Racial variability in immune responses only partially explains differential systemic sclerosis disease severity

Kamini E Kuchinad; Ji Soo Kim; Adrianne Woods; Gwen Leatherman; Laura Gutierrez-Alamillo; Maureen D Mayes; Robyn Domsic; Paula S Ramos; Richard M Silver; John Varga; Lesley Ann Saketkoo; Suzanne Kafaja; Victoria K Shanmugan; Jessica Gordon; Lorinda Chung; Elana J Bernstein; Pravitt Gourh; Francesco Boin; Daniel L Kastner; Scott L Zeger; Livia Casciola-Rosen; Fredrick M Wigley; Ami A Shah

doi:10.1136/ard-2023-225458

Racial variability in immune responses only partially explains differential systemic sclerosis disease severity

Ann Rheum Dis. 2024 Oct 21;83(11):1513-1521. doi: 10.1136/ard-2023-225458.

Authors

Kamini E Kuchinad¹, Ji Soo Kim¹, Adrianne Woods¹, Gwen Leatherman¹, Laura Gutierrez-Alamillo¹, Maureen D Mayes², Robyn Domsic³, Paula S Ramos⁴, Richard M Silver⁵, John Varga⁶, Lesley Ann Saketkoo^{7

8}, Suzanne Kafaja⁹, Victoria K Shanmugan¹⁰, Jessica Gordon¹¹, Lorinda Chung¹², Elana J Bernstein¹³, Pravitt Gourh¹⁴, Francesco Boin¹⁵, Daniel L Kastner¹⁶, Scott L Zeger¹⁷, Livia Casciola-Rosen¹, Fredrick M Wigley¹, Ami A Shah¹⁸

Affiliations

¹ Division of Rheumatology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
² Division of Rheumatology and Clinical Immunogenetics, The University of Texas Health Science Center John P and Katherine G McGovern Medical School, Houston, Texas, USA.
³ Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
⁴ Department of Medicine, Division of Rheumatology, Medical University of South Carolina, Charleston, South Carolina, USA.
⁵ Division of Rheumatology and Immunology, Medical University of South Carolina, Charleston, South Carolina, USA.
⁶ Division of Rheumatology, University of Michigan, Ann Arbor, Michigan, USA.
⁷ New Orleans Scleroderma and Sarcoidosis Patient Care and Research Center, Tulane University School of Medicine, New Orleans, Louisiana, USA.
⁸ Section of Pulmonary Medicine, University Medical Center - Comprehensive Pulmonary Hypertension Center and Interstitial Lung Disease Clinic Programs, Louisiana State University School of Medicine, New Orleans, Louisiana, USA.
⁹ Internal Medicine/Division of Rheumatology, University of California Los Angeles, Los Angeles, California, USA.
¹⁰ Office of Autoimmune Disease Research, National Institute of Health, Bethesda, Maryland, USA.
¹¹ Department of Rheumatology, Department of Medicine, Hospital for Special Surgery, New York, New York, USA.
¹² Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, California, USA.
¹³ Division of Rheumatology, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA.
¹⁴ NIAMS, National Institutes of Health, Bethesda, Maryland, USA.
¹⁵ Division of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, California, USA.
¹⁶ National Human Genome Research Institute Division of Intramural Research, Bethesda, Maryland, USA.
¹⁷ Biostatistics, Johns Hopkins University, Baltimore, Maryland, USA.
¹⁸ Division of Rheumatology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA Ami.Shah@jhmi.edu.

PMID: 39019570
DOI: 10.1136/ard-2023-225458

Abstract

Objective: To understand if autoantibodies account for racial variation in disease severity, we compared autoantibody distribution and associated phenotype between self-identified black and white systemic sclerosis (SSc) patients.

Methods: 803 black and 2178 white SSc patients had systematic testing for autoantibodies using Euroimmun (centromere (ACA), RNA-polymerase III (POLR3), Scl70, PM/Scl, NOR90, Th/To, Ku, U3RNP and Ro52) and commercial ELISA (U1RNP). In this observational study, logistic regression was performed to assess the association between self-identified race and outcomes, adjusting for autoantibodies. To estimate whether the effect of race was mediated by autoantibody status, race coefficients from multivariate models including and excluding autoantibodies were compared.

Results: Anti-Scl70, anti-U1RNP, anti-U3RNP, anti-Th/To, anti-Ku and anti-NOR90 were more common in the black cohort than in the white cohort, which was enriched for ACA, anti-POLR3 and anti-PM/Scl. Black individuals had a higher prevalence of severe Raynaud's, skin, lung, gastrointestinal and renal disease whereas white individuals had a higher prevalence of severe heart and muscle disease. Adjusting for autoantibodies decreased the effect of race on outcome for telangiectasias, forced vital capacity <70%, pulmonary hypertension and severe lung, heart, muscle and gastrointestinal disease by 11%-44% and increased the association between race and renal crisis and severe kidney disease by 37%-52%.

Conclusions: This study is the largest systematic analysis of autoantibody responses in a geographically diverse population of black SSc patients. Black and white individuals with SSc have distinct autoantibody profiles. Autoantibodies explain only a fraction of the effect of race on clinical outcomes, suggesting other factors contribute to disparate outcomes between these groups.

Keywords: Autoantibodies; Epidemiology; Risk Factors; Systemic Sclerosis.

Publication types

Observational Study

MeSH terms

Adult
Aged
Autoantibodies* / blood
Autoantibodies* / immunology
Black or African American
Female
Humans
Male
Middle Aged
Scleroderma, Systemic* / ethnology
Scleroderma, Systemic* / immunology
Severity of Illness Index*
White

Substances

Autoantibodies

Grants and funding

R01 AR073208/AR/NIAMS NIH HHS/United States