Antibodies against 9-O-acetylated sialoglycans: a potent marker to monitor clinical status in childhood acute lymphoblastic leukemia.
BACKGROUND
Although childhood acute lymphoblastic leukemia (ALL) is highly responsive to chemotherapy, reliable techniques are needed to determine treatment outcome and predict impending relapse. In ALL, the cell surface over expression of 9-O-acetylated sialoglycans (9-OAcSGs) on lymphoblasts and concomitant high antibody titers in patients' sera was reported.


OBJECTIVE
The present study was aimed to evaluate whether anti-9-OAcSG titers can be harnessed to monitor the clinical outcome of ALL.


METHODS
Anti-9-OAcSGs were analyzed by ELISA in children receiving either UK ALL X (n = 69, Group I) in India or UK ALL 97 (n = 47, Group II) in UK along with age-matched normal healthy controls at different time points over a period of >2 years. An attempt was also made to investigate subclass distribution of disease-specific IgG. Moreover, 17 patients having a higher sample size were longitudinally monitored.


RESULTS
Antibody levels were raised at disease presentation, decreased with remission induction, and importantly, reappeared with clinical relapse. Sera from patients with other hematological disorders and normal controls showed negligible levels of circulating anti-9-OAcSGs. In patients of both Groups I and II, the assay showed high sensitivity (98.92% and 96.77%) and specificity (92.1% and 95.91%), respectively. IgG subclass analyses during different phases of treatment revealed that 9-OAcSG-specific IgG(1) could serve as a better prognostic marker in ALL.


CONCLUSIONS
This study demonstrated the potential of this disease-specific antibody as an alternate marker in diagnosis and long-term assessment of ALL patients, suggesting its application in detection and prediction of impending relapse. Therefore, the expression of anti-9-OAcSGs, irrespective of their treatment protocol, may serve as an economical yet effective index for monitoring of childhood ALL.
Pal
Santanu
S
Immunobiology Division, Indian Institute of Chemical Biology, Jadavpur-700 032, India.
Bandyopadhyay
Suman
S
Chatterjee
Mitali
M
Bhattacharya
Dilip K
DK
Minto
Lynne
L
Hall
Andrew G
AG
Mandal
Chitra
C
D000970:Antineoplastic Agents / Q000627:therapeutic use; D001323:Autoantibodies / Q000097:blood* / Q000302:isolation & purification; D014408:Biomarkers, Tumor / Q000097:blood* / Q000191:economics; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000191:economics; D007194:India / Q000453:epidemiology; D008297:Male; D011134:Polysaccharides / Q000097:blood / Q000737:chemistry / Q000276:immunology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D011379:Prognosis; D011446:Prospective Studies; D011947:Receptors, Antigen, B-Cell / Q000097:blood / Q000191:economics; D012680:Sensitivity and Specificity; D012794:Sialic Acids / Q000737:chemistry*; D006113:United Kingdom / Q000453:epidemiology
D000970:Antineoplastic Agents; D001323:Autoantibodies; D014408:Biomarkers, Tumor; D007074:Immunoglobulin G; D011134:Polysaccharides; D011947:Receptors, Antigen, B-Cell; D012794:Sialic Acids