TY - JOUR
T1 - 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)
T2 - Identification of DQβ epitopes associated with susceptibility to and protection from AIDP
AU - Magira, Eleni E.
AU - Papaioakim, Miltiadis
AU - Nachamkin, Irving
AU - Asbury, Arthur K.
AU - Li, Chun Y.
AU - Ho, Tony W.
AU - Griffin, John W.
AU - McKhann, Guy M.
AU - Monos, Dimitri S.
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2003/3/15
Y1 - 2003/3/15
N2 - 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 E9VH11H13 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.
AB - 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 E9VH11H13 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.
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U2 - 10.4049/jimmunol.170.6.3074
DO - 10.4049/jimmunol.170.6.3074
M3 - Article
C2 - 12626563
AN - SCOPUS:0347927276
SN - 0022-1767
VL - 170
SP - 3074
EP - 3080
JO - Journal of Immunology
JF - Journal of Immunology
IS - 6
ER -