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Biomarkers for Refractory Lupus Nephritis: A Microarray Study of Kidney Tissue.

ABSTRACT: The prognosis of severe lupus nephritis (LN) is very different among individual patients. None of the current biomarkers can be used to predict the development of refractory LN. Because kidney histology is the gold standard for diagnosing LN, the authors hypothesize that molecular signatures detected in kidney biopsy tissue may have predictive value in determining the therapeutic response. Sixty-seven patients with biopsy-proven severely active LN by International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification III/IV were recruited. Twenty-three kidney tissue samples were used for RNA microarray analysis, while the remaining 44 samples were used for validation by real-time polymerase chain reaction (PCR) gene expression analysis. From hundreds of differential gene expressions in refractory LN, 12 candidates were selected for validation based on gene expression levels as well as relevant functions. The candidate biomarkers were members of the innate immune response molecules, adhesion molecules, calcium-binding receptors, and paracellular tight junction proteins. S100A8, ANXA13, CLDN19 and FAM46B were identified as the best kidney biomarkers for refractory LN, and COL8A1 was identified as the best marker for early loss of kidney function. These new molecular markers can be used to predict refractory LN and may eventually lead to novel molecular targets for therapy.

SUBMITTER: Benjachat T

PROVIDER: S-EPMC4490552 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Biomarkers for Refractory Lupus Nephritis: A Microarray Study of Kidney Tissue.

Benjachat Thitima T Tongyoo Pumipat P Tantivitayakul Pornpen P Somparn Poorichaya P Hirankarn Nattiya N Prom-On Santitham S Pisitkun Prapaporn P Leelahavanichkul Asada A Avihingsanon Yingyos Y Townamchai Natavudh N

International journal of molecular sciences 20150623 6

The prognosis of severe lupus nephritis (LN) is very different among individual patients. None of the current biomarkers can be used to predict the development of refractory LN. Because kidney histology is the gold standard for diagnosing LN, the authors hypothesize that molecular signatures detected in kidney biopsy tissue may have predictive value in determining the therapeutic response. Sixty-seven patients with biopsy-proven severely active LN by International Society of Nephrology/Renal Pat ...[more]

PMID: 26110394

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Project description:IntroductionLow-dose interleukin-2 (IL-2) selectively restores disturbances of regulatory T cells (Treg) and conventional T cells, resulting in the induction of remission in patients with systemic lupus erythematosus. However, to date no research has been carried out on the efficacy of low-dose IL-2 in the treatment of refractory lupus nephritis (LN). The aim of the study reported here was to investigate the renal response to low-dose IL-2 in patients with refractory LN.MethodsThe study population comprised ten patients with refractory LN who failed to achieve complete response or who had relapsed while being treated with at least two conventional immunosuppressive agents. One treatment cycle consisted of IL-2 at a dose of 1 million IU administered subcutaneously every other day for 2 weeks followed by a 2-week break. All patients received three cycles of IL-2 and were then followed up for another 12 weeks without any increase in the dose of previous immunosuppressive agents and steroids.ResultsOf the ten patients enrolled in the study, seven (70%) achieved ≥ 50% improvement in proteinuria at 12 weeks after initiating treatment with IL-2. Median proteinuria was significantly reduced by 50.3% at week 12, from 1.83 (interquartile range [IQR] 1.23-3.21) g/24 h at baseline to 0.91 (IQR 0.52-1.60) g/24 h at 12 weeks (P = 0.005). This was accompanied by a 71% reduction in urine erythrocytes, from 64/µl (IQR 24-102/µl) at baseline to 18/µl (IQR 2-20/µl) at 12 weeks (P = 0.018). Anti-dsDNA was decreased from 27.9 (IQR 7.6-40.28) IU/ml at baseline to 14.1 (IQR 7.3-20.12) IU/ml (P = 0.021) at week 12, while complements C3 and C4 were slightly increased (P = 0.445, P = 0.241, respectively). A significant expansion of Treg cells, from 9.3% at baseline to 16.6% at 12 weeks, was also found (P < 0.05). No serious adverse events occurred during the treatment period.ConclusionsLow-dose IL-2 therapy may have a promising role in the treatment of refractory LN as an alternative and safe therapeutic approach. It may be used as multi-target combination therapy in clinical practice.

Dataset Information

Biomarkers for Refractory Lupus Nephritis: A Microarray Study of Kidney Tissue.

Publications

Biomarkers for Refractory Lupus Nephritis: A Microarray Study of Kidney Tissue.

Similar Datasets

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