Circulating β (1-3) Glucan and Immunoglobulin G Subclass Antibodies toCandida albicansCell Wall Antigens in Patients with Systemic Candidiasis

Abstract

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 ␤(1-3) glucan. In this study, circulating fungal antigens [mannan and ␤(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 ␤(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 ␤(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 ␤(1-3) glucan. Increased levels of IgG1 anti-CW or IgG2 anti-PPM antibodies (titer of >3 logs) or of a combination of the two antibodies (log sum, >5) showed 92% sensitivity, 100% specificity, and positive predictive values. In conclusion, ␤(1-3) glucan and the two subclass antibodies appear to be early specific markers for the laboratory diagnosis of candidiasis. Furthermore, the kinetics of ␤(1-3) glucan appearance in serum may assist in evaluating the therapeutic efficacy of antifungal treatments.

Diagnostic Accuracy of Serum 1,3-β- d -Glucan for Pneumocystis jiroveci Pneumonia, Invasive Candidiasis, and Invasive Aspergillosis: Systematic Review and Meta-Analysis

“…The 36 studies included six assays: 17 used Fungitell (1,3,4,12,16,17,27,29,34,(45)(46)(47)(48)(49)(50)(51), 9 used the Fungitec G test (2,20,26,33,43,44,57,59,60), 6 used the Wako ␤-glucan test (14,19,24,40,54,56), 3 used the GKT-25 M set (32,61,62), and 1 used the fungal index (38). All studies but one were based in 1 of 13 countries, with the majority of assays in Japan (n ϭ 13), as well as in the United States (n ϭ 7), China (n ϭ 4), Spain (n ϭ 2), Austria (n ϭ 1), Belgium (n ϭ 1), Czech Republic (n ϭ 1), France (n ϭ 1), Germany (n ϭ 1), Kuwait (n ϭ 1), The Netherlands (n ϭ 1), Sweden (n ϭ 1), and Switzerland (n ϭ 1); one study that performed assays in multiple countries (Spain, Argentina, and France) was also included.…”

Antibodies against Glucan, Chitin, and Saccharomyces cerevisiae Mannan as New Biomarkers of Candida albicans Infection That Complement Tests Based on C. albicans Mannan

“…The sharp drop in anticarbohydrate antibody response observed around the time of blood culture suggests that the balance between mannanemia and antimannan antibodies observed previously in ICI patients (42) could also apply to glucanemia and antiglucan antibodies. Taking into account the fluctuations in ALCA response revealed in this study and fluctuations in glucanemia reported elsewhere (18), it would be worthwhile to investigate whether combined detection of serum glucans and ALCA could improve the sensitivity of diagnosis. Unfortunately, it was not possible to address the question of glucanemia in the present study because we could not guarantee the sterility of all serum samples.…”

Antibody-Mediated Protection through Cross-Reactivity Introduces a Fungal Heresy into Immunological Dogma

“…In support of this concept, in addition to protective MAbs, nonprotective MAbs to C. albicans, C. neoformans, and H. capsulatum have been described (13,25,28). Nonetheless, much remains to be learned about the nature of protective antibodies and the relationship between the natural antibody response and resistance and susceptibility to fungal pathogens, since hypogammaglobulinemia is not generally associated with the development of fungal disease and antibody responses to certain fungi and fungal targets can be a marker of disease rather than immunity (19,30).…”