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

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.

Keywords: Associated factors; Genetic risk score; Lupus nephritis; Systemic lupus erythematosus.

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.