Antibody responses in HIV-infected patients with advanced immunosuppression and asymptomatic cryptococcal antigenemia

Admire Hlupeni, Antonio Nakouzi, Tao Wang, Kathryn F. Boyd, Tariro A. Makadzange, Chiratidzo E. Ndhlovu, Liise-anne Pirofski

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background There are no host biomarkers of risk for HIV-associated cryptococcal meningitis (CM) except CD4+ T-cell deficiency. At present, serum cryptococcal antigen (CrAg) screening of those with CD4 <100 cells/μL is used to identify persons at risk for HIV-associated CM. We determined if plasma antibody profiles could discriminate CrAg+ from CrAg-patients. Methods We performed serological analyses of 237 HIV-infected asymptomatic Zimbabwean patients with CD4 <100 cells/μL; 125 CrAg- A nd CrAg+ but cerebrospinal fluid CrAg-by CrAg lateral flow assay. We measured plasma immunoglobulin M (IgM), immunoglobulin G (IgG) 1, and IgG2 concentrations by Luminex, and titers of Cryptococcus neoformans (Cn) glucuronoxylomannan (GXM) polysaccharide and naturally occurring Laminarin (natural Lam, a β-(1-3)-glucan linked polysaccharide)-binding IgM and IgG by enzyme-linked immunosorbent assay. Results GXM-IgG,-IgM, and-IgG2 levels were significantly higher in CrAg+ patients, whereas natural Lam-IgM and Lam-IgG were higher in CrAg-patients before and after adjustment for age, sex, and CD4 T-cell count, despite overlap of values. To address this variability and better discriminate the groups, we used Akaike Information Criteria to select variables that independently predicted CrAg+ status and included them in a receiver operating characteristic curve to predict CrAg status. By inclusion of CD4, GXM-IgG, GXM-IgM, and Lam-IgG,-IgG2, and-IgM, this model had an 80.4% probability (95% confidence interval, 0.75-0.86) of predicting CrAg+ status. Conclusions Statistical models that include multiple serological variables may improve the identification of patients at risk for CM and inform new directions in research on the complex role that antibodies may play in resistance and susceptibility to CM.

Original languageEnglish (US)
JournalOpen Forum Infectious Diseases
Volume6
Issue number1
DOIs
StatePublished - Jan 1 2019

Fingerprint

Immunosuppression
Antibody Formation
HIV
Antigens
Immunoglobulin G
Cryptococcal Meningitis
Immunoglobulin M
Polysaccharides
T-Lymphocytes
Cryptococcus neoformans
Glucans
Antibodies
Statistical Models
CD4 Lymphocyte Count
ROC Curve
Cerebrospinal Fluid
Biomarkers
Enzyme-Linked Immunosorbent Assay
Confidence Intervals
glucuronoxylomannan

Keywords

  • antibody
  • cryptococccal antigenenmia
  • glucuronoxylomannan
  • HIV
  • IgG
  • IgM
  • immunoglobulin
  • Laminarin
  • Sub-Saharan Africa
  • Zimbabwe

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology

Cite this

Antibody responses in HIV-infected patients with advanced immunosuppression and asymptomatic cryptococcal antigenemia. / Hlupeni, Admire; Nakouzi, Antonio; Wang, Tao; Boyd, Kathryn F.; Makadzange, Tariro A.; Ndhlovu, Chiratidzo E.; Pirofski, Liise-anne.

In: Open Forum Infectious Diseases, Vol. 6, No. 1, 01.01.2019.

Research output: Contribution to journalArticle

Hlupeni, Admire ; Nakouzi, Antonio ; Wang, Tao ; Boyd, Kathryn F. ; Makadzange, Tariro A. ; Ndhlovu, Chiratidzo E. ; Pirofski, Liise-anne. / Antibody responses in HIV-infected patients with advanced immunosuppression and asymptomatic cryptococcal antigenemia. In: Open Forum Infectious Diseases. 2019 ; Vol. 6, No. 1.
@article{0d4c10c65dbf4011b3d5ab33db193441,
title = "Antibody responses in HIV-infected patients with advanced immunosuppression and asymptomatic cryptococcal antigenemia",
abstract = "Background There are no host biomarkers of risk for HIV-associated cryptococcal meningitis (CM) except CD4+ T-cell deficiency. At present, serum cryptococcal antigen (CrAg) screening of those with CD4 <100 cells/μL is used to identify persons at risk for HIV-associated CM. We determined if plasma antibody profiles could discriminate CrAg+ from CrAg-patients. Methods We performed serological analyses of 237 HIV-infected asymptomatic Zimbabwean patients with CD4 <100 cells/μL; 125 CrAg- A nd CrAg+ but cerebrospinal fluid CrAg-by CrAg lateral flow assay. We measured plasma immunoglobulin M (IgM), immunoglobulin G (IgG) 1, and IgG2 concentrations by Luminex, and titers of Cryptococcus neoformans (Cn) glucuronoxylomannan (GXM) polysaccharide and naturally occurring Laminarin (natural Lam, a β-(1-3)-glucan linked polysaccharide)-binding IgM and IgG by enzyme-linked immunosorbent assay. Results GXM-IgG,-IgM, and-IgG2 levels were significantly higher in CrAg+ patients, whereas natural Lam-IgM and Lam-IgG were higher in CrAg-patients before and after adjustment for age, sex, and CD4 T-cell count, despite overlap of values. To address this variability and better discriminate the groups, we used Akaike Information Criteria to select variables that independently predicted CrAg+ status and included them in a receiver operating characteristic curve to predict CrAg status. By inclusion of CD4, GXM-IgG, GXM-IgM, and Lam-IgG,-IgG2, and-IgM, this model had an 80.4{\%} probability (95{\%} confidence interval, 0.75-0.86) of predicting CrAg+ status. Conclusions Statistical models that include multiple serological variables may improve the identification of patients at risk for CM and inform new directions in research on the complex role that antibodies may play in resistance and susceptibility to CM.",
keywords = "antibody, cryptococccal antigenenmia, glucuronoxylomannan, HIV, IgG, IgM, immunoglobulin, Laminarin, Sub-Saharan Africa, Zimbabwe",
author = "Admire Hlupeni and Antonio Nakouzi and Tao Wang and Boyd, {Kathryn F.} and Makadzange, {Tariro A.} and Ndhlovu, {Chiratidzo E.} and Liise-anne Pirofski",
year = "2019",
month = "1",
day = "1",
doi = "10.1093/ofid/ofy333",
language = "English (US)",
volume = "6",
journal = "Open Forum Infectious Diseases",
issn = "2328-8957",
publisher = "Oxford University Press",
number = "1",

