Differential Distribution of HLA-DQβ/DRβ Epitopes in the Two Forms of Guillain-Barré Syndrome, Acute Motor Axonal Neuropathy and Acute Inflammatory Demyelinating Polyneuropathy (AIDP): Identification of DQβ Epitopes Associated with Susceptibility to and Protection from AIDP

Abstract

Guillain-Barré syndrome (GBS), an acute, immune-mediated paralytic disorder affecting the peripheral nervous system, is the most common cause of acute flaccid paralysis in the postpolio era. GBS is classified into several subtypes based on clinical and pathologic criteria, with acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN) being the most common forms observed. To better understand the pathogenesis of GBS and host susceptibility to developing the disease, the distribution of HLA class II Ags along with the seroreactivity to Campylobacter jejuni were investigated in a population of GBS patients from northern China. Using DNA-based typing methods, 47 patients with AMAN, 25 patients with AIDP, and 97 healthy controls were studied for the distribution of class II alleles. We found that the DQβ RLD55–57/ED70–71 and DRβ E9V11H13 epitopes were associated with susceptibility to AIDP (p = 0.009 and p = 0.004, respectively), and the DQβ RPD55–57 epitope was associated with protection (p = 0.05) from AIDP. These DQβ/DRβ positional residues are a part of pockets 4 (DQβ 70, 71, DRβ13), 6 (DRβ11), and 9 (DQβ 56, 57, DRβ9); have been demonstrated to be important in peptide binding and T cell recognition; and are associated with other diseases that have a pathoimmunological basis. Class II HLA associations were not identified with AMAN, suggesting a different immunological mechanism of disease induction in the two forms of GBS. These findings provide immunogenetic evidence for differentiating the two disease entities (AMAN and AIDP) and focuses our attention on particular DRβ/DQβ residues that may be instrumental in understanding the pathophysiology of AIDP.

Association of Tumor Necrosis Factor Polymorphisms with Guillain-Barré Syndrome

“…There was a significant association with HLA DQB1*03 in British C. jejuni -associated GBS [12], but this link was not noted in Dutch or Japanese studies [13, 14]. Most recently, in northern Chinese patients with AIDP, strong positive associations were found with particular DQβ and DQβ positional residues, and a weak negative association was found with another DQβ residue [15]. No association between AMAN and any HLA class II alleles was noted in the same study, supporting the view that AMAN has a different pathogenetic mechanism from AIDP.…”

Ganglioside mimicry and peripheral nerve disease

“…The occurrence of GBS within families suggests that host susceptibility also is important. 19 Previous attempts to identify common host immunogenetic factors in C. jejuni-related GBS patients, however, were negative or diverse for HLA typing, 20,56,83,106 T-cellreceptor genotyping, 82 and polymorphism analysis of CD14 and Toll-like receptor 4. A genome-wide search of single nucleotide polymorphisms might identify host susceptibility genes in GBS and FS subsequent to C. jejuni enteritis.…”

SKDM human leukocyte antigen (HLA) tool: A comprehensive HLA and disease associations analysis software

“…The SKDM software was tested for validation against two previously published studies [14,15]. The complete analysis for one of them [14] has been included as an electronic supplement to the current paper.…”