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

Author:

Candon Sophie12,Rammaert Blandine345,Foray Anne Perrine1,Moreira Baptiste1,Gallego Hernanz Maria Pilar6,Chatenoud Lucienne1,Lortholary Olivier37

Affiliation:

1. Université Paris-Descartes, Faculté de Médecine, INSERM U1151-CNRS UMR 8253, Assistance Publique-Hôpitaux de Paris (APHP), Hôpital Necker-Enfants Malades, APHP, Immunologie Biologique, Paris, France

2. Université de Rouen Normandie, INSERM U1234, CHU de Rouen Normandie, Rouen, France

3. Université Paris Descartes, Faculté de Médecine, APHP, Hôpital Necker-Enfants Malades, Service de Maladies Infectieuses et Tropicales, Centre d’Infectiologie Necker-Pasteur, IHU Imagine, Paris, France

4. Université de Poitiers, Faculté de Médecine et Pharmacie, Poitiers, France

5. CHU de Poitiers, Service de Maladies Infectieuses et Tropicales, Poitiers, France

6. CHU de Poitiers, Service d’Hématologie, Poitiers, France

7. Institut Pasteur, Unité de Mycologie Moléculaire, Paris, France

Abstract

Abstract 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)γ-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-1β, tumor necrosis factor-α, 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 TCRγδ +Vδ2+ cells. Conclusions The expansion of Candida-specific IFNγ-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.

Funder

Programme Hospitalier de Recherche Clinique - PHRC 2012

Ministry of Health

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Immunology and Allergy

Reference52 articles.

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3. New insights into hepatosplenic Candidosis, a manifestation of chronic disseminated candidosis;Rammaert;Mycoses,2012

4. Usefulness of corticosteroid therapy during chronic disseminated Candidiasis: case reports and literature review;Chaussade;J Antimicrob Chemother,2012

5. Chronic disseminated Candidiasis complicated by immune reconstitution inflammatory syndrome in child with acute lymphoblastic leukemia;Zając-Spychała;Case Rep Hematol,2016

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