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 ≤ 0.03), particularly in severely affected GBS patients (MRC-sum score <40) (p ≤ 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.

Genotypes Coding for Low Serum Levels of Mannose-Binding Lectin Are Underrepresented among Individuals Suffering from Noninfectious Systemic Inflammatory Response Syndrome

“…In the present study nonsignificant differences for the frequencies of MBL2 haplotypes and genotypes were observed between ICU patients with SIRS and healthy controls. The prevalence of low-MBL2 genotypes was similar to the frequency observed by Garcia-Laorden et al in Spain (10) and others in previous studies (17,18). LYPB, as previously reported in other Caucasian populations (1,46), was the predominant variant type of haplotype both in the group of patients with SIRS and in the healthy blood donors.…”

Association between Mannose-Binding Lectin Deficiency and Septic Shock following Acute Pyelonephritis Due toEscherichia coli

“…Genetically defined MBL deficiency is remarkably common in the general population, with an estimated prevalence of more than 10 to 15% in several Caucasian populations (17,18). In our study, the MBL2 genotype frequencies observed in the healthy control group closely resembled those previously reported in a Canary Islands (Spain) population (9), which in turn was similar to that observed in other healthy control groups from several European studies performed with Caucasian populations (1,12,13). LYPB, as previously reported, was the predominant variant type haplotype both in the healthy control group and in the patients with AP.…”

“…The multivariate analysis has revealed that the presence of MBL2 genotypes associated with low MBL production was the only variable associated with septic shock even though other clinical variables, such as age, immunosuppression, and diabetes mellitus, previously related to AP with an unfavorable outcome (27,29,32,44) were also included in the study. Although one possible limitation of our study is the fact that serum MBL levels were not measured, the relationship between MBL2 genotypes and serum MBL levels has been clearly established in numerous studies (12,13,40). Therefore, MBL2 genotyping could be of clinical interest as a molecular marker defining patients with AP at risk for septic shock.…”

Mass Spectrometry in the Elucidation of the Glycoproteome of Bacterial Pathogens

“…More serious conditions that can arise from C. jejuni infections include Guillain-Barré syndrome, which is the most common cause of acute flaccid paralysis in the United States [171] and Miller-Fisher syndrome. These diseases result in damage to the nerve gangliosides by antibody mediated axonal cytoskeletal breakdown and peri-synaptic Schwann cell damage.…”

“…The link between these neuropathies and C. jejuni is thought to come about due to the bodies' production of antibodies against C. jejuni lipopolysaccharides (in C. jejuni these are analogous to lipooligosaccharides of mucosal pathogens), which cross-react with gangliosides. It is believed that lectin-binding proteins within the immune system recognize glycan binding sites on pathogens and activate the complement system thus producing these cross-reactive antibodies [171,172]. This crossreactivity is thought in part to be due to the presence of Nacetyl neuraminic acid (Neu5Ac) (9) that is displayed in prominent positions on vertebral cells and is critical for a number of physiological processes including neuronal plasticity [173], and is also found on the oligosaccharide portion of C. jejuni cell surface proteins.…”