Identification of two anti- Candida antibodies associated with the survival of patients with candidemia

Abstract

ABSTRACT We retrospectively studied antibody immunity in 92 candidemia patients, using sera taken at candidemia diagnosis. All patients showed the presence of IgG antibodies against all tested Candida antigens, namely Als3, Mp65, Hyr1 and Eno1, at levels significantly higher than those of non-candidemia controls. Both correlation and multivariable logistic regression analyses showed that the antibodies against Als3 and-Mp65, two known immunodominant and virulence-related proteins, were significantly associated with lower 30-day patient mortality. In particular, high titers of anti-Als3 antibodies were associated with survival in all subgroups of frail, more critical patients (over-median aged, infected by C. albicans or with septic shock) while high anti-Mp65 IgG levels were associated with survival in younger patients and in those infected by non- albicans Candida species or showing no signs of septic shock. A multivariable logistic model including anti-Als3 or anti-MP65 antibody levels and other variables, such as the serum β-glucan level at candidemia diagnosis, septic shock occurrence, the presence of diabetes, and initial antifungal treatment with fluconazole, was highly predictive of candidemia outcome, with an area under the curve of 0.85–0.86. Overall, the data demonstrate the ability of candidemia patients to mount a sustained memory antibody response to Candida antigens and that some of these responses have a sizeable impact on patient survival. Our data invite consideration of a multicenter, prospective investigation of antibody immunity in candidemia. IMPORTANCE Candidemia (bloodstream invasion by Candida species) is a major fungal disease in humans. Despite the recent progress in diagnosis and treatment, therapeutic options are limited and under threat of antimicrobial resistance. The disease mortality remains high (around 40%). In contrast with deep-seated invasive candidiasis, particularly that occurring in patients with hematologic malignancies and organ transplants, patients with candidemia are often not immunocompromised and therefore able to mount memory anticandidal immune responses, perhaps primed by Candida commensalism. We investigated antibody immunity in candidemia patients and report here on the ability of these patients to produce antibodies that react with Candida antigens. In particular, the patients with high titers of IgG reactive with two immunodominant, virulence-associated antigens (Als3 and MP65) had a higher 30-day survival. If confirmed by controlled, prospective clinical studies, our data could inform the development of antibody therapy to better treat a severe fungal infection such as candidiasis.