Observational Study

. 2024 Oct 21;83(11):1513-1521.

doi: 10.1136/ard-2023-225458.

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

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
PMCID: PMC11875133
DOI: 10.1136/ard-2023-225458

Observational Study

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

Kamini E Kuchinad et al. Ann Rheum Dis. 2024.

. 2024 Oct 21;83(11):1513-1521.

doi: 10.1136/ard-2023-225458.

Authors

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
PMCID: PMC11875133
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.

PubMed Disclaimer

Conflict of interest statement

Competing interests: RD received consulting fees from CSL Behring and Astra-Zeneca. LAS received grant funding from Horizon Pharmaceuticals, aTyr Pharmaceuticals and Kinevant Pharmaceuticals and honoraria from Janssen Pharmaceuticals. She served on the data safety monitoring board for Argenx Pharmaceuticals. LC received grant funding from Boehringer Ingelheim and consulting fees from Kyverna, Eicos Sciences, Genentech, IgM Biosciences, Lilly. She participated in an advisory capacity for Mitsubishi Tanabe and Janssen. FB received honoraria from Janssen. RMS received grant funding from Boehringer Ingelheim, Merck and Amgen; he is the CEO of FibroBiologics. JV received consulting fees from TeneoBio, and Conquest; he serves on the data safety monitoring board for Conquest. MDM received grant funding from Prometheus Biosciences, Mitsubishi Tanabe, Boehringer Ingelheiem, Eicos, Corbus and Horizon Pharmaceuticals. She received consulting fees from Cabaletta Pharmaceuticals; she served on the advisory board for Mitsubishi Tanabe and Eicos Sciences. AS has grant support from Kadmon, Arena Pharmaceuticals, Medpace and Eicos Sciences.

Figures

**Figure 1.. Comparison of autoantibody distribution between Black and White Individuals in the GRASP and Johns Hopkins Scleroderma Cohorts.**
Numbers do not add up to 100% due to autoantibody overlap. ACA=anti-centromere antibody; POLR3, anti-RNA polymerase III; anti-Scl70, anti-topoisomerase; AB neg, individuals that tested negative by EBO and U1RNP antibody assays. Autoantibody frequency was compared using Chi-squared tests. * p<0.05, ** p<0.005, *** p<0.0005.

**Figure 2.. Coexistence of autoantibodies in the GRASP and Johns Hopkins Scleroderma Cohorts.**
Each box represents the percentage if individuals with a designated antibody overlap. The 45-degree line illustrates patients who are monospecific for a given antibody. The total frequency of positivity for a given autoantibody is determined by the sum of all values in a given column. ACA, anti-centromere antibody; POLR3, anti-RNA polymerase III; anti-Scl70, anti-topoisomerase 1.

See this image and copyright information in PMC

References

1. Van Den Hoogen F, Khanna D, Fransen J, et al. 2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League against Rheumatism collaborative initiative. Arthritis Rheum. 2013;65(11):2737–2747. doi:10.1002/ART.38098 - DOI - PMC - PubMed
1. Masi AT. Preliminary criteria for the classification of systemic sclerosis (scleroderma). Subcommittee for scleroderma criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee. Arthritis Rheum. 1980;23(5):581–590. doi:10.1002/ART.1780230510 - DOI - PubMed
1. Morgan ND, Shah AA, Mayes MD, et al. Clinical and serological features of systemic sclerosis in a multicenter African American cohort: Analysis of the genome research in African American scleroderma patients clinical database. Medicine. 2017;96(51). doi:10.1097/MD.0000000000008980 - DOI - PMC - PubMed
1. Gelber AC, Manno RL, Shah AA, et al. Race and Association With Disease Manifestations and Mortality in Scleroderma: A 20-Year Experience at the Johns Hopkins Scleroderma Center and Review of the Literature. Medicine. 2013;92(4):191. doi:10.1097/MD.0B013E31829BE125 - DOI - PMC - PubMed
1. Laing TJ, Gillespie BW, Toth MB, et al. Racial differences in scleroderma among women in Michigan. Arthritis Rheum. 1997;40(4):734–742. doi:10.1002/ART.1780400421 - DOI - PubMed

Publication types

Actions

MeSH terms

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

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

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Research Materials

Miscellaneous