Differential distribution of HLA-DQ beta/DR beta epitopes in the two forms of Guillain-Barré syndrome, acute motor axonal neuropathy and acute inflammatory demyelinating polyneuropathy (AIDP): identification of DQ beta epitopes associated with susceptibility to and protection from AIDP.
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 post-polio 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 DQ beta RLD(55-57)/ED(70-71) and DR beta E(9)V(11)H(13) epitopes were associated with susceptibility to AIDP (p = 0.009 and p = 0.004, respectively), and the DQ beta RPD(55-57) epitope was associated with protection (p = 0.05) from AIDP. These DQ beta/DR beta positional residues are a part of pockets 4 (DQ beta 70, 71, DR beta 13), 6 (DR beta 11), and 9 (DQ beta 56, 57, DR beta 9); 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 DR beta/DQ beta residues that may be instrumental in understanding the pathophysiology of AIDP.
Magira
Eleni E
EE
Department of Pediatrics, University of Pennsylvania School of Medicine and Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Papaioakim
Miltiadis
M
Nachamkin
Irving
I
Asbury
Arthur K
AK
Li
Chun Y
CY
Ho
Tony W
TW
Griffin
John W
JW
McKhann
Guy M
GM
Monos
Dimitri S
DS
D000208:Acute Disease; D000483:Alleles; D000595:Amino Acid Sequence; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000097:blood; D000942:Antigens, Bacterial / Q000097:blood / Q000276:immunology; D016123:Campylobacter jejuni / Q000276:immunology; D003711:Demyelinating Diseases / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D020022:Genetic Predisposition to Disease; D020275:Guillain-Barre Syndrome / Q000276:immunology* / Q000382:microbiology; D006682:HLA-DP Antigens / Q000235:genetics / Q000378:metabolism; D059868:HLA-DP beta-Chains; D006683:HLA-DQ Antigens / Q000235:genetics / Q000378:metabolism*; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics / Q000378:metabolism*; D059811:HLA-DRB1 Chains; D006650:Histocompatibility Testing; D006801:Humans; D016056:Immunodominant Epitopes / Q000235:genetics / Q000378:metabolism*; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D008969:Molecular Sequence Data; D016472:Motor Neuron Disease / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D020539:Sequence Analysis, Protein
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D006682:HLA-DP Antigens; D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D016056:Immunodominant Epitopes