Use of an artificial antigen containing the 3,6-di-O-methyl-β-D-glucopyranosyl epitope for the serodiagnosis of leprosy

Sangnae Cho, T. Fujiwara, S. W. Hunter, T. H. Rea, R. H. Gelber, P. J. Brennan

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

The coupling of synthetic 3,6-di-O-methyl-β-D-glucopyranosyl-(1→4)-2,3-di-O-methyl-α-L-rhamnopyra nose, the hapten determinant of phenolic glycolipid I from Mycobacterium leprae, to bovine serum albumin (BSA) by reductive amination produced the antigen ε-N-1-[1-deoxy-2,3-di-O-methyl-4-O-(3',6'-di-O-methyl-β-D-glucopyranosyl )-rhamnitol]-lysyl-BSA, which proved highly sensitive in ELISA and showed good concordance with the native glycolipid in analysis of serum samples from 223 leprosy patients. Conjugates prepared from 6-O-methyl-β-D-glucopyranosyl- or β-D-glucopyranosyl-containing disaccharides were inactive and those containing noncyclic 3,6-di-O-methyl-glucitol showed little activity. Thus 3,6-di-O-methyl-β-D-glucopyranose in its cyclic hemiacetal form is necessary for binding anti-glycolipid IgM from leprosy patients. Analysis of serum samples from healthy subjects showed a false-positive rate of 2.4% (four of 169) against the glycolipid and 3.6% (six of 169) against the glycoconjugate. Comparable figures for samples of sera of tuberculosis patients were 3.0% (two of 66) and 9.0% (six of 66), respectively. Alternative synthesizing strategies may diminish this cross-reactivity. The prospects of a fully synthetic specific antigen for the worldwide serodiagnosis of leprosy look promising.

Original languageEnglish
Pages (from-to)311-322
Number of pages12
JournalJournal of Infectious Diseases
Volume150
Issue number3
DOIs
Publication statusPublished - 1984 Jan 1

Fingerprint

Glycolipids
Serologic Tests
Leprosy
Epitopes
Bovine Serum Albumin
Antigens
Serum
Amination
Synthetic Vaccines
Glycoconjugates
Sorbitol
Haptens
Disaccharides
Nose
Healthy Volunteers
Tuberculosis
Enzyme-Linked Immunosorbent Assay

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Infectious Diseases

Cite this

Cho, Sangnae ; Fujiwara, T. ; Hunter, S. W. ; Rea, T. H. ; Gelber, R. H. ; Brennan, P. J. / Use of an artificial antigen containing the 3,6-di-O-methyl-β-D-glucopyranosyl epitope for the serodiagnosis of leprosy. In: Journal of Infectious Diseases. 1984 ; Vol. 150, No. 3. pp. 311-322.
@article{a89bd9529bdc446f8a01afa9fcb85a99,
title = "Use of an artificial antigen containing the 3,6-di-O-methyl-β-D-glucopyranosyl epitope for the serodiagnosis of leprosy",
abstract = "The coupling of synthetic 3,6-di-O-methyl-β-D-glucopyranosyl-(1→4)-2,3-di-O-methyl-α-L-rhamnopyra nose, the hapten determinant of phenolic glycolipid I from Mycobacterium leprae, to bovine serum albumin (BSA) by reductive amination produced the antigen ε-N-1-[1-deoxy-2,3-di-O-methyl-4-O-(3',6'-di-O-methyl-β-D-glucopyranosyl )-rhamnitol]-lysyl-BSA, which proved highly sensitive in ELISA and showed good concordance with the native glycolipid in analysis of serum samples from 223 leprosy patients. Conjugates prepared from 6-O-methyl-β-D-glucopyranosyl- or β-D-glucopyranosyl-containing disaccharides were inactive and those containing noncyclic 3,6-di-O-methyl-glucitol showed little activity. Thus 3,6-di-O-methyl-β-D-glucopyranose in its cyclic hemiacetal form is necessary for binding anti-glycolipid IgM from leprosy patients. Analysis of serum samples from healthy subjects showed a false-positive rate of 2.4{\%} (four of 169) against the glycolipid and 3.6{\%} (six of 169) against the glycoconjugate. Comparable figures for samples of sera of tuberculosis patients were 3.0{\%} (two of 66) and 9.0{\%} (six of 66), respectively. Alternative synthesizing strategies may diminish this cross-reactivity. The prospects of a fully synthetic specific antigen for the worldwide serodiagnosis of leprosy look promising.",
author = "Sangnae Cho and T. Fujiwara and Hunter, {S. W.} and Rea, {T. H.} and Gelber, {R. H.} and Brennan, {P. J.}",
year = "1984",
month = "1",
day = "1",
doi = "10.1093/infdis/150.3.311",
language = "English",
volume = "150",
pages = "311--322",
journal = "Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "Oxford University Press",
number = "3",

}

Use of an artificial antigen containing the 3,6-di-O-methyl-β-D-glucopyranosyl epitope for the serodiagnosis of leprosy. / Cho, Sangnae; Fujiwara, T.; Hunter, S. W.; Rea, T. H.; Gelber, R. H.; Brennan, P. J.

