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

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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
JournalThe Journal of infectious diseases
Volume219
Issue number3
DOIs
StatePublished - Jan 9 2019

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Immune Reconstitution Inflammatory Syndrome
Cryptococcus
Antibody Formation
Immunoglobulin M
Immunoglobulin G
HIV
B-Lymphocytes
Cryptococcal Meningitis
Antibodies
CD4 Lymphocyte Count
laminaran
Viral Load
Capsules
Cerebrospinal Fluid
Immunoglobulins
Immunity
Multivariate Analysis
Biomarkers

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Cite this

Association Between Plasma Antibody Responses and Risk for Cryptococcus-Associated Immune Reconstitution Inflammatory Syndrome. / Yoon, Hyun Ah; Nakouzi, Antonio; Chang, Christina C.; Kuniholm, Mark H.; Carreño, Leandro J.; Wang, Tao; Ndung'u, Thumbi; Lewin, Sharon R.; French, Martyn A.; Pirofski, Liise-anne.

In: The Journal of infectious diseases, Vol. 219, No. 3, 09.01.2019, p. 420-428.

Research output: Contribution to journalArticle

Yoon, Hyun Ah ; Nakouzi, Antonio ; Chang, Christina C. ; Kuniholm, Mark H. ; Carreño, Leandro J. ; Wang, Tao ; Ndung'u, Thumbi ; Lewin, Sharon R. ; French, Martyn A. ; Pirofski, Liise-anne. / Association Between Plasma Antibody Responses and Risk for Cryptococcus-Associated Immune Reconstitution Inflammatory Syndrome. In: The Journal of infectious diseases. 2019 ; Vol. 219, No. 3. pp. 420-428.
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T1 - Association Between Plasma Antibody Responses and Risk for Cryptococcus-Associated Immune Reconstitution Inflammatory Syndrome

AU - Yoon, Hyun Ah

AU - Nakouzi, Antonio

AU - Chang, Christina C.

AU - Kuniholm, Mark H.

AU - Carreño, Leandro J.

AU - Wang, Tao

AU - Ndung'u, Thumbi

AU - Lewin, Sharon R.

AU - French, Martyn A.

AU - Pirofski, Liise-anne

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N2 - 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.

AB - 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.

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