Cryptococcal meningitis is a cause for cross-reactivity in cerebrospinal fluid assays for anti-Histoplasma, anti-Coccidioides and anti-Blastomyces antibodies

Nathan C. Bahr, Anil A. Panackal, Michelle M. Durkin, Melinda L. Smedema, Wesley Keown, Thomas Davis, Luke Raymond-Guillen, Yoon Dong Park, Kieren A. Marr, Bettina C. Fries, Peter R. Williamson, David R. Boulware, L. Joseph Wheat

Research output: Contribution to journalArticle

Abstract

Background/Objectives: Antibody detection is commonly used for diagnosis of histoplasmosis, and cross-reactions have been recognised due to endemic mycoses but not cryptococcosis. We observed cross-reactions in an anti-Histoplasma antibody enzyme immunoassay (EIA) in the cerebrospinal fluid (CSF) from a patient with cryptococcal meningitis and sought to assess the risk of cross-reactive anti-Histoplasma antibodies in persons with cryptococcal meningitis. Methods: An anti-cryptococcal antibody EIA was developed to measure CSF antibody response in HIV-infected subjects from Kampala, Uganda and previously healthy, HIV-negative subjects at the National Institutes of Health (NIH) with cryptococcal meningitis. Specimens were tested for cross-reactivity in assays for IgG anti-Histoplasma, anti-Blastomyces and anti-Coccidioides antibodies. Results: Among 61 subjects with cryptococcal meningitis (44 Kampala cohort, 17 NIH cohort), elevated CSF anti-cryptococcal antibody levels existed in 38% (23/61). Of the 23 CSF specimens containing elevated anti-cryptococcal antibodies, falsely positive results were detected in antibody EIAs for histoplasmosis (8/23, 35%), coccidioidomycosis (6/23, 26%) and blastomycosis (1/23, 4%). Overall, 2% (2/81) of control CSF specimens had elevated anti-cryptococcal antibody detected, both from Indiana. Conclusions: Cryptococcal meningitis may cause false-positive results in the CSF for antibodies against Histoplasma, Blastomyces and Coccidioides. Fungal antigen testing should be performed to aid in differentiating true- and false-positive antibody results in the CSF.

Original languageEnglish (US)
JournalMycoses
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Blastomyces
Coccidioides
Cryptococcal Meningitis
Histoplasma
Cerebrospinal Fluid
Anti-Idiotypic Antibodies
Histoplasmosis
Antibodies
Cross Reactions
National Institutes of Health (U.S.)
Immunoenzyme Techniques
Fungal Antigens
HIV
Blastomycosis
Coccidioidomycosis
Cryptococcosis
Uganda
Mycoses
Antibody Formation

Keywords

  • antibody detection
  • Blastomycosis
  • coccidioidomycosis
  • cross-reactivity
  • Cryptococcosis
  • Histoplasmosis

ASJC Scopus subject areas

  • Dermatology
  • Infectious Diseases

Cite this

Cryptococcal meningitis is a cause for cross-reactivity in cerebrospinal fluid assays for anti-Histoplasma, anti-Coccidioides and anti-Blastomyces antibodies. / Bahr, Nathan C.; Panackal, Anil A.; Durkin, Michelle M.; Smedema, Melinda L.; Keown, Wesley; Davis, Thomas; Raymond-Guillen, Luke; Park, Yoon Dong; Marr, Kieren A.; Fries, Bettina C.; Williamson, Peter R.; Boulware, David R.; Wheat, L. Joseph.

In: Mycoses, 01.01.2019.

