Immune responses to interphotoreceptor retinoid-binding protein and S-antigen in Behcet's patients with uveitis.
OBJECTIVE
Immune responses to retina-specific autoantigens, including S antigen (S-Ag) and interphotoreceptor retinoid binding protein (IRBP), have been suggested to be involved in the pathogenesis of human uveitis, including Behçet's disease (BD). In this study, the authors examined whether immune responses to IRBP and S-Ag in BD patients can be characterized by cytokine production profiles.


METHODS
Peripheral blood mononuclear cells (PBMCs) were collected from BD patients with uveitis and healthy controls, and each sample was cultured with IRBP, S-Ag, or purified protein derivative (PPD). At the end of culture, IL-2, IL-4, IL-6, IL-10, IL-17, IFN-gamma, and TNF-alpha concentrations in supernatants were measured.


RESULTS
PBMCs from BD patients and healthy controls produced IL-6, IL-10, IL-17, IFN-gamma, and TNF-alpha on stimulation with IRBP or S-Ag, as well as PPD stimulation, immunity against which was acquired by Bacille Calmette-Guérin immunization. IL-17 and IFN-gamma production was significantly higher when PBMCs were stimulated with IRBP than with S-Ag, whereas the reverse was observed for IL-6 production. IRBP-stimulated IL-6, IFN-gamma, and IL-17 production was higher in BD patients than in healthy controls, though IL-10 production was not different between them. In particular, IRBP-stimulated IFN-gamma production was significantly higher in BD patients with active uveitis than in BD patients with uveitis in remission.


CONCLUSIONS
Immune responses to both IRBP and S-Ag were observed even in PBMCs of healthy controls. However, the present results suggested that retinal autoantigen-stimulated IL-6, IL-17, and especially IFN-gamma production would be involved in the development of uveitis in BD.
Takeuchi
Masaru
M
Department of Ophthalmology, Tokyo Medical University, Tokyo, Japan. takeuchi@tokyo-med.ac.jp
Usui
Yoshihiko
Y
Okunuki
Yoko
Y
Zhang
Lina
L
Ma
Juan
J
Yamakawa
Naoyuki
N
Hattori
Takaaki
T
Kezuka
Takeshi
T
Sakai
Jun-ichi
J
Goto
Hiroshi
H
D056704:Adaptive Immunity; D000328:Adult; D019393:Arrestin / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D001528:Behcet Syndrome / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D005136:Eye Proteins / Q000276:immunology*; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D020381:Interleukin-17 / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D012177:Retinol-Binding Proteins / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014605:Uveitis / Q000276:immunology*; D000099214:Retinol-Binding Proteins, Interstitial
D019393:Arrestin; D001324:Autoantigens; D016207:Cytokines; D005136:Eye Proteins; D020381:Interleukin-17; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial