Cellular immunity to cartilage link protein in patients with inflammatory arthritis and non-arthritic controls.
OBJECTIVE
To determine if increased T cell responses to articular cartilage link protein have any correlation with rheumatoid arthritis (RA), and if RA patients with increased responses to link protein also respond to a 17 amino acid peptide covering the 'arthritogenic' epitope in mycobacterial hsp65 which is homologous with link protein.


METHODS
The reactivity of T cells from both peripheral blood and synovial fluid, to highly purified human cartilage link protein, hsp65, the 17 amino acid peptide, and bovine type II collagen was determined in patients with RA and nonarthritic controls, by measuring the rate of mononuclear cell proliferation in the presence and absence of antigen.


RESULTS
Using peripheral blood mononuclear cells (PBMC), significant reactivity (stimulation index (SI) > 1.5) to link protein was found in 12 of 46 RA patients (26%), but in only four of 44 controls (9%). A greater proportion of RA patients (eight of 17:47%) were reactive to link protein when mononuclear cells from synovial fluid were tested. SI values, however, were generally low (0.5-3.1) and only one patient showed a PBMC response above a reference range of values calculated from the logarithmic values of the normal control population. No reactivity was observed against a 17 amino acid synthetic peptide including the arthritogenic epitope from the mycobacterial hsp65 to which T cell clones isolated from rats in the adjuvant arthritis model react. However, eight of nine RA patients and all of seven controls reacted to the intact hsp65.


CONCLUSIONS
It remains unclear if T cell responses to link protein are involved in the pathogenesis of RA, but it is unlikely that T cells specific for the sequence homologous with the arthritogenic epitope in hsp65 are present in RA patients.
Doran
M C
MC
Department of Rheumatology, Robert Jones and Agnes Hunt Orthopaedic and District Hospital, NHS Trust, Oswestry, Shropshire, United Kingdom.
Goodstone
N J
NJ
Hobbs
R N
RN
Ashton
B A
BA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000942:Antigens, Bacterial / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001426:Bacterial Proteins; D002455:Cell Division; D002478:Cells, Cultured; D018834:Chaperonin 60; D018833:Chaperonins / Q000276:immunology; D016326:Extracellular Matrix Proteins; D006801:Humans; D007111:Immunity, Cellular; D008875:Middle Aged; D011506:Proteins / Q000276:immunology*; D011509:Proteoglycans / Q000276:immunology*; D013582:Synovial Fluid / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D000099249:Proteoglycan Link Protein
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D018834:Chaperonin 60; D018833:Chaperonins; D016326:Extracellular Matrix Proteins; D011506:Proteins; D011509:Proteoglycans; D000099249:Proteoglycan Link Protein; C074119:heat-shock protein 65, Mycobacterium