IL-4 polymorphism influences susceptibility to Pneumocystis jirovecii pneumonia in HIV-positive patients. AIDS
Wojtowicz et al. aimed to describe the role of polymorphisms from 21 candidate genes encoding relevant fungal pattern recognition receptors (PRRs) and cytokines/chemokines with regards to the predisposition to Pneumocystis jirovecii pneumonia (PJP) in the patients from the Swiss HIV Cohort Study (SHCS). The analysis included patients with a nadir CD4+ T-cell count less than 200 cells/µl, divided into a discovery (N=1’645) and a replication (N=1’861) cohort.
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).
In conclusion, this data demonstrates an association between PJP and the presence of the interleukin-4-590T/C polymorphism in a large cohort of HIV patients. This single nucleodide polymorphisms may influence the Th2/Th1 responses required for appropriate immunity against Pneumocystis spp. and increase susceptibility to infection in HIV-positive patients with low level of CD4+ T cells