Chronic Disseminated Candidiasis During Hematological Malignancies: An Immune Reconstitution Inflammatory Syndrome With Expansion of Pathogen-Specific T Helper Type 1 Cells

Background. Chronic disseminated candidiasis (CDC) is a rare disease that mostly occurs after chemotherapy-induced prolonged neutropenia in patients with hematological malignancies. It is believed to ensue from Candida colonization, breach of the intestinal epithelial barrier, and venous translocation to organs. Fungal blood or liver biopsy cultures are generally negative, suggesting the absence of an ongoing invasive fungal disease. Methods. To unravel the contribution of the immune system to CDC pathogenesis, we undertook a prospective multicentric exploratory study in 44 CDC patients at diagnosis and 44 matched controls. Results. Analysis of Candida-specific T-cell responses using enzyme-linked immunospot assays revealed higher numbers of interferon (IFN)gamma-producing T cells reactive to mp65 or candidin in 27 CDC cases compared with 33 controls. Increased plasma levels of soluble CD25, interleukin (IL)-6, IL-1 beta, tumor necrosis factor-alpha, and IL-10 and lower levels of IL-2 were observed in CDC patients versus controls. Neutrophilia and higher levels of CD4 and CD8 T-cell activation were found in CDC patients as well as increased proportions of CXCR3-expressing TCR gamma delta V+delta 2(+) cells. Conclusions. The expansion of Candida-specific IFN gamma-producing T cells together with features of T-cell activation and systemic inflammation identified here support the view that CDC belongs to the broad spectrum of fungal-associated immune reconstitution inflammatory syndromes.