BACKGROUND & AIMS: Nonimmune mechanisms of mucosal defense seem to be biologically important and might explain the observed variability in the course of enteric infection in immunodeficiency. Mannose-binding lectin (MBL) deficiency is associated with persistent diarrhea in children. We found that genetic determinants of MBL deficiency appear to predispose to cryptosporidiosis in patients with the acquired immunodeficiency syndrome (AIDS), and went on to study interactions of MBL and complement on Cryptosporidium parvum sporozoites. METHODS: This study involved cross-sectional study of MBL genotype and enteric infection in 72 Zambian AIDS patients with diarrhea, immunofluorescence analysis of MBL and C4 binding to C. parvum, and immunoblotting for MBL and complement in small intestinal fluid. RESULTS: Individuals homozygous for MBL structural gene mutations were at increased risk of cryptosporidiosis (odds ratio, 8.2; 95% confidence interval, 1. 5-42; P = 0.02). Lectin-mediated and concentration-dependent binding of purified MBL was detected on sporozoites but not oocysts, and MBL activated C4 on sporozoites. MBL, C3, C4, and albumin were detected in small intestinal fluid in half the patients tested, suggesting transudation of serum components into the enteropathic gut. CONCLUSIONS: The increased risk of cryptosporidiosis in MBL deficiency appears to include patients with AIDS. It may operate through MBL-mediated complement activation on sporozoites.
BACKGROUND & AIMS: Nonimmune mechanisms of mucosal defense seem to be biologically important and might explain the observed variability in the course of enteric infection in immunodeficiency. Mannose-binding lectin (MBL) deficiency is associated with persistent diarrhea in children. We found that genetic determinants of MBL deficiency appear to predispose to cryptosporidiosis in patients with the acquired immunodeficiency syndrome (AIDS), and went on to study interactions of MBL and complement on Cryptosporidium parvum sporozoites. METHODS: This study involved cross-sectional study of MBL genotype and enteric infection in 72 Zambian AIDSpatients with diarrhea, immunofluorescence analysis of MBL and C4 binding to C. parvum, and immunoblotting for MBL and complement in small intestinal fluid. RESULTS: Individuals homozygous for MBL structural gene mutations were at increased risk of cryptosporidiosis (odds ratio, 8.2; 95% confidence interval, 1. 5-42; P = 0.02). Lectin-mediated and concentration-dependent binding of purified MBL was detected on sporozoites but not oocysts, and MBL activated C4 on sporozoites. MBL, C3, C4, and albumin were detected in small intestinal fluid in half the patients tested, suggesting transudation of serum components into the enteropathic gut. CONCLUSIONS: The increased risk of cryptosporidiosis in MBL deficiency appears to include patients with AIDS. It may operate through MBL-mediated complement activation on sporozoites.
Authors: William Checkley; A Clinton White; Devan Jaganath; Michael J Arrowood; Rachel M Chalmers; Xian-Ming Chen; Ronald Fayer; Jeffrey K Griffiths; Richard L Guerrant; Lizbeth Hedstrom; Christopher D Huston; Karen L Kotloff; Gagandeep Kang; Jan R Mead; Mark Miller; William A Petri; Jeffrey W Priest; David S Roos; Boris Striepen; R C Andrew Thompson; Honorine D Ward; Wesley A Van Voorhis; Lihua Xiao; Guan Zhu; Eric R Houpt Journal: Lancet Infect Dis Date: 2014-09-29 Impact factor: 25.071