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 H.
AU - Carreño, Leandro J.
AU - Wang, Tao
AU - Ndung'u, Thumbi
AU - Lewin, Sharon R.
AU - French, Martyn A.
AU - Pirofski, Liise Anne
N1 - Publisher Copyright:
© 2018 The Author(s).
PY - 2019/1/9
Y1 - 2019/1/9
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.
KW - Cryptococcus-associated immune reconstitution inflammatory syndrome
KW - GXM
KW - HIV
KW - IgG
KW - IgM
KW - cryptococcal meningitis
KW - laminarin
KW - memory B cells
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U2 - 10.1093/infdis/jiy447
DO - 10.1093/infdis/jiy447
M3 - Article
C2 - 30010905
AN - SCOPUS:85059797704
SN - 0022-1899
VL - 219
SP - 420
EP - 428
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 3
ER -