}

TY - JOUR

T1 - Antibody responses in HIV-infected patients with advanced immunosuppression and asymptomatic cryptococcal antigenemia

AU - Hlupeni, Admire

AU - Nakouzi, Antonio

AU - Wang, Tao

AU - Boyd, Kathryn F.

AU - Makadzange, Tariro A.

AU - Ndhlovu, Chiratidzo E.

AU - Pirofski, Liise-anne

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background There are no host biomarkers of risk for HIV-associated cryptococcal meningitis (CM) except CD4+ T-cell deficiency. At present, serum cryptococcal antigen (CrAg) screening of those with CD4 <100 cells/μL is used to identify persons at risk for HIV-associated CM. We determined if plasma antibody profiles could discriminate CrAg+ from CrAg-patients. Methods We performed serological analyses of 237 HIV-infected asymptomatic Zimbabwean patients with CD4 <100 cells/μL; 125 CrAg- A nd CrAg+ but cerebrospinal fluid CrAg-by CrAg lateral flow assay. We measured plasma immunoglobulin M (IgM), immunoglobulin G (IgG) 1, and IgG2 concentrations by Luminex, and titers of Cryptococcus neoformans (Cn) glucuronoxylomannan (GXM) polysaccharide and naturally occurring Laminarin (natural Lam, a β-(1-3)-glucan linked polysaccharide)-binding IgM and IgG by enzyme-linked immunosorbent assay. Results GXM-IgG,-IgM, and-IgG2 levels were significantly higher in CrAg+ patients, whereas natural Lam-IgM and Lam-IgG were higher in CrAg-patients before and after adjustment for age, sex, and CD4 T-cell count, despite overlap of values. To address this variability and better discriminate the groups, we used Akaike Information Criteria to select variables that independently predicted CrAg+ status and included them in a receiver operating characteristic curve to predict CrAg status. By inclusion of CD4, GXM-IgG, GXM-IgM, and Lam-IgG,-IgG2, and-IgM, this model had an 80.4% probability (95% confidence interval, 0.75-0.86) of predicting CrAg+ status. Conclusions Statistical models that include multiple serological variables may improve the identification of patients at risk for CM and inform new directions in research on the complex role that antibodies may play in resistance and susceptibility to CM.

AB - Background There are no host biomarkers of risk for HIV-associated cryptococcal meningitis (CM) except CD4+ T-cell deficiency. At present, serum cryptococcal antigen (CrAg) screening of those with CD4 <100 cells/μL is used to identify persons at risk for HIV-associated CM. We determined if plasma antibody profiles could discriminate CrAg+ from CrAg-patients. Methods We performed serological analyses of 237 HIV-infected asymptomatic Zimbabwean patients with CD4 <100 cells/μL; 125 CrAg- A nd CrAg+ but cerebrospinal fluid CrAg-by CrAg lateral flow assay. We measured plasma immunoglobulin M (IgM), immunoglobulin G (IgG) 1, and IgG2 concentrations by Luminex, and titers of Cryptococcus neoformans (Cn) glucuronoxylomannan (GXM) polysaccharide and naturally occurring Laminarin (natural Lam, a β-(1-3)-glucan linked polysaccharide)-binding IgM and IgG by enzyme-linked immunosorbent assay. Results GXM-IgG,-IgM, and-IgG2 levels were significantly higher in CrAg+ patients, whereas natural Lam-IgM and Lam-IgG were higher in CrAg-patients before and after adjustment for age, sex, and CD4 T-cell count, despite overlap of values. To address this variability and better discriminate the groups, we used Akaike Information Criteria to select variables that independently predicted CrAg+ status and included them in a receiver operating characteristic curve to predict CrAg status. By inclusion of CD4, GXM-IgG, GXM-IgM, and Lam-IgG,-IgG2, and-IgM, this model had an 80.4% probability (95% confidence interval, 0.75-0.86) of predicting CrAg+ status. Conclusions Statistical models that include multiple serological variables may improve the identification of patients at risk for CM and inform new directions in research on the complex role that antibodies may play in resistance and susceptibility to CM.

KW - antibody

KW - cryptococccal antigenenmia

KW - glucuronoxylomannan

KW - HIV

KW - IgG

KW - IgM

KW - immunoglobulin

KW - Laminarin

KW - Sub-Saharan Africa

KW - Zimbabwe

UR - http://www.scopus.com/inward/record.url?scp=85062396152&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85062396152&partnerID=8YFLogxK

U2 - 10.1093/ofid/ofy333

DO - 10.1093/ofid/ofy333

M3 - Article

VL - 6

JO - Open Forum Infectious Diseases

JF - Open Forum Infectious Diseases

SN - 2328-8957

IS - 1

ER -