Increased levels of Candida albicans mannan-specific T-cell-derived antigen binding molecules in patients with invasive candidiasis

Abstract

In addition to cytokines, CD4+ T cells have been found to secrete soluble, T-cell-derived antigen binding molecules (TABMs). These antigen-specific immunoproteins are thought to have immunoregulatory properties in the suppression of cell-mediated immunity (CMI) because they often associate with interleukin-10 (IL-10) and transforming growth factor beta. Decreased CMI causes susceptibility to infections caused by organisms which are normally nonpathogenic. In this situation, e.g., Candida albicans saprophytism may develop into invasive candidiasis. The difficult diagnosis of invasive candidiasis is based on the findings obtained from blood cultures and with tissue biopsy specimens, with some additional diagnostic value gained by the detection of Candida albicans mannan antigenemia and antimannan antibodies. In the present study, Candida albicans mannan-specific TABM (CAM-TABM) levels in the sera of patients with invasive candidiasis (n = 11), Candida colonization (n = 11) and noncolonization (n = 10), recurrent vulvovaginal candidiasis (n = 30), and atopic eczema dermatitis syndrome (n = 59) and healthy controls (n = 30) were analyzed. For 14 participants, the effect of mannan stimulation on TABM production and gamma interferon (IFN-gamma) and IL-4 mRNA expression by peripheral blood lymphocytes was also studied. It was demonstrated that CAM-TABM production was the highest in patients with invasive candidiasis and that CAM-TABM levels could distinguish Candida-colonized patients from noncolonized patients. In addition, the CAM-TABM level was directly related to mRNA expression for IL-4 but not IFN-gamma. These results reinforce the view that TABMs are associated with decreased CMI, immunoregulation, and the T-helper cell 2-type immune response.

FIG. 1.

C. albicans mannan-specific (A) and IHR-specific (B) TABM levels of the study groups. INV, invasive candidiasis patients (n = 11); COL, Candida-colonized patients (n = 11); HOSP, hospitalized, noncolonized patients who had undergone gastrointestinal surgery (n = 10); RVVC, recurrent vulvovaginal candidiasis patients (n = 30); AEDS-1, atopic eczema dermatitis syndrome patients, group 1 (n = 59), HC-1, healthy controls, group 1 (n = 30). Significant differences (P < 0.05, Mann-Whitney U test) are shown. The bars represent medians. TABM levels are expressed as arbitrary ELISA units (see Materials and Methods).

FIG. 2.

Levels of antigen-specific TABM to C. albicans mannan and whole-cell extract (IHR) and Malassezia furfur (MF) determined in Candida-colonized (n = 42) and noncolonized (n = 68) patients. The significant difference of the means (P < 0.05, Student's t test) and the standard errors of the means are shown. TABM levels are expressed as arbitrary ELISA units (see Materials and Methods). NS, not significant.

FIG. 3.

Correlations (regression analysis) between the levels of antigen-specific TABM to C. albicans mannan (CAM) and whole-cell extract (IHR) and Malassezia furfur (MF) of serum samples of all study subjects (n = 151).

FIG. 4.

CAM-TABM levels and the changes (Δ) in IL-4 and IFN-γ mRNA expression in cultures of PBMCs from AEDS patients (solid lines; n = 8) and healthy controls (dotted lines; n = 6) after 7 days of incubation with (CAM) and without (RPMI) mannan.

FIG. 5.

IL-4 mRNA expression of high-level (n = 7) versus low-level (n = 7) TABM producers (TABM production indices, greater than or equal to and less than −0.78, respectively). The index is equal to CAM_TABM − RPMI_TABM. The P value was obtained by the Mann-Whitney U test. Medians and their absolute deviations are shown.