Abstract
Patients with retinitis pigmentosa and a group of controls were tested for their cellular immune response toward two retinal proteins, S-antigen and inter-photoreceptor retinoid-binding protein (IRBP), as well as their reaction against two synthetic peptides (“M” and “N”) derived from the sequence of S-antigen and peptide “R14”, derived from IRBP. Positive responses to the retinal antigens were found in larger proportions and with higher levels in the patient group than in the controls. The difference between the two groups was statistically significant in their response to S-antigen, but the patients reacted better than the controls against the other antigens as well. Of particular interest was the finding that several patients responded to both retinal proteins and/or to their peptides. These patients suffered from severe retinal changes and the data are thus interpreted as suggesting that the responses to the retinal antigens are secondary to these changes and to non-physiological release of retinal antigens.
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Brinkman CJJ, Broekhuyse RM (1978) Cell-mediated immunity after retinal detachment by lymphocyte stimulation. Am J Ophthalmol 86:260–265
Brinkman CJJ, Pinckers AJLG, Broekhuyse RM (1980) Immune reactivity to different retinal antigens in patients suffering from retinitis pigmentosa. Invest Ophthalmol Vis Sci 19:743–750
Caspi RR, Roberge FG, Chan CC, Wiggert B, Chader GJ, Rozenszajn LA, Lando Z, Nussenblatt RB (1988) A new model of autoimmune disease. Experimental autoimmune uveoretinitis induced in mice with two different retinal antigens. J Immunol 140:1490–1495
Chader GJ (1989) Interphotoreceptor retinoid-binding protein (IRBP): a model protein for molecular biological and clinically relevant studies. Invest Ophthalmol Vis Sci 30:7–22
De Smet MD, Yamamoto JH, Mochizuki M, Gery I, Singh VK, Shinohara T, Wiggert B, Chader GJ, Nussenblatt RB (1990) Cellular immune responses of patients with uveitis to retinal antigens and their fragments. Am J Ophthalmol 110:135–142
Donoso LA, Merryman CF, Shinohara T, Dietzschold B, Wistow G, Craft C, Morley W, Henry RT (1986) S-antigen: identification of the MabA9-C6 monoclonal antibody binding site and the uveitopathogenic sites. Curr Eye Res 5:995–1004
Donoso LA, Merryman CF, Sery TW, Shinohara T, Dietzschold B, Smith A, Kalsow CM (1987) S-antigen: characterization of a pathogenic epitope which mediates experimental autoimmune uveitis and pinealitis in Lewis rats. Curr Eye Res 6:1151–1159
Dorey C, Cozette J, Faure JP (1982) A simple and rapid method for isolation of retinal S-antigen. Ophthalmic Res 14:249–255
Gery I, Mochizuki M, Nussenblatt RB (1978) Retinal specific antigen and immunopathogenic processes they provoke. In: Osborne N, Chader GJ (eds) Progress in retinal research. Pergamon Press, New York, pp 75–109
Gregerson DS, Fling SP, Obritsch WF, Merryman CF, Donoso LA (1989) Identification of T cell recognition sites in S-antigen: dissociation of proliferative and pathogenic sites. Cell Immunol 123:427–440
Heredia CD, Vich JM, Huguet J, García-Calderón JV, García-Calderón PA (1981) Altered cellular immunity and suppressor cell activity in patients with primary retinitis pigmentosa. Br J Ophthalmol 65:850–854
Hirose S, Kuwabara T, Nussenblatt RB, Wiggert B, Redmond TM, Gery I (1986) Uveitis induced in primates by interphotoreceptor retinoid-binding protein. Arch Ophthalmol 104:1698–1702
