Predicting Risk of Infection in Patients with Newly Diagnosed Multiple Myeloma: Utility of Immune Profiling
FRONTIERS IN IMMUNOLOGY
Authors: Teh, Benjamin W.; Harrison, Simon J.; Allison, Cody Charles; Slavin, Monica A.; Spelman, Tim; Worth, Leon J.; Thursky, Karin A.; Ritchie, David; Pellegrini, Marc
Abstract
Background: A translational study in patients with myeloma to determine the utility of immune profiling to predict infection risk in patients with hematological malignancy was conducted. Methods: Baseline, end of induction, and maintenance peripheral blood mononuclear cells from 40 patients were evaluated. Immune cell populations and cytokines released from 1 x 10(6) cells/ml cultured in the presence of a panel of stimuli (cytomegalovirus, influenza, S. pneumoniae, phorbol myristate acetate/ionomycin) and in media alone were quantified. Patient characteristics and infective episodes were captured from clinical records. Immunological variables associated with increased risk for infection in the 3-month period following sample collection were identified using univariate analysis (p < 0.05) and refined with multivariable analysis to define a predictive immune profile. Results: 525 stimulant samples with 19,950 stimulant-cytokine combinations across three periods were studied, including 61 episodes of infection. Mitogen-stimulated release of IL3 and IL5 were significantly associated with increased risk for subsequent infection during maintenance therapy. A lower Th1/Th2 ratio and higher cytokine response ratios for IL5 and IL13 during maintenance therapy were also significantly associated with increased risk for infection. On multivariable analysis, only IL5 in response to mitogen stimulation was predictive of infection. The lack of cytokine response and numerical value of immune cells were not predictive of infection. Conclusion: Profiling cytokine release in response to mitogen stimulation can assist with predicting subsequent onset of infection in patients with hematological malignancy during maintenance therapy.
Polymorphisms in the interleukin 4, interleukin 4 receptor and interleukin 13 genes and allergic phenotype: A case control study
ADVANCES IN MEDICAL SCIENCES
Authors: Narozna, Beata; Hoffmann, Aleksandra; Sobkowiak, Paulina; Schoneich, Natalia; Breborowicz, Anna; Szczepankiewicz, Aleksandra
Abstract
Purpose: Interleukin 4 (IL4), interleukin 4 receptor (IL4R) and interleukin 13 (IL13) play a key role in the pathogenesis of allergy and asthma development. IL4 and IL13 strongly influence bronchial hyperreactivity in response to allergen, airway remodeling, airway inflammation and airway smooth muscle proliferation. Both IL4 and IL13 exert biologic effect via interleukin 4 receptor. The aim of this study was to evaluate the impact of the polymorphisms within interleukin 4 (rs2243250, rs2227284), interleukin 4 receptor a chain (rs1805010, rs1805011) and interleukin 13 (rs20541) genes on the incidence of allergic phenotype in Polish pediatric population. Material/methods: We compared 177 asthmatic pediatric patients with 194 healthy children. Five polymorphisms within IL4, IL13 and IL4R alpha genes were analyzed. Genotypes of four polymorphisms (rs2243250, rs2227284, rs1805011, rs20541) were assigned by TaqMan SNP Genotyping Assays (Applied Biosystems), whereas rs18050100 polymorphism was established using PCR-RFLP method. Results: We observed an association of rs1805011 polymorphism of IL4R alpha gene with allergy (p = 0.021), mild asthma (p = 0.00005) and atopic dermatitis (p = 0.0056). Significant correlation was found between rs20541 in IL-13 gene and the positive skin prick test results (p = 0.029), along with rs2243250 polymorphism with clinical atopy (p = 0.033) and rs2227284 with total IgE levels (p = 0.00047). No associations were found for rs1805010. Conclusions: Our results indicate that rs1805011 polymorphism of IL4R alpha gene seems to influence allergy risk, especially mild asthma and atopic dermatitis predisposition in Polish children. Subgroup analysis of three other SNPs revealed possible influence on allergy development. (C) 2015 Medical University of Bialystok. Published by Elsevier Sp. z o.o. All rights reserved.