PMID- 15629900
OWN - NLM
STAT- MEDLINE
DCOM- 20050614
LR  - 20071115
IS  - 0953-8178 (Print)
IS  - 0953-8178 (Linking)
VI  - 17
IP  - 2
DP  - 2005 Feb
TI  - Over-expressed IgG2 antibodies against O-acetylated sialoglycoconjugates 
      incapable of proper effector functioning in childhood acute lymphoblastic 
      leukemia.
PG  - 177-91
AB  - Earlier studies have demonstrated an over-expression of 9-O-acetylated 
      sialoglycoconjugates (9-OAcSGs) on lymphoblasts, concomitant with high titers of 
      anti-9-OAcSGs in childhood acute lymphoblastic leukemia (ALL). The present study 
      was aimed to evaluate whether this high induction of anti-9-OAcSGs at disease 
      presentation contributes toward immune surveillance. Accordingly, anti-9-OAcSGs 
      were affinity purified from sera of ALL patients and normal individuals, and 
      their specificity toward the glycotope having terminal 9-O-acetylated sialic 
      acid-linked subterminal N-acetyl galactosamine (GalNAc) in alpha2-6 manner 
      (9-OAcSAalpha2-6GalNAc) was established by hemagglutination assay, flow cytometry 
      and confocal microscopy. Subclass distribution of anti-9-OAcSGs revealed a 
      predominance of IgG2 in ALL. Analysis of glycosylation of anti-9-OAcSGs purified 
      from sera of ALL patients (IgG(ALL)) and normal individuals (IgG(N)) by 
      digoxigenin glycan enzyme assay, fluorimetric estimation, gas-liquid 
      chromatography and lectin-binding assays demonstrated that disease-specific 
      antibodies differ in content and nature as compared with normal controls. 
      Enhanced amount of 9-OAcSA-specific IgG2 induced in ALL was unable to trigger 
      activation of FcgammaR, the complement cascade and cell-mediated cytotoxicity, 
      although its glycotope-binding ability remains unaffected. Interestingly, only 
      IgG1N emerged as the potent mediator of cell-mediated cytotoxicity, complement 
      fixation and activator of effector cells through FcgammaR. In ALL, the observed 
      subclass switching of anti-9-OAcSGs to IgG2, alteration in their glycosylation 
      profile along with impairment of a few Fc-glycosylation-sensitive effector 
      functions hints toward a disbalanced homeostasis, thereby evading the host 
      defense. These findings justify further evaluation of the mechanism for 
      functional unresponsiveness of antibodies and production of 9-OAcSA-specific 
      chimeric antibodies with normal Fc domain for therapeutic applications.
FAU - Bandyopadhyay, Suman
AU  - Bandyopadhyay S
AD  - Immunobiology Division, Indian Institute of Chemical Biology, 4 Raja S.C. Mullick 
      Road, Jadavpur, Kolkata 700 032, India.
FAU - Bhattacharyya, Arindam
AU  - Bhattacharyya A
FAU - Mallick, Asish
AU  - Mallick A
FAU - Sen, Asish Kumar
AU  - Sen AK
FAU - Tripathi, Gayatri
AU  - Tripathi G
FAU - Das, Tanya
AU  - Das T
FAU - Sa, Gaurisankar
AU  - Sa G
FAU - Bhattacharya, Dilip Kumar
AU  - Bhattacharya DK
FAU - Mandal, Chitra
AU  - Mandal C
LA  - eng
PT  - Journal Article
DEP - 20050103
PL  - England
TA  - Int Immunol
JT  - International immunology
JID - 8916182
RN  - 0 (Glycoconjugates)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Receptors, Fc)
RN  - 0 (Sialic Acids)
SB  - IM
MH  - Child
MH  - Cytotoxicity, Immunologic/immunology
MH  - Glycoconjugates/chemistry/*immunology
MH  - Glycosylation
MH  - Humans
MH  - Immunoglobulin G/*blood/*immunology/isolation & purification
MH  - Precursor Cell Lymphoblastic Leukemia-Lymphoma/*immunology
MH  - Receptors, Fc/immunology
MH  - Sialic Acids/chemistry/*immunology
EDAT- 2005/01/05 09:00
MHDA- 2005/06/15 09:00
CRDT- 2005/01/05 09:00
PHST- 2005/01/05 09:00 [pubmed]
PHST- 2005/06/15 09:00 [medline]
PHST- 2005/01/05 09:00 [entrez]
AID - dxh198 [pii]
AID - 10.1093/intimm/dxh198 [doi]
PST - ppublish
SO  - Int Immunol. 2005 Feb;17(2):177-91. doi: 10.1093/intimm/dxh198. Epub 2005 Jan 3.