Differential Distribution of HLA-DQbeta/DRbeta Epitopes in the Two Forms of Guillain-Barre Syndrome, Acute Motor Axonal Neuropathy and Acute Inflammatory Demyelinating Polyneuropathy (AIDP): Identification of DQbeta Epitopes Associated with Susceptib

摘要

Guillai-Barre syndrome (GBS), an acute, immune-mediated paralytic disorder affecting the peripheral nervous sysetm, is the most common cause of acute flacid 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 undstand the pathogenesis of GBS and host susceptibility to developing the disease, the distribution fo 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 distribuitohn of class II alleles. We found that the DQbeta RLD~(55-57)/ED~(70-71) and DRbetaE~9V~11H~13 epitopes were asociated with susceptibility to AIDP (p = 0.009 and p = 0.004, resepctively), and the DQbeta RPD~(55-57) epotope was associated with proction (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 tother diseases that have a pathoimmunological basis. Class II HLA associations were not identified with AMAN, suggesting a different immunolgical mechanism of disease induction in the two forms of GBS. These findings rpovide 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.