ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1675

SLE Comprises Four Immune-Phenotypes, Which Differ Regarding HLA-DRB1 and Clinical Associations

Lina Marcela Diaz Gallo1, Emeli Lundström1, Vilija Oke1, Kerstin Elvin2, Yee Ling Wu3, Johanna Gustafsson1, Andreas Jönsen4, Dag Leonard5, Agneta Zickert6, Gunnel Nordmark7, Anders A. Bengtsson4, Johanna K Sandling7, Lars Rönnblom8, Iva Gunnarsson1, CHACK-YUNG Yu9, Leonid Padyukov10 and Elisabet Svenungsson10, 1Department of Medicine, Rheumatology Unit, Department of Medicine Solna, Rheumatology Unit, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden, Stockholm, Sweden, 2Dept. of Clinical Immunology and Transfusion Medicine, Unit of Clinical Immunology, Department of Medicine Solna, Rheumatology Unit, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden, Stockholm, Sweden, 3The Research Institute at Nationwide Children's Hospital and The Ohio State University, Columbus, OH, 4Lund University, Department of Clinical Sciences, Rheumatology, Lund, Sweden, 5Rheumatology and Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Sweden, Uppsala, Sweden, 6Department of Medicine, Rheumatology Unit, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden, 7Department of Medical Sciences, Section of Rheumatology, Uppsala University, Uppsala, Sweden, Uppsala, Sweden, 8Medical Sciences, Rheumatology clinic, Uppsala, Sweden, 9Center for Molecular and Human Genetics, The Research Institute at Nationwide Children's Hospital, Columbus, OH, 10Department of Medicine Solna, Rheumatology Unit, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden, Stockholm, Sweden

Meeting: ACR/ARHP Annual Meeting 2017

Date of first publication: September 18, 2017

Keywords: ,

Session Information

Date: Monday, November 6, 2017

Title: Systemic Lupus Erythematosus – Human Etiology and Pathogenesis Poster I

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: SLE is a remarkably heterogeneous disease including diverging clinical symptoms, autoantibodies and genetic susceptibility. Hitherto unrecognized patterns may define sub-phenotypes with different pathogenesis and specific treatment needs. Based on autoantibody profile we therefore investigated phenotypic clusters and explored cluster associations with clinical manifestations and one of the most important genetic risk factors for SLE, HLA-DRB1alleles.

Methods: 908 SLE patients (fulfilling 1982 ACR criteria) of European Caucasian origin and 3654 age- gender- and ethnicity-matched healthy controls (HC) were included. We determined the occurrence of 13 autoantibodies: dsDNA, nucleosomes, ribosomal P, RNP68, RNPA, Sm, Sm/RNP, SSA52, SSA60, SSB, aCL-IgG/IgM and ab2GP1. HLA-DRB1 typing was performed by sequence-specific primer polymerase chain reaction assay. Cluster analysis was done using Gower distance matrix, followed by partition around medoids cluster calculation and Silhouette metric for number of clusters validation. Chi-square test, odds ratios (OR), 95% confidence intervals and false discovery rate p value (p) were calculated for the association tests (within brackets).

Results: Four (1-4) clusters were defined based on autoantibody occurrence.

1) 29%, dominated by anti-SSA52/60/SSB positivity is strongly associated with HLA-DRB1*03 when compared to HC (4.1[3.4-4.9] p=6.4E-56) and other clusters (2.9[93.3-3.6] p=1.1E-19). Discoid lesions were more common vs. other clusters (1.8[1.3-2.6] p= 0.02).

2) 29 %, dominated by anti-SmRNP/Sm/DNA/RNPA/RNP68/nucleosome, was specifically associated with HLA-DRB1*15 when compared to HC (1.7[1.6-2.1] p=5.7E-6) and other clusters (1.5[1.1-1.9] p=0.01). Nephritis was common vs. other clusters (1.9[1.4-2.7) p= 2.E-03)

3) 24 %, dominated by anti-B2GP1/aCL-IgG/IgM, was associated with HLA-DRB1*04 when compared with other clusters (1.8[1.4-2.4] p=2E-4). More thrombotic events vs. other clusters were observed in this group (1.84 [1.3-2.6] p=0.01)

4) 18 % was negative for the 13 tested autoantibodies and was not associated with any specific HLA-DRB1 alleles and it was not associated as risk factor for any of the evaluated clinical manifestations.

Conclusion: We demonstrate that immune-phenotypes/clusters in SLE can fit into a frame of HLA-DRB1 alleles and that the overall association between SLE and HLA-DRB1*03 and HLA-DRB1*15 seems to be driven mainly by clusters 1 and 2, respectively. We also confirm previous observations that autoantibody clusters associate with clinical symptoms. We believe that these results could be used to redefine SLE, determine predictive biomarkers and inclusion criteria for clinical trials.

Disclosure: L. M. Diaz Gallo, None; E. Lundström, None; V. Oke, None; K. Elvin, None; Y. L. Wu, None; J. Gustafsson, None; A. Jönsen, None; D. Leonard, None; A. Zickert, None; G. Nordmark, None; A. A. Bengtsson, None; J. K. Sandling, None; L. Rönnblom, None; I. Gunnarsson, None; C. Y. Yu, None; L. Padyukov, None; E. Svenungsson, None.

To cite this abstract in AMA style:

Diaz Gallo LM, Lundström E, Oke V, Elvin K, Wu YL, Gustafsson J, Jönsen A, Leonard D, Zickert A, Nordmark G, Bengtsson AA, Sandling JK, Rönnblom L, Gunnarsson I, Yu CY, Padyukov L, Svenungsson E. SLE Comprises Four Immune-Phenotypes, Which Differ Regarding HLA-DRB1 and Clinical Associations [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/sle-comprises-four-immune-phenotypes-which-differ-regarding-hla-drb1-and-clinical-associations/. Accessed .

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