In: Journal of Infectious Diseases, Vol. 150, No. 3, 01.01.1984, p. 311-322.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Use of an artificial antigen containing the 3,6-di-O-methyl-β-D-glucopyranosyl epitope for the serodiagnosis of leprosy

AU - Cho, Sangnae

AU - Fujiwara, T.

AU - Hunter, S. W.

AU - Rea, T. H.

AU - Gelber, R. H.

AU - Brennan, P. J.

PY - 1984/1/1

Y1 - 1984/1/1

N2 - The coupling of synthetic 3,6-di-O-methyl-β-D-glucopyranosyl-(1→4)-2,3-di-O-methyl-α-L-rhamnopyra nose, the hapten determinant of phenolic glycolipid I from Mycobacterium leprae, to bovine serum albumin (BSA) by reductive amination produced the antigen ε-N-1-[1-deoxy-2,3-di-O-methyl-4-O-(3',6'-di-O-methyl-β-D-glucopyranosyl )-rhamnitol]-lysyl-BSA, which proved highly sensitive in ELISA and showed good concordance with the native glycolipid in analysis of serum samples from 223 leprosy patients. Conjugates prepared from 6-O-methyl-β-D-glucopyranosyl- or β-D-glucopyranosyl-containing disaccharides were inactive and those containing noncyclic 3,6-di-O-methyl-glucitol showed little activity. Thus 3,6-di-O-methyl-β-D-glucopyranose in its cyclic hemiacetal form is necessary for binding anti-glycolipid IgM from leprosy patients. Analysis of serum samples from healthy subjects showed a false-positive rate of 2.4% (four of 169) against the glycolipid and 3.6% (six of 169) against the glycoconjugate. Comparable figures for samples of sera of tuberculosis patients were 3.0% (two of 66) and 9.0% (six of 66), respectively. Alternative synthesizing strategies may diminish this cross-reactivity. The prospects of a fully synthetic specific antigen for the worldwide serodiagnosis of leprosy look promising.

AB - The coupling of synthetic 3,6-di-O-methyl-β-D-glucopyranosyl-(1→4)-2,3-di-O-methyl-α-L-rhamnopyra nose, the hapten determinant of phenolic glycolipid I from Mycobacterium leprae, to bovine serum albumin (BSA) by reductive amination produced the antigen ε-N-1-[1-deoxy-2,3-di-O-methyl-4-O-(3',6'-di-O-methyl-β-D-glucopyranosyl )-rhamnitol]-lysyl-BSA, which proved highly sensitive in ELISA and showed good concordance with the native glycolipid in analysis of serum samples from 223 leprosy patients. Conjugates prepared from 6-O-methyl-β-D-glucopyranosyl- or β-D-glucopyranosyl-containing disaccharides were inactive and those containing noncyclic 3,6-di-O-methyl-glucitol showed little activity. Thus 3,6-di-O-methyl-β-D-glucopyranose in its cyclic hemiacetal form is necessary for binding anti-glycolipid IgM from leprosy patients. Analysis of serum samples from healthy subjects showed a false-positive rate of 2.4% (four of 169) against the glycolipid and 3.6% (six of 169) against the glycoconjugate. Comparable figures for samples of sera of tuberculosis patients were 3.0% (two of 66) and 9.0% (six of 66), respectively. Alternative synthesizing strategies may diminish this cross-reactivity. The prospects of a fully synthetic specific antigen for the worldwide serodiagnosis of leprosy look promising.

UR - http://www.scopus.com/inward/record.url?scp=0021195610&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0021195610&partnerID=8YFLogxK

U2 - 10.1093/infdis/150.3.311

DO - 10.1093/infdis/150.3.311

M3 - Article

C2 - 6207246

AN - SCOPUS:0021195610

VL - 150

SP - 311

EP - 322

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

IS - 3

ER -