Circulating Beta (1-3) Glucan and Immunoglobulin G Subclass Antibodies to Candida Albicans Cell Wall Antigens in Patients with Systemic Candidiasis

Invasive candidiasis in patients who are immunocompromised or in intensive care units (ICUs) presents both diagnostic and therapeutic problems. We previously described antibodies that were directed against Candida albicans cell wall fragments (CW), periodate-treated CW (CW(IO4)), phosphopeptidomannan (PPM), and beta(1-3) glucan. In this study, circulating fungal antigens [mannan and beta(1-3) glucan] and immunoglobulin G (IgG) subclass antibodies to these cell wall antigens (anti-CW) were analyzed in patients with systemic candidiasis. Sera were collected from 14 patients on two or three consecutive occasions, starting on the day when candidiasis was culture proven. The sera were analyzed by enzyme-linked immunosorbent assay. The control groups consisted of lactating mothers (n = 9) (group I) who had breast milk that was positive for C. albicans and also had acute inflammation of the nipples, and age-matched blood donors (n = 10) (group II). Within the first 3 weeks of Candida infection all of the patients were positive for beta(1-3) glucan by the Gluspecy test, but no patients were positive for mannan in the less-sensitive Pastorex Candida test. The controls were negative for both beta(1-3) glucan (<20 pg/ml) and mannan (<2.5 ng/ml). IgG1 anti-CW and IgG2 anti-PPM antibodies were the most discriminatory antibodies. The ratio of IgG1 anti-CW to IgG2 anti-PPM was significantly lower in nonsurviving patients than in the other patients within the first week of candidiasis (P = 0.019). The IgG2 levels of anti-CW(IO4) and antiglucan antibodies correlated strongly (r = 0.681; P < 0.0001), and the absence of these antibodies was associated with increased levels of beta(1-3) glucan. Increased levels of IgG1 anti-CW or IgG2 anti-PPM antibodies (titer of > or = 3 logs) or of a combination of the two antibodies (log sum, > or = 5) showed 92% sensitivity, 100% specificity, and positive predictive values. In conclusion, beta(1-3) glucan and the two subclass antibodies appear to be early specific markers for the laboratory diagnosis of candidiasis. Furthermore, the kinetics of beta(1-3) glucan appearance in serum may assist in evaluating the therapeutic efficacy of antifungal treatments.