期刊
ACR OPEN RHEUMATOLOGY
卷 4, 期 1, 页码 27-39出版社
WILEY
DOI: 10.1002/acr2.11343
关键词
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类别
资金
- Swedish Research Council--Ventenskapsradet [2014-33867, 2018-02535, 2018-02399]
- King Gustaf V 80th Birthday Fund-Stiftelsen Konung Gustaf V:s 80--arsfond [FAI-2017-0390, FAI-2018-0518, FAI-2019-0597, FAI-2018-0478]
- Swedish Heart--Lung Foundation--Hjart-Lungfonden [20170257]
- Swedish Rheumatism Association--Reumatikerforbundet [R-739631, 861801, R-932138, 930005]
- Ulla och Gustaf af Uggla stiftelse [2018-02670, 2020-02395]
- Swedish Society of Medicine
- Ingegerd Johansson Donation--Svenska Lakaresallskapet [SLS-713911, SLS-936449]
- StockholmCounty Council--Stockholms Lans Landsting [20170038]
- Swedish Research Council [2018-02535, 2018-02399] Funding Source: Swedish Research Council
Our study identified four distinct subgroups among patients with SLE based on autoantibody profiles, which differ in associations with HLA-DRB1 alleles and immunological and clinical features, indicating diverse disease pathways.
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, Sjogren's syndrome antigen A [SSA]/Ro52, SSA/Ro60, Sjogren's syndrome antigen B [SSB]/La, cardiolipin [CL]-Immunoglobulin G [IgG], CL-Immunoglobulin M [IgM], and beta(2) glycoprotein I [beta(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.
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