Detection of major histocompatibility complex/human cartilage gp‐39 complexes in rheumatoid arthritis synovitis as a specific and independent histologic marker

Abstract

Clinically, there were no correlations between mAb 12A staining and clinical or biologic parameters in RA. However, positive staining was observed in 61.5% of the inflamed RA synovial samples compared with only 3.0% of the control samples (P < 0.001). This mAb 12A staining was not related to intracellular citrullinated peptides, which are another specific histologic marker for RA.Conclusion. Presentation by synovial dendritic cells of the immunodominant epitope of HC gp-39, in the context of the shared epitope, is associated with characteristic histologic features of follicular synovitis and is highly specific for RA. This suggests a contribution to the autoimmune-related tissue inflammation and provides a new and independent tool for the immunopathologic diagnosis of RA.

Endogenous HLA–DR–restricted presentation of the cartilage antigens human cartilage gp‐39 and melanoma inhibitory activity in the inflamed rheumatoid joint

“…These enhanced local levels of HC gp-39 or MIA were not RA specific but were found to correlate more generally with arthritic disorders, since comparable levels were found in SF and ST of patients with spondylarthritis and osteoarthritis (ref. 19 and present study).…”

“…Previously we demonstrated that HC gp-39 is not expressed exclusively in articular cartilage but is found also in inflamed synovium and that the synovial membrane is a privileged site for presentation of this protein to the immune system (6,14,19). In immunohistochemistry analyses for MIA in the present study, collected biopsies described previously (14,19,29,33) were used to investigate local expression of MIA in the synovium, with mAb 14A.…”

“…Additional SF samples from RA, SpA, and osteoarthritis (OA) patients originated from a previous study (28). Synovial membrane biopsy specimens from another group of patients (described in previous reports [14,19,29]) were obtained for immunohistochemistry studies. Eight biopsy samples per patient (17 RA, 13 SpA, 6 OA), obtained from an inflamed knee joint by needle arthroscopy (30), were studied.…”

“…For immunohistochemistry, the ST sections were blocked with 10% normal human serum and incubated overnight with mAb 14A (1 g/ml). Staining was performed as described previously (14,19,29,33), using an LSABϩ kit according to the instructions of the manufacturer (DakoCytomation, Glostrup, Denmark). Parallel sections were incubated with concentration-and isotype-matched irrelevant antibody (Dako Cytomation) as a negative control.…”

“…In mice that have been immunized with HC gp-39, a mild but chronic, relapsing arthritis is induced (5). In studies of synovial tissue (ST) from patients with RA, investigators from our group (6,19) demonstrated the RA-specific presence of cells that were positive for a class II MHC-HC gp-39 peptide complex. Whether these cells functionally present HC gp-39 and can thus activate T cells in the RA joint was not examined.…”