Hirose S, Tanaka T, Nussenblatt RB, Palestine AG, Wiggert B, Redmond TM, Chader GJ, Gery I (1988) Lymphocyte responses to retinal-specific antigens in uveitis patients and healthy subjects. Curr Eye Res 7:393–402
Hirose S, Singh VK, Donoso LA, Shinohara T, Kotake S, Tanaka T, Kuwabara T, Yamaki K, Gery I, Nussenblatt RB (1989) An 18-mer peptide derived from the retinal S-antigen induces uveitis and pinealitis in primates. Clin Exp Immunol 77:106–111
Kotake S, Wiggert B, Zhang X-Y, Redmond TM, Chader GJ, Gery I (1990) Stimulation in vitro of lymphocytes for induction of uveoretinitis without any significant proliferation. J Immunol 145:534–539
Merin S, Auerbach E (1976) Retinitis pigmentosa. Surv Ophthalmol 20:303–346
Narfström K, Nilsson S-E, Wiggert B, Lee L, Chader GJ, Van Veen T (1989) Reduced level of interphotoreceptor retinoid-binding protein (IRBP), a possible cause for retinal degeneration in the Abyssinian cat. Cell Tissue Res 257:631–639
Newsome DA (1985) The immune system in retinitis pigmentosa. In: LaVail MM, Hollyfield JG, Anderson RE (eds) Retinal degeneration: experimental and clinical studies. Liss, New York, pp 75–90
Newsome DA, Nussenblatt RB (1984) Retinal S-antigen reactivity in patients with retinitis pigmentosa and Usher's syndrome. Retina 4:195–199
Nussenblatt RB, Gery I, Ballintine EJ, Wacker WB (1980) Cellular immune responsiveness of uveitis patients to retinal S-antigen. Am J Ophthalmol 89:173–179
Redmond TM, Wiggert B, Robey FA, Nguyen NY, Lewis MS, Lee L, Chader GJ (1985) Isolation and characterization of monkey interphotoreceptor retinoid-binding protein, a unique extracellular matrix component of the retina. Biochemistry 24:787–793
Richard GW (1989) Retinitis pigmentosa and allied disorders. In: Ryan SJ, Ogden TE (eds) Retina. Mosby, St. Louis, pp 300–317
Rocha H, Antunes L (1977) Primary retinitis pigmentosa —autoimmunity? Metab Ophthalmol 1:153–156
Sanui H, Redmond TM, Kotake S, Wiggert B, Hu L-H, Margalit H, Berzofsky JA, Chader GJ, Gery I (1989) Identification of an immunodominant and highly immunopathogenic determinant in the retinal interphotoreceptor retinoid-binding protein (IRBP). J Exp Med 169:1947–1960
Sanui H, Redmond TM, Kotake S, Wiggert B, Tanaka T, Chader GJ, Gery I (1990) Uveitis and immune responses in primates immunized with IRBP-derived synthetic peptides. Curr Eye Res 9:193–199
Singh VK, Nussenblatt RB, Donoso LA, Yamaki K, Chan C-C, Shinohara T (1988) Identification of a uveitopathogenic and lymphocyte proliferation site in bovine S-antigen. Cell Immunol 115:413–419
Unanue ER, Cerottini J-C (1989) Antigen presentation. FASEB J 3:2496–2502
Wacker WB, Donoso LA, Kalsow CM, Yankeelov Jr JA, Organisciak DT (1977) Experimental allergic uveitis: isolation, characterization and localization of a soluble uveitopathogenic antigen from bovine retina. J Immunol 119:1949–1958
Wood-Gush HG (1989) Retinitis pigmentosa research: a review. J R Soc Med 82:355–358
Yamamoto JH, Mochizuki M, Wiggert B, Chader GJ, Shinohara T, Gery I, Nussenblatt RB (1990) Cellular immune responsiveness of Japanese uveitis patients to retinal antigens and their uveitogenic peptides. In: Usui M, Ohno S, Aoki K (eds) Ocular immunology today. Elsevier, Amsterdam, pp 357–360
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Yamamoto, J.H., Okajima, O., Mochizuki, M. et al. Cellular immune responses to retinal antigens in retinitis pigmentosa. Graefe's Arch Clin Exp Ophthalmol 230, 119–123 (1992). https://doi.org/10.1007/BF00164648
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DOI: https://doi.org/10.1007/BF00164648