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IL-4 polymorphism influences susceptibility to Pneumocystis jirovecii pneumonia in HIV-positive patients


Wójtowicz, Agnieszka; Bibert, Stéphanie; Taffé, Patrick; Bernasconi, Enos; Furrer, Hansjakob; Günthard, Huldrych F; Hoffmann, Matthias; Osthoff, Michael; Cavassini, Matthias; Bochud, Pierre-Yves; Swiss HIV Cohort Study (2019). IL-4 polymorphism influences susceptibility to Pneumocystis jirovecii pneumonia in HIV-positive patients. AIDS, 33(11):1719-1727.

Abstract

OBJECTIVES
Pneumocystis jirovecii pneumonia (PJP) is an important cause of morbidity and mortality in HIV-positive patients. Polymorphisms in immune genes are increasingly reported to influence susceptibility to fungal infections. We analysed the role of 21 single nucleotide polymorphisms from 19 candidate genes on PJP development in patients from the Swiss HIV Cohort Study.
DESIGN AND METHODS
The analysis included patients with a nadir CD4 T-cell count less than 200 cells/μl, divided into a discovery (N = 1645) and a replication (N = 1861) cohort. The associations were analysed by using cumulative incidence curves as well as competing risk regression over 18 years, starting from the estimated date of HIV infection, considering death a competing risk, with censoring at lost follow-up, and assuming the dominant mode of inheritance.
RESULTS
The minor allele of rs2243250 in IL-4 was associated with the risk of PJP in the discovery cohort (cumulative incidence 0.18 versus 0.12, P = 0.002). This association was replicated in the validation cohort (0.16 versus 0.12, P = 0.02). It was still significant in multivariate models, adjusted for HIV transmission mode, viral load, CD4 T cells slope, age, antiretroviral therapy, tobacco smoking, hepatitis C virus coinfection, year of cohort entry and PJP prophylaxis (global subhazard ratio 1.42, 95% confidence interval 1.17-1.73, P = 0.0004).
CONCLUSION
Our data suggest rs2243250, a single nucleotide polymorphism known to influence IL-4 production, is associated with susceptibility to PJP in HIV-positive patients.

Abstract

OBJECTIVES
Pneumocystis jirovecii pneumonia (PJP) is an important cause of morbidity and mortality in HIV-positive patients. Polymorphisms in immune genes are increasingly reported to influence susceptibility to fungal infections. We analysed the role of 21 single nucleotide polymorphisms from 19 candidate genes on PJP development in patients from the Swiss HIV Cohort Study.
DESIGN AND METHODS
The analysis included patients with a nadir CD4 T-cell count less than 200 cells/μl, divided into a discovery (N = 1645) and a replication (N = 1861) cohort. The associations were analysed by using cumulative incidence curves as well as competing risk regression over 18 years, starting from the estimated date of HIV infection, considering death a competing risk, with censoring at lost follow-up, and assuming the dominant mode of inheritance.
RESULTS
The minor allele of rs2243250 in IL-4 was associated with the risk of PJP in the discovery cohort (cumulative incidence 0.18 versus 0.12, P = 0.002). This association was replicated in the validation cohort (0.16 versus 0.12, P = 0.02). It was still significant in multivariate models, adjusted for HIV transmission mode, viral load, CD4 T cells slope, age, antiretroviral therapy, tobacco smoking, hepatitis C virus coinfection, year of cohort entry and PJP prophylaxis (global subhazard ratio 1.42, 95% confidence interval 1.17-1.73, P = 0.0004).
CONCLUSION
Our data suggest rs2243250, a single nucleotide polymorphism known to influence IL-4 production, is associated with susceptibility to PJP in HIV-positive patients.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Medical Virology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Infectious Diseases
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > Immunology and Allergy
Life Sciences > Immunology
Health Sciences > Infectious Diseases
Language:English
Date:1 September 2019
Deposited On:31 Oct 2019 08:45
Last Modified:01 Oct 2020 15:36
Publisher:Lippincott Williams & Wilkins
ISSN:0269-9370
OA Status:Hybrid
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1097/QAD.0000000000002283
PubMed ID:31225812

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