Mannose binding lectin genotype as a risk factor for intestinal protozoal infection in AIDS

Abstract

Background Mannose binding lectin (MBL) is a multi-chain serum lectin with up to six 96 kDa subunits which plays an important role in non-specific defence against invasive organisms expressing polysaccharides terminating in mannose or N-acetyl glucosamine residues. Deficiencies of MBL predominantly arise from mutations in exon 1 of the MBL gene, at codons 52, 54 or 57. MBL gene mutations are over-represented in H1V positive populations, and are associated with shortened survival in AIDS. We examined MBL gene mutations in Zambian patients with AIDS related diarrhoea in order to determine whether they are associated with enhanced risk of enteric protozoal infections which might confer shortened survival. Methods 73 HIV seropositive patients with diarrhoea of over three weeks duration underwent stool microscopy, duodenal biopsy for evaluation of infection, and serum sampling. DNA was extracted from one frozen biopsy and used as the template for PCR amplification of exon 1; mutations were detected by controlled annealing of the products with a universal heteroduplex generator followed by polacrylamide electrophoresis. MBL concentrations in serum were assayed by ELISA. Results C. parvum was detected in 27%, L belli in 29%, and microsporidia in 32%. 46 of these patients had wild type MBL gene sequences, 20 were heterozygotes for the 57 codon mutation and 6 were homozygotes. MBL concentrations in serum were 1137 ~tg/l in wild types, 326 in heterozygotes, and 108 in homozygotes (p=0.0001). Individuals with MBL homozygous 57 codon mutations or 57/52 double mutations were at higher risk of cryptosporidiosis (Risk Ratio 3.1; 05%CI 1.6,6.0; p=0.006) but not of the other infections. Genotype predicted cryptosporidiosis, but serum MBL concentration did not. Conclusion In these AIDS patients, MBL mutations conferred higher risk for cryptosporidiosis than the wild type. No extra risk of other protozoal infection was observed. This extra risk for cryptosporidiosis could partially explain the shortened survival in AIDS experienced by individuals with MBL gene mutations.