J Rheum Dis.  2021 Jul;28(3):150-158. 10.4078/jrd.2021.28.3.150.

Clinical and Genetic Risk Factors Associated With the Presence of Lupus Nephritis

Affiliations
  • 1Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea
  • 2Department of Rheumatology, Myongji Hospital, Hanyang University College of Medicine, Goyang, Korea
  • 3Hanyang University Institute for Rheumatology Research, Seoul, Korea
  • 4Division of Rheumatology, Department of Internal Medicine, Korea University Guro Hospital, Seoul, Korea
  • 5Department of Big Data Application, College of Social Economic & Interdisciplinary Studies, Hannam University, Daejeon, Korea
  • 6Departments of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul, Korea
  • 7Departments of Biology, Kyung Hee University, Seoul, Korea

Abstract


Objective
To elucidate whether clinical features and the weighted genetic risk score (wGRS) were associated with the presence of lupus nephritis (LN).
Methods
We retrospectively divided patients with systemic lupus erythematosus (SLE, n=1,078) into biopsy-proven LN (n=507) and non-LN groups (non-LN, n=571). Baseline clinical features, serologic markers, and the wGRS were collected. The wGRS was calculated from 112 non-human leukocyte antigen (non-HLA) loci and HLA-DRβ1 amino acid haplotypes for SLE. Associations among clinical features, wGRS, and the presence of LN were identified.
Results
In the multivariate analysis, patients with LN were younger at diagnosis (odds ratio [OR]=0.97, p<0.001), had more pleuritis (OR=2.44, p<0.001) and pericarditis (OR=1.62, p=0.029), had a higher detection rate of anti-double stranded deoxyribonucleic acid (anti-dsDNA antibodies, OR=2.22, p<0.001), anti-Smith antibodies (anti-Sm antibodies, OR=1.70, p=0.002), low level of complement (OR=1.37, p=0.043) and absence of antiphospholipid antibodies (aPL antibodies, OR=1.60, p=0.002), and had higher wGRS (OR=1.16, p=0.012). Mediation analysis suggested that anti-Sm antibodies and low complement could be mediators in the relationship between high wGRS and the presence of LN.
Conclusion
Onset age, pleuritis, pericarditis, several serologic markers, and wGRS were associated with the presence of LN. Anti-Sm antibodies and low complement appeared to mediate the indirect relationship between wGRS and the presence of LN.

Keyword

Systemic lupus erythematosus; Lupus nephritis; Genetic risk score; Associated factors
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