Abstract:
: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.
journal_name
Int Immunoljournal_title
International immunologyauthors
Bandyopadhyay S,Bhattacharyya A,Mallick A,Sen AK,Tripathi G,Das T,Sa G,Bhattacharya DK,Mandal Cdoi
10.1093/intimm/dxh198subject
Has Abstractpub_date
2005-02-01 00:00:00pages
177-91issue
2eissn
0953-8178issn
1460-2377pii
dxh198journal_volume
17pub_type
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