Dataset Information

A pathogenic IFNα, BLyS and IL-17 axis in Systemic Lupus Erythematosus patients.

ABSTRACT: This study aims to analyze in depth the role of IFNα in the upregulation of BLyS in different leukocyte populations and the possible relationship of these molecules with IL-17 and other pathogenic cytokines in SLE. Thus, IFNAR1 and membrane BLyS (mBLyS) expression was upregulated on various blood cell types from patients and closely correlated in all individuals. Moreover, BLyS serum levels associated positively with IFNα and IL-17A amounts, as well as with mBLyS on B cells and neutrophils. Interestingly, mBLyS on neutrophils was also correlated with IL-17A levels. Additionally, intracellular IL-17A expression was increased in both CD4(+) lymphocytes and neutrophils from patients, and IL-17(+)CD4(+) T cell frequency was associated with serum IFNα and IFNRA1 expression on B cells. Finally, in vitro assays support an IFNα role in the activation of Th17 cells in SLE. In conclusion, these data suggest that IFNα, BLyS and IL-17 could form a pathological axis in SLE, involving T and B lymphocytes, monocytes, DCs and neutrophils, which act in a vicious circle that encourage the preexisting inflammation and propagate the disease process.

SUBMITTER: Lopez P

PROVIDER: S-EPMC4742957 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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A pathogenic IFNα, BLyS and IL-17 axis in Systemic Lupus Erythematosus patients.

López Patricia P Rodríguez-Carrio Javier J Caminal-Montero Luis L Mozo Lourdes L Suárez Ana A

Scientific reports 20160205

This study aims to analyze in depth the role of IFNα in the upregulation of BLyS in different leukocyte populations and the possible relationship of these molecules with IL-17 and other pathogenic cytokines in SLE. Thus, IFNAR1 and membrane BLyS (mBLyS) expression was upregulated on various blood cell types from patients and closely correlated in all individuals. Moreover, BLyS serum levels associated positively with IFNα and IL-17A amounts, as well as with mBLyS on B cells and neutrophils. Inte ...[more]

PMID: 26847824

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Project description:IntroductionPatients with systemic lupus erythematosus (SLE) with B-lymphocyte stimulator (BLyS) levels ≥ 2 ng/mL are at increased risk of flare. A regression analysis was undertaken to identify routine clinical measures that correlate with BLyS ≥ 2 ng/mL. Efficacy and safety of belimumab 10 mg/kg were examined in patients with BLyS ≥ 2 ng/mL and < 2 ng/mL.MethodsData from BLISS-52 and -76 (N = 1684) were pooled post hoc. A univariate logistic regression was employed to identify factors predictive of baseline BLyS ≥ 2 ng/mL. Factors significant at the 0.05 level then entered a stepwise logistic regression as covariates. Efficacy endpoints included SLE responder index (SRI), ≥ 4-point reduction in Safety of Estrogens in Lupus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) and risk of severe flare over 52 weeks. Adverse events (AEs) were analyzed for each treatment arm and BLyS subgroup.ResultsBaseline predictors of BLyS ≥ 2 ng/mL included positive anti-Smith (≥ 15 U/mL), low complement (C) 3 (< 900 mg/L), anti-double-stranded DNA (anti-dsDNA) 80-200 and ≥ 200 IU/mL, immunosuppressant usage, proteinuria, elevated C-reactive protein (CRP), and low total lymphocyte count for all patients. Belimumab 10 mg/kg led to significantly greater SRI responses over 52 weeks versus placebo in both BLyS subgroups, though treatment differences were numerically greater at Week 52 in the BLyS ≥ 2 ng/mL group (24.1%, p < 0.0001) compared with BLyS < 2 ng/mL (8.2%, p = 0.0158). Results were similar for ≥ 4-point reduction in SELENA-SLEDAI. Risk of severe flare over 52 weeks was significantly reduced with belimumab 10 mg/kg versus placebo in the BLyS ≥ 2 ng/mL group (p = 0.0002). AEs were similar across treatment arms and BLyS subgroups.ConclusionsPositive anti-Smith, low C3, anti-dsDNA ≥ 80 IU/mL, immunosuppressant usage, proteinuria, elevated CRP, and low total lymphocyte count were predictors of BLyS ≥ 2 ng/mL. Monitoring these factors could identify patients with BLyS ≥ 2 ng/mL who are at risk of flare.

Dataset Information

A pathogenic IFNα, BLyS and IL-17 axis in Systemic Lupus Erythematosus patients.

Publications

A pathogenic IFNα, BLyS and IL-17 axis in Systemic Lupus Erythematosus patients.

Similar Datasets

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