Association Between Plasma Antibody Responses and Risk for Cryptococcus-Associated Immune Reconstitution Inflammatory Syndrome

Hyun Ah Yoon, Antonio Nakouzi, Christina C. Chang, Mark H. Kuniholm, Leandro J. Carreño, Tao Wang, Thumbi Ndung'u, Sharon R. Lewin, Martyn A. French, Liise Anne Pirofski

Research output: Contribution to journalArticle

10 Scopus citations

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 (US)
Pages (from-to)420-428
Number of pages9
JournalJournal of Infectious Diseases
Volume219
Issue number3
DOIs
StatePublished - Jan 9 2019

Keywords

  • Cryptococcus-associated immune reconstitution inflammatory syndrome
  • GXM
  • HIV
  • IgG
  • IgM
  • cryptococcal meningitis
  • laminarin
  • memory B cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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