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Hypereosinophilic Syndrome Subtype Predicts Responsiveness to Glucocorticoids.

ABSTRACT: Glucocorticoids (GCs) are considered first-line treatment for platelet-derived growth factor ? (PDGFRA)-negative hypereosinophilic syndromes (HESs). Despite this, little is known about clinical predictors of GC responsiveness in HES.Knowledge of clinical and laboratory predictors of GC response before initiation of GC could lead to more rational selection of subjects with HES for whom earlier institution of second-line and alternative therapies would be appropriate.Response to GC, as defined by the reduction of the absolute eosinophil count to below 1000/mm3 and control of symptoms, was assessed by a retrospective chart review of subjects with PDGFRA-negative HES evaluated on an institutional review board-approved protocol. Demographic, clinical, and laboratory parameters obtained before institution of GC, as well as final diagnosis, were evaluated to determine predictors of GC response. Proportional odds models were used for univariate and multivariate assessment of predictors with permutation adjusted P values to correct for multiple comparisons.A total of 164 subjects with PDGFRA-negative HES were categorized according to GC response. Of them, 39% of the subjects responded to low dose (?10 mg) prednisone, 9% did not respond to GC, and the remainder (52%) had variable responses to GC. The HES subtype diagnosis was the best predictor of response to GC with myeloid forms and lymphocytic variants of HES being the least responsive to GC.In a large cohort of well-characterized subjects with HES, the odds of response to GC was predicted by HES subtype. Using this model, clinicians may more readily proceed to second-line agents in subjects with confirmed lymphocytic or myeloid forms of HES.

SUBMITTER: Khoury P

PROVIDER: S-EPMC5760470 | biostudies-other | 2018 Jan - Feb

REPOSITORIES: biostudies-other

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Hypereosinophilic Syndrome Subtype Predicts Responsiveness to Glucocorticoids.

Khoury Paneez P Abiodun Annalise O AO Holland-Thomas Nicole N Fay Michael P MP Klion Amy D AD

The journal of allergy and clinical immunology. In practice 20170727 1

<h4>Background</h4>Glucocorticoids (GCs) are considered first-line treatment for platelet-derived growth factor α (PDGFRA)-negative hypereosinophilic syndromes (HESs). Despite this, little is known about clinical predictors of GC responsiveness in HES.<h4>Objective</h4>Knowledge of clinical and laboratory predictors of GC response before initiation of GC could lead to more rational selection of subjects with HES for whom earlier institution of second-line and alternative therapies would be appro ...[more]

PMID: 28757367

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Project description:INTRODUCTION:An assay to determine glucocorticoid (GC) responsiveness in humans could be used to monitor GC non-responsiveness in states of GC insufficiency and could provide a tool to adapt GC treatment to individual patients. We propose an ex vivo assay to test GC responsiveness in peripheral leukocytes. The assay was evaluated in a human experimental model of surgery-induced inflammation. PATIENTS AND METHODS:Changes in expression of the GC-regulated genes GILZ, IL1R2, FKBP5, and HLA-DR and glucocorticoid receptor alpha (GR?) were determined by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) in peripheral leukocytes from surgical patients and healthy blood donors (total n=60) in response to low (1 nM) and high (1 µM) dexamethasone (DEX). The final selection of a suitable endogenous control gene was based on the studies of stability during DEX treatment and inflammation. Correlations between pre- and postoperative GC-induced gene expression, the postoperative systemic inflammatory and metabolic response (CRP, IL-6, white blood cell count, cytokines, resistin, free fatty acids, glucose, insulin, and adiponectin), and the clinical outcome were analyzed. The length of stay in the intensive care unit (ICU-LOS), the length of stay in the hospital, and postoperative complications were used to measure clinical outcome. RESULTS:When the blood donors were compared to the patients, there were no significant differences in the regulation of the genes in response to DEX, except for GR?. Preoperative, but not postoperative, gene regulation of GILZ and GR? was negatively correlated to ICU-LOS (P<0.05 and P<0.01, respectively). Preoperative GILZ and FKBP5 gene regulation was negatively correlated to postoperative systemic TNF? and MIP-1? levels. CONCLUSION:We suggest that this assay could be used to determine GC responsiveness. An alteration in preoperative GC responsiveness may be related to a patient's ability to recover from surgically induced inflammatory stress.

Dataset Information

Hypereosinophilic Syndrome Subtype Predicts Responsiveness to Glucocorticoids.

Publications

Hypereosinophilic Syndrome Subtype Predicts Responsiveness to Glucocorticoids.

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