Anti-MHC autoimmunity in Behçet’s disease: T cell responses to an HLA-B-derived peptide cross-reactive with retinal-S antigen in patients with uveitis

Abstract

SUMMARYImmune response to retinal autoantigens plays a central role in the pathogenesis of uveitis. A synthetic peptide (B27PD) from a common sequence of various HLA-B molecules associated with uveitis, such as HLA-B27 and 51, which shares amino acid homologies with a retinal-S antigen (S-Ag)-derived peptide (PDSAg), was shown to be immunogenic in human and experimental uveitis in the rat. In this study we investigated T cell responses to B27PD and PDSAg in patients with Behc Ëet's disease and posterior uveitis (BD-posterior uveitis; n 33) in comparison with non-Behc Ëet anterior uveitis (AU, n 14), Behc Ëet's patients without uveitis (BD, n 15) and healthy controls (HC, n 32) in a 6-day proliferation assay. Patients with BD and posterior uveitis had significantly higher responses (stimulation index (SI) 2´8^1´3) than those with AU (SI 1´5^0´4), BD without uveitis (SI 1´1^0´4) and HC (SI 1´1^0´6) for B27PD (P , 0´0001). Responses to PDSAg were also higher in BD with posterior uveitis patients (SI 3´3^1´6) than AU (SI 1´5^0´4), BD without uveitis (SI 1´2^0´3) and HC (SI 1´1^0´6) (P , 0´0001). A significant correlation between the responses to PDSAg and B27PD (r 0´56, P , 0´001) was observed. Elevated levels of IL-2 and tumour necrosis factor-alpha were also observed in culture supernatants obtained from peripheral blood mononuclear cells after stimulation with the peptides, but no correlation was found between the proliferative responses and cytokine levels. These results suggest that cellular immunity to cross-reactive HLA-B and S-Ag-derived peptides might play a role in the pathogenesis of posterior uveitis in BD.

Behcet's disease: infectious aetiology, new autoantigens, and HLA-B51

“…Development of uveitis in rats by both peptides is supportive of this model 71. T cell responses to these uveitogenic peptides were first shown in German patients with uveitis,71 and recently confirmed in a larger group of patients with BD from Turkey 74…”

Chemokine Expression of Intraocular Lymphocytes in Patients with Behçet Uveitis

“…Ocular involvement commonly results in bilateral blindness despite the use of a potent immunosuppressant. Though the underlying immunopathogenic mechanisms are unclear, dysfunction of the innate and adaptive immune responses against infectious agents and autoantigens appears to be involved in the pathogenesis of Behçet uveitis [1][2][3] . We have demonstrated that the immune effectors in Behçet uveitis are distinguished from those in other causes of endogenous uveitis [4][5][6] .…”

Down-Regulation of IFN-γ–Producing CD56+T Cells after Combined Low-Dose Cyclosporine/Prednisone Treatment in Patients with Behçet’s Uveitis

“…[2][3][4] Both innate and adaptive immune responses have been suggested to play a pathogenic role in Behçet's disease. 5,6 Aberrant cellular immunity, such as T-cell-mediated autoimmunity or an imbalance in the Th1/Th2 pathway, may be crucial in the pathogenesis of Behçet's disease. 7,8 Recently, CD56 ϩ T cells were reported to be higher in the aqueous humor and peripheral blood of patients with Behçet's uveitis than were other endogenous uveitides.…”