The pathogenesis, diagnosis and treatment of lupus nephritis

Schwartz, Noa; Goilav, Béatrice; Putterman, Chaim

doi:10.1097/bor.0000000000000089

Cited by 115 publications

(106 citation statements)

References 78 publications

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“…Relevant immunological markers were encountered in the majority of cases, with nearly 98% positive for antinuclear antibodies. Previous studies revealed that those who present at a younger age with severe nephritis and nervous system affections have poorer prognosis (2,27).…”

Section: Discussionmentioning

confidence: 99%

Childhood lupus nephritis: 12 years of experience from a developing country’s perspective

Samanta¹,

Nandi²,

Mondal³

et al. 2017

Eur J Rheumatol

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Objective: To assess the long-term outcome of lupus nephritis in children with systemic lupus erythematosus followed up over 12 years at a tertiary care teaching hospital in Eastern India. Material and Methods:This is a retrospective observational study of the clinicopathological presentation, management, and outcome in 46 children with lupus nephritis over a period of 12 years at a tertiary teaching hospital in Eastern India. Mortality was compared between different lupus classes and therapy groups with Kaplan-Meier analysis and log-rank testResults: The incidence of lupus nephritis was 58.97% [95% confidence interval (CI) 48.06%-59.89%] with the mean age at presentation being 10.2±2.43 years (range 5.5-14.5) years. Majority belonged to class IV (30.43%), followed by class II (26.91%), class III (23.91), and class V (8.70%). Outcome analysis of children with lupus nephritis over 12 years revealed that 24 (52.17%) achieved complete remission of disease activity, 5 attained partial remission, 4 continued to have active disease, 5 developed end-stage renal disease (ESRD), and 8 died. Overall mortality thus observed was 17.39% with septicemia in the background of ESRD being the commonest cause. No significant difference in mortality was observed between different lupus nephritis classes or therapy arm groups. Conclusion:The study throws light on various aspects of lupus nephritis and their long-term outcome patterns in children from developing countries such as India.

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Section: Discussionmentioning

confidence: 99%

Childhood lupus nephritis: 12 years of experience from a developing country’s perspective

Samanta¹,

Nandi²,

Mondal³

et al. 2017

Eur J Rheumatol

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“…Lupus nephritis is a major cause of morbidity and mortality in lupus patients, but diagnosis and monitoring remains challenging. Further, despite aggressive immunosuppressive therapy that is often complicated by serious adverse events, the incidence of end-stage kidney disease from lupus nephritis has not declined [7,8]. This emphasizes the need for a better understanding of the pathogenesis of lupus nephritis and the development of novel biomarkers to predict and monitor renal involvement in lupus patients.…”

Section: Introductionmentioning

confidence: 99%

Renal involvement in lupus is characterized by unique DNA methylation changes in naïve CD4+ T cells

Coit

Renauer

Jeffries

et al. 2015

Journal of Autoimmunity

116

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Systemic lupus erythematosus is a multi-system disease characterized by wide-spread DNA methylation changes. To identify epigenetic susceptibility loci for lupus nephritis, genome-wide DNA methylation changes in naïve CD4+ T cells were compared between two sets of lupus patients with and without a history of renal involvement. A total of 56 lupus patients (28 with renal involvement and 28 without renal involvement), and 56 age-, sex-, and ethnicity-matched healthy controls were included in our study. We identified 191 CG sites and 121 genes that were only differentially methylated in lupus patients with but not without a history of renal involvement. The tyrosine kinase gene TNK2 involved in cell trafficking and tissue invasion, and the phosphatase gene DUSP5 which dephosphorylates and inhibits the ERK signaling pathway, were among the most hypomethylated. Independent of disease activity, renal involvement is characterized by more robust demethylation in interferon regulated genes differentially methylated in both sets of lupus patients with and without renal involvement (fold change 1.4, P = 0.0014). The type-I interferon master regulator gene IRF7 is only hypomethylated in lupus patients with renal involvement. IRF-7 is an upstream transcription factor that regulates several loci demethylated only with renal involvement such as CD80, HERC5, IFI44, IRF7, ISG15, ISG20, ITGAX, and PARP12 (P = 1.78 × 10−6). Among the CG sites only hypomethylated with renal involvement, CG10152449 in CHST12 has a sensitivity of 85.7% and a specificity of 64.3% for stratifying lupus patients for a history of renal involvement (P = 0.0029). Our data identified novel epigenetic susceptibility loci that are differentially methylated with renal involvement in lupus. These loci will help better understand lupus nephritis, and provide a proof of principle for the potential applicability of specific methylation changes as predictors for specific organ involvement in lupus.

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“…Immune cells, cytokines, and epigenetic factors have all been recently implicated in LN pathogenesis (Schwartz et al, 2014). Primary IgAN chemical investigations have revealed that IgA1 molecules from patients differ in their glycosylation pattern compared with IgA1 from healthy subjects.…”

Section: Discussionmentioning

confidence: 99%

Decreased TIM-3 mRNA expression in peripheral blood mononuclear cells from nephropathy patients

Cai¹,

Liu²,

Qiao³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Increasing evidence shows that TIM-1 and TIM-3 influence chronic autoimmune diseases, and their expression levels in immune cells from nephritic patients are still unknown. Real-time transcription-polymerase chain reaction analysis was used to determine expression levels of TIM-1 and TIM-3 mRNA in peripheral blood mononuclear cells (PBMCs) from 36 patients with minimal change glomerulopathy (MCG), 65 patients with lupus nephritis (LN), 78 patients with IgA nephropathy (IgAN), 55 patients with membranous nephropathy (MN), 22 patients with crescentic glomerulonephritis (CGN), 26 patients with anaphylactoid purpura nephritis (APN), and 63 healthy controls. TIM-3 mRNA expression significantly decreased in PBMCs from nephritic patients (LN, P < 0.0001; MCG, P < 0.0001; MN, P = 0.0031; CGN, P = 0.0464; IgAN, P = 0.0002; APN, P = 0.0392) compared with healthy controls. In contrast, there was no significant difference in TIM-1 mRNA expression between the patients and the healthy X.Z. Cai et al. 6544©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (2): 6543-6548 (2015) controls. Our results suggest that insufficient expression of TIM-3 mRNA may be involved in the pathogenesis of nephropathy.

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The pathogenesis, diagnosis and treatment of lupus nephritis

Cited by 115 publications

References 78 publications

Childhood lupus nephritis: 12 years of experience from a developing country’s perspective

Childhood lupus nephritis: 12 years of experience from a developing country’s perspective

Renal involvement in lupus is characterized by unique DNA methylation changes in naïve CD4+ T cells

Decreased TIM-3 mRNA expression in peripheral blood mononuclear cells from nephropathy patients

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