title: Mannose-binding lectin contributes to the severity of Guillain-Barré syndrome.
abstract: In Guillain-Barré syndrome (GBS), complement activation plays a crucial role in the induction and extent of the postinfectious immune-mediated peripheral nerve damage. Mannose-binding lectin (MBL) activates the complement system via the lectin pathway after recognition of repetitive sugar groups on pathogens. We investigated whether the MBL2 genotype, serum MBL level, and MBL complex activity are associated with the development and severity of GBS. Single nucleotide polymorphisms in the promoter region (-550 H/L and -221 X/Y) and exon 1 (A/O) of the MBL2 gene were determined in 271 GBS patients and 212 healthy controls. The frequencies of the H allele, HY promoter haplotype, and HYA haplotype, which are related to high MBL activity, were all increased in GBS patients compared with healthy controls (p < or = 0.03), particularly in severely affected GBS patients (MRC-sum score < 40) (p < or = 0.02). Severe weakness was also associated with high MBL concentrations and MBL complex activity in sera from GBS patients (p < 0.01). The MBL2 B allele was associated with functional deficiency and relatively mild weakness. These results support the hypothesis that complement activation mediated by MBL contributes to the extent of nerve damage in GBS, which is codetermined by the MBL2 haplotype.
authors.affiliation: Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Karin
authors.initials: K
authors.lastname: Geleijns
authors.forename: Anja
authors.initials: A
authors.lastname: Roos
authors.forename: Jeanine J
authors.initials: JJ
authors.lastname: Houwing-Duistermaat
authors.forename: Wouter
authors.initials: W
authors.lastname: van Rijs
authors.forename: Anne P
authors.initials: AP
authors.lastname: Tio-Gillen
authors.forename: Jon D
authors.initials: JD
authors.lastname: Laman
authors.forename: Pieter A
authors.initials: PA
authors.lastname: van Doorn
authors.forename: Bart C
authors.initials: BC
authors.lastname: Jacobs
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002648:Child; D003167:Complement Activation / Q000276:immunology; D005260:Female; D005787:Gene Frequency; D020275:Guillain-Barre Syndrome / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*; D006239:Haplotypes; D006801:Humans; D008297:Male; D037601:Mannose-Binding Lectin / Q000096:biosynthesis / Q000097:blood / Q000235:genetics / Q000502:physiology*; D008875:Middle Aged; D012720:Severity of Illness Index
chemical_list: C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin