Inherited mannose-binding lectin deficiency as evidenced by genetic and immunologic analyses: association with severe recurrent infections.
BACKGROUND
Mannose-binding lectin (MBL), an acute-phase serum protein of hepatic origin, plays an essential protective role in host innate immunity in targeting microbial pathogens for destruction via opsonization, enhancement of phagocytosis and complement activation. MBL deficiency, characterized by low serum MBL, has been attributed to genetic mutations in both structural and promoter regions of the gene coding for the protein. Concomitant MBL deficiency in patients with chronic immunologic disease has been associated with increased susceptibility to complicating infections that may hasten disease progression.


OBJECTIVE
Few cases of inherited MBL deficiency in adults and possible associations with recurrent infection have been reported. To address this issue, we investigated the MBL profile of four generations within a single adult family whose members have experienced a variety of persistent infections.


METHODS
MBL serum levels and MBL genotypes of each participating family member were ascertained by enzyme-linked immunoadsorbent assay and reverse transcriptase-polymerase chain reaction, respectively. MBL complement activation, as measured by C4b deposition against mannan-coated wells, was assayed using an enzyme-linked immunoadsorbent assay. Routine immunologic and cellular tests were carried out to evaluate the immunologic status of each family member.


RESULTS
Six of the 7 family members screened carried one or more of the variant MBL alleles in their genotype and had correspondingly low serum MBL and reduced ability to affect C4b opsonization. Medical histories of the participating family members revealed an array of mild to severe recurrent infections despite no apparent immunodeficiency.


CONCLUSIONS
Our studies show that MBL deficiency is an inherited characteristic and may be a crucial factor in maintaining immunologic health.
All Childrens Hospital/University of South Florida College of Medicine, Department of Pediatrics, Division of Allergy and Immunology, St. Petersburg, Florida 33701, USA.
Patricia
P
Martin
Aaron
A
Lerner
Lisa
L
Johnson
Danica L
DL
Lerner
Soichi
S
Haraguchi
Robert A
RA
Good
Noorbibi K
NK
Day
D000328:Adult; D004797:Enzyme-Linked Immunosorbent Assay; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007239:Infections / Q000235:genetics* / Q000276:immunology*; D008297:Male; D037601:Mannose-Binding Lectin / Q000097:blood* / Q000172:deficiency* / Q000235:genetics; D010375:Pedigree; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction
D037601:Mannose-Binding Lectin