Cytotoxicity responses to peptide antigens in rheumatoid arthritis and ankylosing spondylitis.
OBJECTIVE
To measure levels of IgG antibodies against structurally related synthetic peptides of HLA-DRB1*0404, type XI collagen, and Proteus mirabilis in patients with rheumatoid arthritis (RA) and HLA-B*2705 and Klebsiella pneumoniae in patients with ankylosing spondylitis (AS), and to determine whether sera from RA and AS patients are cytotoxic for sheep red blood cells (SRBC) coated with HLA-DRB1*0404, type XI collagen, or HLA-B*2705.


METHODS
Sera from 51 patients with RA, 34 with AS, and 38 healthy controls were tested against synthetic EQRRAA, ESRRAL, LRREI, and IRRET peptides by ELISA. Sera from patients and controls were also tested for reactivity in complement mediated cytotoxicity with SRBC coated with EQRRAA and HLA-B*2705, LRREI peptides.


RESULTS
Antibodies to synthetic peptides containing EQRRAA, ESRRAL, LRREI, and IRRET were significantly increased in RA patients compared with AS patients (p < 0.001) and controls (p < 0.001). The percentage lysis data for SRBC coated with EQRRAA and LRREI peptides were significantly higher for RA sera (p < 0.001) compared to control sera. Percentage lysis for SRBC coated with HLA-B*2705 peptide was significantly higher for AS sera (p < 0.001) compared to control sera.


CONCLUSIONS
Our results suggest that antibodies against antigenic determinants of P. mirabilis in RA and K. pneumoniae in AS have cytotoxic properties on structurally related host proteins. These cytotoxic antibodies together with T cell interactions could be relevant in the etiopathogenesis of RA and AS.
Division of Life Sciences, Infection and Immunity Group, King's College London, London, England.
Clyde
C
Wilson
Taha
T
Rashid
Harmale
H
Tiwana
Huryia
H
Beyan
Lucy
L
Hughes
Sukvinder
S
Bansal
Alan
A
Ebringer
Allen
A
Binder
D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis / Q000276:immunology; D000918:Antibody Specificity; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000382:microbiology; D001426:Bacterial Proteins / Q000138:chemical synthesis / Q000276:immunology*; D024161:Collagen Type XI / Q000276:immunology; D003167:Complement Activation; D003601:Cytotoxicity Tests, Immunologic; D004912:Erythrocytes / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology; D059811:HLA-DRB1 Chains; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis / Q000276:immunology; D007711:Klebsiella pneumoniae / Q000276:immunology; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology; D011513:Proteus mirabilis / Q000276:immunology; D012756:Sheep; D013167:Spondylitis, Ankylosing / Q000276:immunology* / Q000382:microbiology
D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D024161:Collagen Type XI; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D007074:Immunoglobulin G; D010446:Peptide Fragments