Over-expressed IgG2 antibodies against O-acetylated sialoglycoconjugates incapable of proper effector functioning in childhood acute lymphoblastic leukemia
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| Title |
Over-expressed IgG2 antibodies against O-acetylated sialoglycoconjugates incapable of proper effector functioning in childhood acute lymphoblastic leukemia
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| Creator |
Bandyopadhyay, Suman
Bhattacharyya, Arindam Mallick, Asish Sen, Asish Kumar Tripathi, Gayatri Das, Tanya Sa, Gaurisankar Bhattacharya, Dilip Kumar Mandal, Chitra |
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| Subject |
Infectious Diseases and Immunology
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| Description |
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 a2–6 manner (9-OAcSAa2–6GalNAc) 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 (IgGALL) and normal individuals (IgGN) 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 FccR, 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 FccR. 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
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| Date |
2005
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/572/1/INTERNATIONAL_IMMUNOLOGY_17(_2)_177%2D191;2005[100].pdf
Bandyopadhyay, Suman and Bhattacharyya, Arindam and Mallick, Asish and Sen, Asish Kumar and Tripathi, Gayatri and Das, Tanya and Sa, Gaurisankar and Bhattacharya, Dilip Kumar and Mandal, Chitra (2005) Over-expressed IgG2 antibodies against O-acetylated sialoglycoconjugates incapable of proper effector functioning in childhood acute lymphoblastic leukemia. International Immunology, 17 (2). pp. 177-191. |
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| Relation |
http://dx.doi.org/10.1093/intimm/dxh198
http://www.eprints.iicb.res.in/572/ |
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