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

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

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background
Initiation of antiretroviral therapy (ART) in 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, Cryptococcus neoformans (CN) glucuronoxylomannan (GXM) capsule-specific and (Lam)inarin-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=0.0003), Lam-IgM (P=0.0005), Lam-IgG (P=0.002), and GXM-IgM (P=0.002) 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
JournalJournal of Infectious Diseases
Volume219
Issue number3
DOIs
Publication statusPublished - 1 Feb 2019

Cite this

Yoon, Hyun Ah ; Nakouzi, Antonio ; Chang, Christina C. ; Kuniholm, Mark ; Carreño, Leandro J. ; Wang, Tao ; Ndung'u, Thumbi ; Lewin, Sharon Ruth ; French, Martyn A ; Pirofski, Liise-Anne. / Association between plasma antibody responses and risk for Cryptococcus-associated immune reconstitution inflammatory syndrome. In: Journal of Infectious Diseases. 2019 ; Vol. 219, No. 3. pp. 420-428.
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title = "Association between plasma antibody responses and risk for Cryptococcus-associated immune reconstitution inflammatory syndrome",
abstract = "BackgroundInitiation of antiretroviral therapy (ART) in 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.MethodsWe compared plasma levels of immunoglobulins, Cryptococcus neoformans (CN) glucuronoxylomannan (GXM) capsule-specific and (Lam)inarin-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.ResultsPrior 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=0.0003), Lam-IgM (P=0.0005), Lam-IgG (P=0.002), and GXM-IgM (P=0.002) 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.DiscussionAntibody 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.",
author = "Yoon, {Hyun Ah} and Antonio Nakouzi and Chang, {Christina C.} and Mark Kuniholm and Carre{\~n}o, {Leandro J.} and Tao Wang and Thumbi Ndung'u and Lewin, {Sharon Ruth} and French, {Martyn A} and Liise-Anne Pirofski",
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Association between plasma antibody responses and risk for Cryptococcus-associated immune reconstitution inflammatory syndrome. / Yoon, Hyun Ah; Nakouzi, Antonio ; Chang, Christina C.; Kuniholm, Mark; Carreño, Leandro J. ; Wang, Tao; Ndung'u, Thumbi; Lewin, Sharon Ruth; French, Martyn A; Pirofski, Liise-Anne.

In: Journal of Infectious Diseases, Vol. 219, No. 3, 01.02.2019, p. 420-428.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

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

AU - Carreño, Leandro J.

AU - Wang, Tao

AU - Ndung'u, Thumbi

AU - Lewin, Sharon Ruth

AU - French, Martyn A

AU - Pirofski, Liise-Anne

PY - 2019/2/1

Y1 - 2019/2/1

N2 - BackgroundInitiation of antiretroviral therapy (ART) in 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.MethodsWe compared plasma levels of immunoglobulins, Cryptococcus neoformans (CN) glucuronoxylomannan (GXM) capsule-specific and (Lam)inarin-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.ResultsPrior 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=0.0003), Lam-IgM (P=0.0005), Lam-IgG (P=0.002), and GXM-IgM (P=0.002) 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.DiscussionAntibody 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 - BackgroundInitiation of antiretroviral therapy (ART) in 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.MethodsWe compared plasma levels of immunoglobulins, Cryptococcus neoformans (CN) glucuronoxylomannan (GXM) capsule-specific and (Lam)inarin-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.ResultsPrior 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=0.0003), Lam-IgM (P=0.0005), Lam-IgG (P=0.002), and GXM-IgM (P=0.002) 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.DiscussionAntibody 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.

U2 - 10.1093/infdis/jiy447

DO - 10.1093/infdis/jiy447

M3 - Article

VL - 219

SP - 420

EP - 428

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

IS - 3

ER -