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

• Shin JM
• Kim D
• Kwon YC
• Ahn GY
• Lee J
• Park Y
• Lee YK
• Lee TH
• Park DJ
• Song YJ
• Ha E
• Kim K
• Bang SY
• Choi CB
• Lee HS
• Bae SC

• KMID: 2516951
• DOI: http://doi.org/10.4078/jrd.2021.28.3.150

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

Figure

• 

  Figure 1 Flow diagram of the study design. SLE: systemic lupus erythematosus, wGRS: weighted genetic risk score, ACR: American College of Rheum-atology, LN: lupus nephritis.

• 

  Figure 2 Conceptual model on three-step relationship between the exposure, mediator, and outcome. Step 1: association between the wGRS and serologic markers calculated by logistic regression analysis, step 2: association between the wGRS and lupus nephritis (LN) calculated by logistic regression analysis, step 3: association between serologic markers and LN calculated by logistic regression analysis, Sm: Smith, SEA: associated standard error for step 1 calculated by Sobel’s test, SEB: associated SE for step 3 calculated by Sobel’s test, SEA for anti-Sm antibodies: 0.066, SEA for low complement: 0.057, SEB for anti-Sm antibodies: 0.157, SEB for low complement: 0.141.

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