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Prepublished online as a Blood First Edition Paper on July 5, 2002; DOI 10.1182/blood-2002-06-1627.
Submitted June 5, 2002
Accepted June 25, 2002
Increased frequency of mannose-binding lectin insufficiency among children with acute lymphoblastic leukemia
Kjeld Schmiegelow*, Peter Garred, Birgitte Lausen, Bente Andreassen, Bodil Laub Petersen, and Hans Ole Madsen
Pediatric Clinic II, H S Rigshospitalet, Copenhagen, Denmark
Department of Clinical Immunology, H S Rigshospitalet, Copenhagen, Denmark
Department of Pathology, H S Rigshospitalet, Copenhagen, Denmark
* Corresponding author; email: kschmiegelow{at}rh.dk.
Background: Epidemiological data indicate that acute lymphoblastic leukemia (ALL) could be induced by interactions between the immune system and early childhood infections. Mannose-binding lectin (MBL) plays a critical role in the immune response in early childhood before specific immune protection develops. We investigated whether there may be an association between childhood ALL and low producing MBL genotypes. Serum MBL levels depend on normal (A) or defective (O) alleles, and on normal (Y) or reduced (X) promotor activities. Patients and methods: 137 non-infants with ALL and 250 controls were classified into 3 MBL genotype groups according to their influence on the serum level of functional MBL: I) YA/YA and YA/XA (higher levels), II) XA/XA and YA/O (intermediate levels), and III) MBL insufficiency with XA/O or O/O (MBL-deficient) genotypes. Results: Compared to controls, cases more often had low-level genotypes (I/II/III: 63 (46%)/44 (32%)/30 (22%) vs 145 (58%)/65 (26%)/40 (16%), p=0.02) and MBL-deficiency (8.8% vs 2.8%; p=0.009). Thus, the ALL odds ratio for MBL-deficient vs non-deficient individuals was 3.3 (95% CI: 1.3-8.7), whereas the ALL odds ratio for group I vs group II/III genotypes was 0.62 (95% CI: 0.41-0.94). MBL group III patients were significantly younger at diagnosis than those in group I/II (Median: 3.9 vs 5.2 years, p=0.04). Interpretation: The study shows that the presence of low-level MBL genotypes is associated with an increased risk of childhood ALL particularly with early age at onset.
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