Heteroligomeric forms of codon 54 mannose binding lectin (MBL) in circulation demonstrate reduced in vitro function

Mannose binding lectin (MBL) is a pattern recognition molecule that plays a pivotal role in innate immunity. This liver derived, circulating plasma protein binds organisms displaying high-density carbohydrate structures and flags them for destruction via opsonisation and initiation of the lectin pathway of the complement cascade. The present study reveals native, oligomeric forms of human MBL in plasma from healthy blood donors of differing genotypes and correlates the relative abundance of observed molecular weight species with mannan binding activity and C4 deposition in vitro. Wild type (A/A) individuals demonstrate predominately high molecular weight MBL that correlated with high mannan binding capacity and C4 deposition. A/C individuals demonstrated predominantly low molecular weight MBL with decreased mannan binding and C4 deposition activity. A/D individuals demonstrated both high molecular weight and low molecular weight MBL with reduced mannan binding and C4 deposition predominantly seen in combination with LX promoter. We identified A/B individuals as a unique group with large variation in MBL level, mannan binding activity and C4 deposition and propose a model for C4 deposition based on differential binding of MASP.