Anti-C1q antibodies in systemic lupus erythematosus

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.

PMID: 25124676
PMCID: PMC4268323
DOI: 10.1177/0961203314547791

Multicenter Study

Anti-C1q antibodies in systemic lupus erythematosus

A-M Orbai et al. Lupus. 2015 Jan.

. 2015 Jan;24(1):42-9.

doi: 10.1177/0961203314547791. Epub 2014 Aug 14.

Authors

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.

PMID: 25124676
PMCID: PMC4268323
DOI: 10.1177/0961203314547791

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.

PubMed Disclaimer

References

1. Botto M, Walport MJ. C1q, autoimmunity and apoptosis. Immunobiology. 2002;205:395–406. - PubMed
1. Sturfelt G, Truedsson L. Complement in the immunopathogenesis of rheumatic disease. Nature reviews Rheumatology. 2012;8:458–68. - PubMed
1. Schejbel L, Skattum L, Hagelberg S, et al. Molecular basis of hereditary C1q deficiency--revisited: identification of several novel disease-causing mutations. Genes and immunity. 2011;12:626–34. - PubMed
1. Lood C, Gullstrand B, Truedsson L, et al. C1q inhibits immune complex-induced interferon-alpha production in plasmacytoid dendritic cells: a novel link between C1q deficiency and systemic lupus erythematosus pathogenesis. Arthritis and rheumatism. 2009;60:3081–90. - PubMed
1. Sturfelt G, Johnson U, Sjoholm AG. Sequential studies of complement activation in systemic lupus erythematosus. Scandinavian journal of rheumatology. 1985;14:184–96. - PubMed

Publication types

Actions
Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions
Actions

Grants and funding

LinkOut - more resources

Full Text Sources
Other Literature Sources
- The Lens - Patent Citations Database
- scite Smart Citations
Medical
- ClinicalTrials.gov
- MedlinePlus Health Information

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Anti-C1q antibodies in systemic lupus erythematosus

Affiliations

Anti-C1q antibodies in systemic lupus erythematosus

Authors

Affiliations

Abstract

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical