Inflammatory disease in HLA-B27 transgenic rats.
A spontaneous inflammatory disease in rats transgenic for HLA-B27 resembles the B27-associated human spondyloarthropathies. Colitis and arthritis, the two most important features, require T cells, gut bacteria, and high expression of B27 in bone marrow-derived cells. Control rats with HLA-B7 remain healthy. Most rats with HLA-Cw6 (associated with psoriasis vulgaris) remain healthy; a minority develop mild and transient disease. Rats with a mutant B27 with a Cys67-->Ser substitution resemble wild-type B27 transgenics, but with a lower prevalence of arthritis. A similar phenotype is seen in B27 rats co-expressing a viral peptide that binds B27. Disease-prone LEW but not F344 B27 rats develop high serum IgA levels concurrent with disease progression. Colitis is associated with high interferon-gamma, arthritis with high interleukin-6. Disease is similar in B27 LEW, F344, and PVG rats, but the DA background is protective.


CONCLUSIONS
The spondyloarthropathy-like disease in rats is specific for HLA-B27 but does not require Cys67. Arthritis but not colitis is particularly sensitive to B27 peptide-binding specificity. Genetic background exerts a strong influence, but some phenotypic differences exist between permissive strains that do not influence disease susceptibility. The data favor a role for B27 peptide presentation in arthritis, but other mechanisms to explain the role of B27 have not been excluded.
Taurog
J D
JD
Harold C. Simmons Arthritis Research Center, University of Texas Southwestern Medical Center, Dallas 75235-8884, USA. joel.taurog@email.swmed.edu
Maika
S D
SD
Satumtira
N
N
Dorris
M L
ML
McLean
I L
IL
Yanagisawa
H
H
Sayad
A
A
Stagg
A J
AJ
Fox
G M
GM
Lê O'Brien
A
A
Rehman
M
M
Zhou
M
M
Weiner
A L
AL
Splawski
J B
JB
Richardson
J A
JA
Hammer
R E
RE
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D017951:Antigen Presentation; D001168:Arthritis / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D015796:HLA-B27 Antigen / Q000235:genetics*; D006801:Humans; D007111:Immunity, Cellular; D007070:Immunoglobulin A / Q000097:blood; D007249:Inflammation / Q000235:genetics* / Q000276:immunology*; D009154:Mutation; D010455:Peptides / Q000235:genetics / Q000276:immunology; D010641:Phenotype; D051381:Rats; D011919:Rats, Inbred Strains; D013166:Spondylitis / Q000235:genetics / Q000276:immunology
D016207:Cytokines; D015796:HLA-B27 Antigen; D007070:Immunoglobulin A; D010455:Peptides