Association between plasma antibody responses and risk for Cryptococcus-associated immune reconstitution inflammatory syndrome

Hyun Ah Yoon, Antonio Nakouzi, Christina Chang, M Kuniholm , LJ Carreno, Tao Wang, Thumbi Ndung'u, Sharon Lewin, Martyn French, Liise-anne Pirofski

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

Background
Initiation of antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-infected individuals with cryptococcal meningitis places them at risk for Cryptococcus-associated immune reconstitution inflammatory syndrome (C-IRIS). The relationship between antibody immunity and C-IRIS risk has not been investigated.

Methods
We compared plasma levels of immunoglobulins, C. neoformans glucuronoxylomannan (GXM) capsule-specific and laminarin (Lam)-binding IgM and IgG, and percentages of peripheral blood total and memory B cells between 27 HIV-infected patients with CM who developed C-IRIS and 63 who did not, and evaluated associations of these parameters with risk of C-IRIS.

Results
Prior to initiation of ART, plasma IgM, Lam-binding IgM (Lam-IgM), Lam-IgG, and GXM-IgM levels were significantly lower in patients who developed C-IRIS than those who did not. Multivariate analysis revealed significant inverse associations between C-IRIS and IgM (P = .0003), Lam-IgM (P = .0005), Lam-IgG (P = .002), and GXM-IgM (P = .002) independent of age, sex, HIV viral load, CD4+ T-cell count, and cerebrospinal fluid fungal burden. There were no associations between C-IRIS and total or memory B cells.

Discussion
Antibody profiles that include plasma IgM, Lam-IgM, Lam-IgG, and/or GXM-IgM may have value in furthering our understanding of C-IRIS pathogenesis and hold promise as candidate biomarkers of C-IRIS risk.
Original languageEnglish
Pages (from-to)420-428
Number of pages9
JournalThe Journal of infectious diseases
Volume219
Issue number3
Early online date16 Jul 2018
DOIs
Publication statusPublished - 9 Jan 2019

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