Common polymorphisms in critical genes of innate immunity do not contribute to the risk for chronic disseminated candidiasis in adult leukemia patients

Abstract

Chronic disseminated candidiasis is a serious fungal infection in immunocompromised patients, particularly those undergoing therapy for acute leukemia. Coordination between innate and adaptive immune system is critical to resistance or susceptibility to Candida infection. In order to investigate possible genetic contribution to chronic disseminated candidiasis of key molecules in the innate immune pathway, we performed a case control study using the candidate gene approach. Forty subjects with chronic disseminated candidiasis and 50 controls without chronic disseminated candidiasis but an underlying diagnosis of leukemia were enrolled in the Helsinki University Central Hospital during the period 1980-1998. Candidate genes were selected for analysis based upon the following criteria: a common polymorphism (>5% frequency) and existence a priori of clinical and biological data suggesting a role for the variant in the pathogenesis of chronic disseminated candidiasis. Six genes were selected from critical microbicidal and innate immune pathways, including three low-affinity Fcgamma receptors (FCGR2A, FCGR3A and FCGR3B), chitotriosidase (CHIT1), p22-phox NADPH oxidase (CYBA), and mannose binding lectin (MBL2). There was no statistically significant association of susceptibility to chronic disseminated candidiasis with the polymorphisms in this study. Common variants in the six studied genes most likely do not contribute to the risk for chronic disseminated candidiasis in patients with acute leukemia.

Adjuvant Corticosteroid Therapy for Chronic Disseminated Candidiasis

“…Indeed, in one study, a common haplotype of the IL-4 promoter was overrepresented in patients with CDC [31]. However, a study by the same group challenged this result by showing that common polymorphisms in 6 critical genes of innate immunity did not contribute to an increased risk of CDC [32].…”

Human chitotriosidase polymorphism is associated with human longevity in Mediterranean nonagenarians and centenarians

“…This supports the existence of a 'healthy aging' phenotype in which individuals somehow delay or avoid major clinical disease and disability until late in life. Although previous studies have suggested that CHIT-1-deficient individuals show a certain degree of disadvantage, such as increased susceptibility to parasitic disease infections, to microorganisms containing chitin and to Gram-negative infections, 17,[31][32][33][34][35] other studies indicate that CHIT-1 deficiency is not a disadvantage but rather a selective advantage. [36][37] Given the very high gene frequency of the main mutant allele, as shown in this study, it seems more likely that in humans, selection has occurred in the direction of decreasing or eliminating the activity of this enzyme.…”

Association of lectin pathway proteins with intra-abdominal Candida infection in high-risk surgical intensive-care unit patients. A prospective cohort study within the fungal infection network of Switzerland

“…In our cohort candidemia was only detected in two patients, which might be related to early diagnosis and treatment or the more frequent use of pre-emptive antifungal treatment (18/89). Lastly, MBL2 variant alleles were similarly distributed in adult leukemia patients with and without chronic disseminated candidiasis in a third study (35).…”