Singer Research Institute, Allegheny General Hospital, Pittsburgh, PA, USA.
¹⁸ Toronto Western Hospital Toronto, Ontario, Canada.
¹⁹ Division of Rheumatology, Allergy and Immunology, UCSD School of Medicine, La Jolla, CA, USA.
²⁰ North Dallas Dermatology Associates, Dallas, TX, USA.
²¹ Philadelphia VA Medical Center and University of Pennsylvania, Philadelphia, PA, USA.
²² Lanarkshire Centre for Rheumatology and Hairmyres Hospital, East Kilbride, UK.
²³ Autoimmune Diseases Research Unit, Hospital Universitario Cruces Universidad del Pais Vasco, Barakaldo, Spain.
²⁴ Rayne Institute and St Thomas' Hospital London, UK.
²⁵ Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
²⁶ New York University, New York, NY, USA.
²⁷ Ysbyty Gwynedd, Bangor, UK.
²⁸ University of North Carolina, Chapel Hill, NC, USA.
²⁹ Karolinska University Hospital, Stockholm, Sweden.
³⁰ State University of New York, Downstate Medical Center, Brooklyn, NY, USA.
³¹ Kantonsspital Schaffhausen, Schaffhausen, Switzerland.
³² University of Manitoba Winnipeg, Manitoba, Canada.
³³ Wake Forest University, Winston-Salem, NC, USA.
³⁴ University of Louisville, Louisville, KY, USA.
³⁵ Emory University, Atlanta, GA, USA.
³⁶ Division of Rheumatology, Department of Internal Medicine, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
³⁷ Medical University of South Carolina, Charleston, SC, USA.
³⁸ NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, UK.
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.
⁴³ Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA MPetri@jhmi.edu.

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.

Keywords: Anti-dsDNA antibodies; renal lupus; systemic lupus erythematosus.

Publication types

Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Antibodies, Antinuclear / blood*
Case-Control Studies
Complement C1q / immunology*
Complement System Proteins / deficiency
Cross-Sectional Studies
DNA / immunology*
Female
Humans
Lupus Erythematosus, Systemic / ethnology
Lupus Erythematosus, Systemic / immunology*
Lupus Nephritis / ethnology
Lupus Nephritis / immunology
Male
Middle Aged
Proteinuria / blood
Rheumatic Diseases / immunology
Sensitivity and Specificity
Young Adult

Substances

Antibodies, Antinuclear
Complement C1q
Complement System Proteins
DNA

Abstract

Publication types

MeSH terms

Substances

Grants and funding