The molecular and cellular processes that lead to renal damage and to the heterogeneity of lupus nephritis (LN) are not well understood. We applied single-cell RNA sequencing (scRNA-seq) to renal biopsies from patients with LN and evaluated skin biopsies as a potential source of diagnostic and prognostic markers of renal disease. Type I interferon (IFN) response signatures in tubular cells and in keratinocytes distinguished patients with LN from healthy control subjects. Moreover, a high IFN response signature and fibrotic signature in tubular cells were each associated with failure to respond to treatment. Analysis of tubular cells from patients with proliferative, membranous, and mixed LN indicated pathways relevant to inflammation and fibrosis, which offer insight into their histological differences. In summary, we applied scRNA-seq to LN to deconstruct its heterogeneity and identify novel targets for personalized approaches to therapy.

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Objective We compared the prevalence and the clustering of the Metabolic Syndrome (MetS) components: obese body mass index (BMI ≥ 30 kg/m2), hypertriglyceridemia, low high-density lipids, hypertension and diabetes, in patients with psoriatic arthritis (PsA) and rheumatoid arthritis (RA) in the Consortium of Rheumatology Researchers of North America (CORRONA) registry. Methods We included CORRONA participants with the rheumatologist-confirmed clinical diagnoses of PsA and RA with complete data. We used a modified definition of MetS that did not include insulin resistance, waist circumference or blood pressure measurements. Logistic regression models were adjusted for age, sex and race. Results In the overall CORRONA population, the rates of diabetes and obesity were significantly higher in PsA compared with RA. In 294 PsA and 1162 RA participants who had lipids measured, the overall prevalence of MetS in PsA vs. RA was 27% vs. 19%. The odds ratio (OR) of MetS in PsA vs. RA was 1.44 (95% confidence interval (CI) 1.05 to 1.96), p=0.02. The prevalence of hypertriglyceridemia was higher in PsA compared with RA, 38% vs. 28%, OR 1.51 (95% CI 1.15 to 1.98), p=0.003. The prevalence of type II diabetes was also higher in PsA compared with RA (15% vs. 11%), OR 1.56 (95% CI 1.07 to 2.28), p=0.02, in the adjusted model. Similarly, higher rates of hypertriglyceridemia and diabetes were observed in the subgroup of PsA and RA patients with obese BMI. Conclusion PsA is associated with the higher rates of obesity, diabetes, and hypertriglyceridemia, compared with RA.

ObjectiveTo compare the performance characteristics of cell-bound complement (C4d) activation products (CBCAPS) on erythrocyte (EC4d) and B cells (BC4d) with antibodies to double-stranded DNA (anti-dsDNA) and complement C3 and C4 in systemic lupus erythematosus (SLE).MethodsThe study enrolled 794 subjects consisting of 304 SLE and a control group consisting of 285 patients with other rheumatic diseases and 205 normal individuals. Anti-dsDNA and other autoantibodies were measured using solid-phase immunoassays while EC4d and BC4d were determined using flow cytometry. Complement proteins were determined using immunoturbidimetry. Disease activity in SLE was determined using a non-serological Systemic Lupus Erythematosus Disease Activity Index SELENA Modification. A two-tiered methodology combining CBCAPS with autoantibodies to cellular and citrullinated antigens was also developed. Statistical analyses used area under receiver operating characteristic curves and calculations of area under the curve (AUC), sensitivity and specificity.ResultsAUC for EC4d (0.82±0.02) and BC4d (0.84±0.02) was higher than those yielded by C3 (0.73±0.02) and C4 (0.72±0.02) (p<0.01). AUC for CBCAPS was also higher than the AUC yielded by anti-dsDNA (0.79±0.02), but significance was only achieved for BC4d (p<0.01). The combination of EC4d and BC4d in multivariate testing methodology with anti-dsDNA and autoantibodies to cellular and citrullinated antigens yielded 80% sensitivity for SLE and specificity ranging from 70% (Sjogren's syndrome) to 92% (rheumatoid arthritis) (98% vs. normal). A higher proportion of patients with SLE with higher levels of disease activity tested positive for elevated CBCAPS, reduced complement and anti-dsDNA (p<0.03).ConclusionsCBCAPS have higher sensitivity than standard complement and anti-dsDNA measurements, and may help with the differential diagnosis of SLE in combination with other autoantibodies.