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IL-4 polymorphism influences susceptibility to Pneumocystis jirovecii pneumonia 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/?l, 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.

SUBMITTER: Wojtowicz A

PROVIDER: S-EPMC6686957 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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

Wójtowicz Agnieszka A Bibert Stéphanie S Taffé Patrick P Bernasconi Enos E Furrer Hansjakob H Günthard Huldrych F HF Hoffmann Matthias M Osthoff Michael M Cavassini Matthias M Bochud Pierre-Yves PY

AIDS (London, England) 20190901 11

<h4>Objectives</h4>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.<h4>Design and methods</h4>The analysis included patients with a nadir CD4 T-cell count less than 200 cells/μl, div ...[more]

PMID: 31225812

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Project description:ObjectiveThe current study evaluated the diagnostic performance of serum (1,3)-beta-D Glucan (BDG) in differentiating PJP from P. jirovecii-colonization in HIV-uninfected patients with P. jirovecii PCR-positive results.MethodsThis was a single-center retrospective study between 2019 and 2021. The diagnosis of PJP was based on the following criteria: detection of P. jirovecii in sputum or BAL specimen by qPCR or microscopy; Meet at least two of the three criteria: (1) have respiratory symptoms of cough and/or dyspnea, hypoxia; (2) typical radiological picture findings; (3) receiving a complete PJP treatment. After exclusion, the participants were divided into derivation and validation cohorts. The derivation cohort defined the cut-off value of serum BDG. Then, it was verified using the validation cohort.ResultsTwo hundred and thirteen HIV-uninfected patients were enrolled, with 159 PJP and 54 P. jirovecii-colonized patients. BDG had outstanding specificity, LR, and PPV for PJP in both the derivation (90.00%, 8.900, and 96.43%) and the validation (91.67%, 9.176, and 96.30%) cohorts at ≥ 117.7 pg/mL. However, it had lower sensitivity and NPV in the derivation cohort (89.01% and 72.97%), which was even lower in the validation cohort (76.47% and 57.89%). Of note, BDG ≥ 117.7 pg/mL has insufficient diagnostic efficacy for PJP in patients with lung cancer, interstitial lung disease (ILD) and nephrotic syndrome. And although lymphocytes, B cells, and CD4+ T cells in PJP patients were significantly lower than those in P. jirovecii-colonized patients, the number and proportion of peripheral blood lymphocytes did not affect the diagnostic efficacy of serum BDG.ConclusionsSerum BDG ≥ 117.7 pg/mL could effectively distinguish P. jirovecii-colonization from infection in qPCR-positive HIV-uninfected patients with infectious diseases, solid tumors (excluding lung cancer), autoimmune or inflammatory disorders, and hematological malignancies. Of note, for patients with lung cancer, ILD, and nephrotic diseases, PJP should be cautiously excluded at BDG < 117.7 pg/mL.

Dataset Information

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

Publications

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

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