Abstract

Background: MBL is a natural human plasma protein that plays an important role in the humoral innate immune defense. MBL specifically recognizes a broad range of microorganisms, including bacteria, fungi, viruses, and parasites, by binding to common carbohydrate structures located on their surfaces and activating the lectin pathway of complement. The concentration of MBL in plasma is largely genetically determined and ranges from 5 to 10,000 ng/mL. Deficiency is caused by mutations within the mbl2 gene or its promoter region. Individuals heterozygous (A/O) and homozygous (O/O) for these mutations display a reduced level of MBL in plasma. Low levels of MBL have been associated with increased risk of serious infection in situations in which other components of the immune system are compromised. Studies in patients with hematologic malignancies undergoing chemotherapy suggest that low MBL levels or variant MBL genotypes (A/O or O/O) are correlated with infectious complications of chemotherapy and/or duration of febrile neutropenia. The effect of ethnicity on MBL level and genotype was examined as part of the development of recombinant human MBL (rhMBL), a novel molecule that is entering clinical trials.

Methods: The plasma MBL level (protein concentration) and MBL genotype of 80 healthy volunteers were determined by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (PCR), respectively.

Results: No differences in MBL level or genotype were observed among the 3 ethnic groups (see table below). Overall, the plasma MBL level was <100 ng/mL for 10% of the volunteers and <300 ng/mL for 16%. Regarding MBL genotype, 4% had an O/O genotype and 34% had an A/O genotype.

Conclusions: The MBL level and genotype data from 80 healthy volunteers of different ethnic backgrounds were observed to be generally concordant. Further analyses in individuals with other ethnicities are ongoing.

MBL Level and MBL Genotype by Ethnicity

WhiteBlackHispanicTotal
(N=50)(N=15)(N=15)(N=80)
n (%)n (%)n (%)n (%)
MBL Level (ng/mL)     
<100 5 (10) 1 (7) 2 (13) 8 (10) 
100 to <300 3 (6) 2 (13) 5 (6) 
≥300 42 (84) 12 (80) 13 (87) 67 (84) 
MBL Genotype     
A/A 32 (64) 9 (60) 9 (60) 50 (63) 
A/O 16 (34) 6 (40) 5 (33) 27 (34) 
O/O 2 (4) 1 (7) 3 (4) 
WhiteBlackHispanicTotal
(N=50)(N=15)(N=15)(N=80)
n (%)n (%)n (%)n (%)
MBL Level (ng/mL)     
<100 5 (10) 1 (7) 2 (13) 8 (10) 
100 to <300 3 (6) 2 (13) 5 (6) 
≥300 42 (84) 12 (80) 13 (87) 67 (84) 
MBL Genotype     
A/A 32 (64) 9 (60) 9 (60) 50 (63) 
A/O 16 (34) 6 (40) 5 (33) 27 (34) 
O/O 2 (4) 1 (7) 3 (4) 

Disclosures: Enzon Pharmaceuticals employees; IBT employees.; Stocks in Enzon.

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