Association Between CD1 Gene Polymorphisms And Susceptibility To Guillain-Barre Syndrome

Backgroud and ObjectiveGuillain-Barre syndrome (GBS) is an immune mediated polyneuropathy that is related with precedent infections. Molecular mimicry between glycolipid antigens expressed by an infective antigen such as Campylobacter jejuni and the human peripheral nerve has been hypothesized to be the causative mechanism of GBS. CD1 molecules are MHC-like glycoproteins that take part in antigen presentation and processing of glycolipids and lipids, which is now believed to be decisive in the development of GBS. There are five closely linked CD1 genes in humans located in chromosome 1 (named CD1A, B, C, D, and E) all showing limited polymorphism in exon 2, however only result in amino acid substitutions in CD1a and CD1e. There are researches show that the polymorphisms express in the normal people such as European,American, the hans people and national minorities of China,etc,reports about the relation between CD1 molecule and the neuroimmune diseases(Polymyositis, myasthenia gravis, Multiple Sclerosis,etc) also can be found.At present,there are few studys investigate the relation between GBS and gene polymorphisms,the Italian researcher Caporale investigated the GBS patients of Italy,found that between GBS patients and normal people,the variance of CD1 gene polymorphisms had significance,but another research from Dutch researcher Kuijf fonund the variance of CD1 gene polymorphisms had no significance between GBS patients of Northern European and the normal people.Report about the relation between GBS patients of Chinese and the CD1 gene polymorphisms has not been found in China.At present, the research about the relationship between CD1 gene polymorphisms and Susceptibility to Guillain-Barre syndrome is quite rare, so we aimed to find the association and to investigate the immunogenetical mechanism of GBS.Patients and methodsFifty-six consecutive GBS patients (35 males and 21 females, age:31.2±5.3years, range 11 to 55 years) were enrolled in the study from July in 2008 to Aug. in 2010 according to the diagnostic criteria and categories proposed by Asbury etc. Sixty-seven unrelated randomly selected healthy subjects without the history of precedent infection and autoimmune diseases constituted the control group for genetic studies(40 males and 27 females, age:32.3±6.7 years, range 10 to 57 years). All the subjects are drown venous blood 3ML and 2 ML and all the species were preserved at the temperature of -40℃relativly. The serum of blood 3ML are tested Campylobacter Jejuni (CJ) with ELISA. DNA was extracted according to the protocol of the manufacturer (Blood Genomic DNA Extraction Kit, BioMed, Germany) and kept at -40℃until use. DNA segments corresponding to exon 2 of CD 1 A, and CD1E genes were PCR amplified from genomic DNA using the primers. PCR products were electrophoresed in 2.0% agarose gels containing 0.5 mg/ml ethidium bromide, visualised with ultraviolet (UV) illumination and captured on Polaroid film.Results1. There are 36 cases with the CJ-IgM positve among the 56 cases GBS patients. The positve rate is 64.5%. It is very high than the CJ-IgM positve rate(17.9%) of among the healthy Controls(P<0.01).2. The rate of demylination and axon degeneration among the GBS patients and CJ-IgM positve GBS patients are similar (P>0.05).3. The serum lerev of CJ-IgM of the serious subgroup of GBS patients shows significantly higher serum level than the mild subgroup (P<0.05).4. Among the GBS patients, There are 2 cases with the genotype CD1A01/01, 7 cases with the genotype CD1A01/02,47 cases with the genotype CD1A02/02. Among the healthy Controls, There are 8 cases with the genotype CD1A01/01,21 cases with the genotype CD1A01/02,38 cases with the genotype CD1A02/02. The genotype CD1A01/02 is more frequent in healthy controls and the difference is statistically significant, the frequencies of CD1A01 allele decreased significantly in GBS patients compared with those of healthy controls. Among the CJ-IgM positve GBS patients, the genotype the frequencies of CD1A01 allele also decreased significantly more than those in healthy controls (P<0.05).5. Among the GBS patients, There are 18 cases with the genotype CD1E01/01,28 cases with the genotype CD1E01/02,10 cases with the genotype CD1E02/02. Among the healthy Controls, There are 27 cases with the genotype CD1E01/01,31 cases with the genotype CD1E01/02,9 cases with the genotype CD1E02/02. There was no significant difference in the frequency of CD1E genotypes between the GBS group and CJ-IgM positve GBS group and the group of healthy controls. The CD1E gene presents two alleles with approximately the same frequency in healthy controls and GBS patients and CJ-IgM positve GBS patients (P>0.05).Conclusion1. Campylobacter Jejuni (CJ) is one of main trigger facters of GBS.2. The serum lerev of CJ-IgM of GBS patients shows relative to the serious degree of GBS.3. CD1A and GBS(1) There are Polymorphism of CD 1A gene in GBS and healthy controls. (2) The frequencies of CD1A01 allele decreased significantly in GBS patients compared with those of healthy controls. The genotype CD1A01/01 and CD1A01/02 is more frequent in healthy controls.(3) Those might suggest that the CD1A01 allele Polymorphism of CD1A gene exon2-51-is associated with GBS and may act as a protective gene.4. CD1E and GBS(1) There are Polymorphism of CD1E gene in GBS group and healthy controls group.(2) There are no significant difference in the frequency of CD1E alleles between the GBS group and the group of healthy controls.(3) Those suggests that CD IE gene is not associated with Susceptibility to Guillain-Barre syndrome.The CD1A 01 allele might confer risk for the development of GBS through affecting interactions withβ2-microglobulin or accessory molecules.