Humoral and cellular immune responsiveness to human S-antigen in uveitis

Abstract

Purified human retinal S-antigen (S-ag) was used to investigate the occurrence of humoral and cellular autoimmune reactions against S-ag in uveitis patients. With a sensitive ELISA method anti-S-ag antibodies could be detected in the sera of 28% of the uveitis patients. No difference was found between patients with posterior or panuveitis (31 out of 117 positive) and patients with anterior or intermediate uveitis (16 out of 52 positive). Similar frequencies and levels of anti-S-ag autoantibodies were also found among healthy controls (6/20) and patients who had undergone cataract surgery (6/17). Immunoblotting with purified S-ag and with whole human retinal extract confirmed the presence of anti-S-ag antibodies in uveitis and control sera. Moreover, antibodies against various other retinal proteins could also be demonstrated in patients and controls, without being particularly enhanced in uveitis. The cellular immune responsiveness was tested by measuring the production of migration inhibitory factor (MIF) during overnight culture of peripheral mononuclear cells with the antigen. None of 18 healthy controls responded, whereas 17 positive reactions were observed in the group of 44 uveitis patients. The highest frequencies were found in patients with posterior (5/12) or pan- (7/12) uveitis, while of the responders with anterior (2/8) or intermediate (3/12) uveitis, three had disorders affecting the retina. Thus, cellular autoimmune responsiveness to S-ag is apparently associated with posterior and pan-uveitis, and might also occur in non-uveitic retinal disorders, whereas the occurrence of anti-S-ag antibodies is probably not at all pathognomic for uveitis.

Spontaneous retinopathy in HLA-A29 transgenic mice

“…The patient also had a positive proliferative response of peripheral blood lymphocytes to retinal S-antigen in vitro. Although Santigen immune response is not unique to patients with BSCR and could also occur in patients with other forms of uveitis, including nonimmune inherited retinal diseases (23), S-antigen is considered a model autoantigen in BSCR (8,(24)(25)(26)(27)(28). The general BSCR pathogenic features are similar to those observed in S-antigen-induced experimental autoimmune uveoretinitis in monkey (29,30).…”

Soluble intercellular adhesion molecule-1 (sICAM-1) as a marker of disease relapse in idiopathic uveoretinitis

“…In the clinical management of uveitis, histological examination of intraocular inflammation is rarely possible for technical and ethical reasons, and peripheral blood changes remain the only practical method of monitoring disease activity and more importantly of predicting disease relapse. Studies of immunological reactivity to retinal autoantigens have provided little correlation with disease activity thus far [5][6][7][8].…”

Definition of the HLA-A29 peptide ligand motif allows prediction of potential T-cell epitopes from the retinal soluble antigen, a candidate autoantigen in birdshot retinopathy.

“…For these alleles residue at P2 is not considered as a dominant anchor but is preferentially occupied by an hydrophobic or aromatic residue. Although S-Ag immune response is not unique to patients with BSR and could also occur in patients with other forms of uveitis, S-Ag is considered a model autoantigen in this disease (1,9,(11)(12)(13) and is highly uveitogenic in animal models (9). For that reason, we synthesized S-Ag peptides in accordance with the HLA-A29 motif, which were tested in the in vitro refolding assay.…”

“…9) upon immunization with retinal evolutionary conserved autoantigens: retinal soluble antigen (S-Ag) and interphotoreceptorretinoid-binding protein. S-Ag can also induce EAU in primates (10) and elicits proliferative cellular responses in some BSR affected individuals (11)(12)(13). It is a 48-kDa dominant…”