Polymorphisms of HLA class II genes and autoimmune responses to Ro/SS-A-La/SS-B among Japanese subjects.
OBJECTIVE
To investigate HLA class II allele associations with autoantibody responses to Ro/SS-A and La/SS-B among Japanese subjects.


METHODS
Haplotype and allele distributions, along with molecular polymorphisms, of HLA class II genes were analyzed by polymerase chain reaction-restriction fragment length polymorphism in 41 Japanese women with precipitating autoantibodies to Ro/SS-A and/or La/SS-B.


RESULTS
Among women with both Ro/SS-A and La/SS-B antibodies, the HLA class II haplotype DRB1*08032/DQA1*0103/DQB1*0601 and DRB1*08032 allele showed significantly increased frequencies compared with patients with anti-Ro/SS-A alone or with normal controls. All women with both anti-Ro/SS-A and anti-La/SS-B, but not those with anti-Ro/SS-A alone, carried DRB1 alleles that shared the same amino acid residues at positions 14-31 and 71 of the hypervariable regions of the DRB1 chain. All anti-Ro/SS-A positive women carried 1 or 2 alleles of DQB1*06 and DQB1*03 subtypes that shared the same amino acid residues at positions 71-77 of the DQB1 chain. HLA class II allele distributions did not differ among 3 anti-Ro/SS-A positive groups with different disease expressions, i.e., patients with systemic lupus erythematosus, patients with primary Sjögren's syndrome, and women with no apparent symptoms of rheumatic disease.


CONCLUSIONS
HLA class II allele distributions differ among anti-Ro/SS-A positive subjects according to the presence or absence of coexisting anti-La/SS-B antibodies, but not according to disease expression. Our findings suggest that different HLA class II molecules might control the development of anti-Ro/SS-A and/or anti-La/SS-B antibodies in the autoimmune response to the Ro/SS-A-La/SS-B complex.
Miyagawa
S
S
Nara Medical University, Kashihara City, Japan.
Shinohara
K
K
Nakajima
M
M
Kidoguchi
K
K
Fujita
T
T
Fukumoto
T
T
Yoshioka
A
A
Dohi
K
K
Shirai
T
T
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D001323:Autoantibodies / Q000032:analysis*; D001324:Autoantigens / Q000276:immunology*; D005260:Female; D005802:Genes, MHC Class II / Q000235:genetics; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D006801:Humans; D007564:Japan; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology*; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D020733:RNA, Small Cytoplasmic; D012261:Ribonucleoproteins / Q000276:immunology*; D012859:Sjogren's Syndrome / Q000235:genetics / Q000276:immunology*; D000097585:SS-B Antigen; D000099207:SS-A Antigen
D001323:Autoantibodies; D001324:Autoantigens; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D020733:RNA, Small Cytoplasmic; D012261:Ribonucleoproteins; D000097585:SS-B Antigen; D000099207:SS-A Antigen; C116006:RO60 protein, human