Four Systemic Lupus Erythematosus Subgroups, Defined by Autoantibodies Status, Differ Regarding HLA-DRB1 Genotype Associations and Immunological and Clinical Manifestations.

Autor: Diaz-Gallo LM; Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinksa University Hospital, Stockholm, Sweden.; Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden., Oke V; Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinksa University Hospital, Stockholm, Sweden.; Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden., Lundström E; Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinksa University Hospital, Stockholm, Sweden.; Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden., Elvin K; Department of Clinical Immunology and Transfusion Medicine, Unit of Clinical Immunology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden., Ling Wu Y; The Research Institute at Nationwide Children's Hospital, Columbus, Ohio.; Department of Microbiology and Immunology, Loyola University Chicago, lk, Illinois., Eketjäll S; Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Zickert A; Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinksa University Hospital, Stockholm, Sweden., Gustafsson JT; Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinksa University Hospital, Stockholm, Sweden., Jönsen A; Department of Clinical Sciences, Section of Rheumatology, Lund University, Skåne University Hospital, Lund, Sweden., Leonard D; Department of Medical Sciences, Section of Rheumatology, Uppsala University, Uppsala, Sweden., Birmingham DJ; Department of Internal Medicine, The Ohio State University, Columbus, Ohio., Nordmark G; Department of Medical Sciences, Section of Rheumatology, Uppsala University, Uppsala, Sweden., Bengtsson AA; Department of Clinical Sciences, Section of Rheumatology, Lund University, Skåne University Hospital, Lund, Sweden., Rönnblom L; Department of Medical Sciences, Section of Rheumatology, Uppsala University, Uppsala, Sweden., Gunnarsson I; Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinksa University Hospital, Stockholm, Sweden., Yu CY; The Research Institute at Nationwide Children's Hospital, Columbus, Ohio., Padyukov L; Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinksa University Hospital, Stockholm, Sweden.; Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden., Svenungsson E; Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinksa University Hospital, Stockholm, Sweden.
Jazyk: angličtina
Zdroj: ACR open rheumatology [ACR Open Rheumatol] 2022 Jan; Vol. 4 (1), pp. 27-39. Date of Electronic Publication: 2021 Oct 17.
DOI: 10.1002/acr2.11343
Abstrakt: Objective: The heterogeneity of systemic lupus erythematosus (SLE) constitutes clinical and therapeutical challenges. We therefore studied whether unrecognized disease subgroups can be identified by using autoantibody profiling together with HLA-DRB1 alleles and immunological and clinical data.
Methods: An unsupervised cluster analysis was performed based on detection of 13 SLE-associated autoantibodies (double-stranded DNA, nucleosomes, ribosomal P, ribonucleoprotein [RNP] 68, RNPA, Smith [Sm], Sm/RNP, Sjögren's syndrome antigen A [SSA]/Ro52, SSA/Ro60, Sjögren's syndrome antigen B [SSB]/La, cardiolipin [CL]-Immunoglobulin G [IgG], CL-Immunoglobulin M [IgM], and β 2 glycoprotein I [β 2 GPI]-IgG) in 911 patients with SLE from two cohorts. We evaluated whether each SLE subgroup is associated with HLA-DRB1 alleles, clinical manifestations (n = 743), and cytokine levels in circulation (n = 446).
Results: Our analysis identified four subgroups among the patients with SLE. Subgroup 1 (29.3%) was dominated by anti-SSA/Ro60/Ro52/SSB autoantibodies and was strongly associated with HLA-DRB1*03 (odds ratio [OR] = 4.73; 95% confidence interval [CI] = 4.52-4.94). Discoid lesions were more common for this disease subgroup (OR = 1.71, 95% CI = 1.18-2.47). Subgroup 2 (28.7%) was dominated by anti-nucleosome/SmRNP/DNA/RNPA autoantibodies and associated with HLA-DRB1*15 (OR = 1.62, 95% CI = 1.41-1.84). Nephritis was most common in this subgroup (OR = 1.61, 95% CI = 1.14-2.26). Subgroup 3 (23.8%) was characterized by anti-ß 2 GPI-IgG/anti-CL-IgG/IgM autoantibodies and a higher frequency of HLA-DRB1*04 compared with the other patients with SLE. Vascular events were more common in Subgroup 3 (OR = 1.74, 95% CI = 1.2-2.5). Subgroup 4 (18.2%) was negative for the investigated autoantibodies, and this subgroup was not associated with HLA-DRB1. Additionally, the levels of eight cytokines significantly differed among the disease subgroups.
Conclusion: Our findings suggest that four fairly distinct subgroups can be identified on the basis of the autoantibody profile in SLE. These four SLE subgroups differ regarding associations with HLA-DRB1 alleles and immunological and clinical features, suggesting dissimilar disease pathways.
(© 2021 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)
Databáze: MEDLINE
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