Research output: Contribution to journalArticle

Bahr, NC, Panackal, AA, Durkin, MM, Smedema, ML, Keown, W, Davis, T, Raymond-Guillen, L, Park, YD, Marr, KA, Fries, BC, Williamson, PR, Boulware, DR & Wheat, LJ 2019, 'Cryptococcal meningitis is a cause for cross-reactivity in cerebrospinal fluid assays for anti-Histoplasma, anti-Coccidioides and anti-Blastomyces antibodies', Mycoses. https://doi.org/10.1111/myc.12882
Bahr, Nathan C. ; Panackal, Anil A. ; Durkin, Michelle M. ; Smedema, Melinda L. ; Keown, Wesley ; Davis, Thomas ; Raymond-Guillen, Luke ; Park, Yoon Dong ; Marr, Kieren A. ; Fries, Bettina C. ; Williamson, Peter R. ; Boulware, David R. ; Wheat, L. Joseph. / Cryptococcal meningitis is a cause for cross-reactivity in cerebrospinal fluid assays for anti-Histoplasma, anti-Coccidioides and anti-Blastomyces antibodies. In: Mycoses. 2019.
@article{fe483978ab9446e1844ead2b0ae0a1b5,
title = "Cryptococcal meningitis is a cause for cross-reactivity in cerebrospinal fluid assays for anti-Histoplasma, anti-Coccidioides and anti-Blastomyces antibodies",
abstract = "Background/Objectives: Antibody detection is commonly used for diagnosis of histoplasmosis, and cross-reactions have been recognised due to endemic mycoses but not cryptococcosis. We observed cross-reactions in an anti-Histoplasma antibody enzyme immunoassay (EIA) in the cerebrospinal fluid (CSF) from a patient with cryptococcal meningitis and sought to assess the risk of cross-reactive anti-Histoplasma antibodies in persons with cryptococcal meningitis. Methods: An anti-cryptococcal antibody EIA was developed to measure CSF antibody response in HIV-infected subjects from Kampala, Uganda and previously healthy, HIV-negative subjects at the National Institutes of Health (NIH) with cryptococcal meningitis. Specimens were tested for cross-reactivity in assays for IgG anti-Histoplasma, anti-Blastomyces and anti-Coccidioides antibodies. Results: Among 61 subjects with cryptococcal meningitis (44 Kampala cohort, 17 NIH cohort), elevated CSF anti-cryptococcal antibody levels existed in 38{\%} (23/61). Of the 23 CSF specimens containing elevated anti-cryptococcal antibodies, falsely positive results were detected in antibody EIAs for histoplasmosis (8/23, 35{\%}), coccidioidomycosis (6/23, 26{\%}) and blastomycosis (1/23, 4{\%}). Overall, 2{\%} (2/81) of control CSF specimens had elevated anti-cryptococcal antibody detected, both from Indiana. Conclusions: Cryptococcal meningitis may cause false-positive results in the CSF for antibodies against Histoplasma, Blastomyces and Coccidioides. Fungal antigen testing should be performed to aid in differentiating true- and false-positive antibody results in the CSF.",
keywords = "antibody detection, Blastomycosis, coccidioidomycosis, cross-reactivity, Cryptococcosis, Histoplasmosis",
author = "Bahr, {Nathan C.} and Panackal, {Anil A.} and Durkin, {Michelle M.} and Smedema, {Melinda L.} and Wesley Keown and Thomas Davis and Luke Raymond-Guillen and Park, {Yoon Dong} and Marr, {Kieren A.} and Fries, {Bettina C.} and Williamson, {Peter R.} and Boulware, {David R.} and Wheat, {L. Joseph}",
year = "2019",
month = "1",
day = "1",
doi = "10.1111/myc.12882",
language = "English (US)",
journal = "Mycoses",
issn = "0933-7407",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - Cryptococcal meningitis is a cause for cross-reactivity in cerebrospinal fluid assays for anti-Histoplasma, anti-Coccidioides and anti-Blastomyces antibodies

AU - Bahr, Nathan C.

AU - Panackal, Anil A.

AU - Durkin, Michelle M.

AU - Smedema, Melinda L.

AU - Keown, Wesley

AU - Davis, Thomas

AU - Raymond-Guillen, Luke

AU - Park, Yoon Dong

AU - Marr, Kieren A.

