Differential distribution of HLA-DQβ/DRβ epitopes in the two forms of Guillain-Barre syndrome, acute motor axonal neuropathy and acute inflammatory demyelinating polyneuropathy (AIDP):: Identification of DQβ epitopes associated with susceptibility to and protection from AIDP

Guillain-Barre 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 11 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 11 alleles. We found that the DQbeta RLD55-57/ED70-71 and DRbeta (EVH13)-V-9-H-11 epitopes were associated with susceptibility to AIDP (p = 0.009 and p = 0.004, respectively), and the DQbeta RPD55-57 epitope was associated with protection (p = 0.05) from AIDP. These DQbeta/DRbeta positional residues are a part of pockets 4 (DQbeta 70, 71, DRbeta13), 6 (DRbeta11), and 9 (DQbeta 56, 57, DRbeta9); 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 11 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 DRbeta/DQbeta residues that may be instrumental in understanding the pathophysiology of AIDP.