Abstract
Paracoccidioidomycosis (PCM) is an important endemic, systemic disease in Latin America caused by Paracoccidioides spp. This mycosis has been associated with high morbidity and sequels, and its clinical manifestations depend on the virulence of the infecting strain, the degree and type of immune response, infected tissues, and intrinsic characteristics of the host. The T helper(Th)1 and Th17/Th22 cells are related to resistance and control of infection, and a Th2/Th9 response is associated with disease susceptibility. In this study, we focused on interleukin(IL)-12p35 (IL12A), IL-18 (IL18), and IFN-γ receptor 1 (IFNGR1) genetic polymorphisms because their respective roles have been described in human PCM. Real-time PCR was employed to analyze IL12A-504 G/T (rs2243115), IL18-607 C/A (rs1946518), and IFNGR1-611 A/G (rs1327474) single nucleotide polymorphisms (SNP). One hundred forty-nine patients with the acute form (AF), multifocal chronic (MC), or unifocal chronic (UC) forms of PCM and 110 non-PCM individuals as a control group were included. In the unconditional logistic regression analysis adjusted by ethnicity and sex, we observed a high risk of the IL18-607 A-allele for both AF [p = 0.015; OR = 3.10 (95% CI: 1.24–7.77)] and MC groups [p = 0.023; OR = 2.61 (95% CI: 1.14–5.96)] when compared with UC. The IL18-607 A-allele associated risk for the AF and MC groups as well as the protective role of the C-allele in UC are possibly linked to higher levels of IL-18 at different periods of the course of the disease. Therefore, a novel role of IL18-607 C/A SNP is shown in the present study, highlighting its importance in the outcome of PCM.
Highlights
Paracoccidioidomycosis (PCM) is one of the main endemic, systemic mycoses in Latin America, and it is caused by the thermally dimorphic fungi of the Paracoccidioides brasiliensis (P. brasiliensis) complex (Paracoccidioides spp.) and Paracoccidioides lutzii
Thirty-nine patients had the acute form of PCM (AF) and 110 had the chronic form (CF); 93 had the multifocal chronic form (MC) and 17 had the unifocal chronic (UC) form
Eight single nucleotide polymorphisms (SNP) or mutations on DC-SIGN, human leukocyte antigen (HLA), IL-4, IL-10, IL-12Rβ1, and Vitamin D receptor genes were found to have an association with risk, outcome, or clinical forms of PCM
Summary
Paracoccidioidomycosis (PCM) is one of the main endemic, systemic mycoses in Latin America, and it is caused by the thermally dimorphic fungi of the Paracoccidioides brasiliensis (P. brasiliensis) complex (Paracoccidioides spp.) and Paracoccidioides lutzii. PCM is associated with high morbidity and sequels; because it is not a compulsorily notified disease in Brazil, the actual data are based on reports of epidemiological surveys, case series, hospitalization, and mortality data [1]. It is endemic in the southeast, central west, and south regions of Brazil and estimated at 0.71–2.70/100,000 inhabitants/year [2]. The clinical manifestations depend on the virulence of the infecting strain, the degree and type of immune response, infected tissues, and intrinsic characteristics of the host [4]
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