AU - Fries, Bettina C.

AU - Williamson, Peter R.

AU - Boulware, David R.

AU - Wheat, L. Joseph

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background/Objectives: Antibody detection is commonly used for diagnosis of histoplasmosis, and cross-reactions have been recognised due to endemic mycoses but not cryptococcosis. We observed cross-reactions in an anti-Histoplasma antibody enzyme immunoassay (EIA) in the cerebrospinal fluid (CSF) from a patient with cryptococcal meningitis and sought to assess the risk of cross-reactive anti-Histoplasma antibodies in persons with cryptococcal meningitis. Methods: An anti-cryptococcal antibody EIA was developed to measure CSF antibody response in HIV-infected subjects from Kampala, Uganda and previously healthy, HIV-negative subjects at the National Institutes of Health (NIH) with cryptococcal meningitis. Specimens were tested for cross-reactivity in assays for IgG anti-Histoplasma, anti-Blastomyces and anti-Coccidioides antibodies. Results: Among 61 subjects with cryptococcal meningitis (44 Kampala cohort, 17 NIH cohort), elevated CSF anti-cryptococcal antibody levels existed in 38% (23/61). Of the 23 CSF specimens containing elevated anti-cryptococcal antibodies, falsely positive results were detected in antibody EIAs for histoplasmosis (8/23, 35%), coccidioidomycosis (6/23, 26%) and blastomycosis (1/23, 4%). Overall, 2% (2/81) of control CSF specimens had elevated anti-cryptococcal antibody detected, both from Indiana. Conclusions: Cryptococcal meningitis may cause false-positive results in the CSF for antibodies against Histoplasma, Blastomyces and Coccidioides. Fungal antigen testing should be performed to aid in differentiating true- and false-positive antibody results in the CSF.

AB - Background/Objectives: Antibody detection is commonly used for diagnosis of histoplasmosis, and cross-reactions have been recognised due to endemic mycoses but not cryptococcosis. We observed cross-reactions in an anti-Histoplasma antibody enzyme immunoassay (EIA) in the cerebrospinal fluid (CSF) from a patient with cryptococcal meningitis and sought to assess the risk of cross-reactive anti-Histoplasma antibodies in persons with cryptococcal meningitis. Methods: An anti-cryptococcal antibody EIA was developed to measure CSF antibody response in HIV-infected subjects from Kampala, Uganda and previously healthy, HIV-negative subjects at the National Institutes of Health (NIH) with cryptococcal meningitis. Specimens were tested for cross-reactivity in assays for IgG anti-Histoplasma, anti-Blastomyces and anti-Coccidioides antibodies. Results: Among 61 subjects with cryptococcal meningitis (44 Kampala cohort, 17 NIH cohort), elevated CSF anti-cryptococcal antibody levels existed in 38% (23/61). Of the 23 CSF specimens containing elevated anti-cryptococcal antibodies, falsely positive results were detected in antibody EIAs for histoplasmosis (8/23, 35%), coccidioidomycosis (6/23, 26%) and blastomycosis (1/23, 4%). Overall, 2% (2/81) of control CSF specimens had elevated anti-cryptococcal antibody detected, both from Indiana. Conclusions: Cryptococcal meningitis may cause false-positive results in the CSF for antibodies against Histoplasma, Blastomyces and Coccidioides. Fungal antigen testing should be performed to aid in differentiating true- and false-positive antibody results in the CSF.

KW - antibody detection

KW - Blastomycosis

KW - coccidioidomycosis

KW - cross-reactivity

KW - Cryptococcosis

KW - Histoplasmosis

UR - http://www.scopus.com/inward/record.url?scp=85059333044&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85059333044&partnerID=8YFLogxK

U2 - 10.1111/myc.12882

DO - 10.1111/myc.12882

M3 - Article

C2 - 30565753

AN - SCOPUS:85059333044

JO - Mycoses

JF - Mycoses

SN - 0933-7407

ER -