Cellular Immune Responses of Patients with Uveitis to Retinal Antigens and Their Fragments

Smet, Marc D. de; Yamamoto, Joyce Hisae; Mochizuki, Manabu; Gery, Igal; Singh, Vijay K.; Shinohara, Toshimichi; Wiggert, Barbara; Chader, Gerald J.; Nussenblatt, Robert B.

doi:10.1016/s0002-9394(14)76981-8

Cited by 155 publications

(71 citation statements)

References 23 publications

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“…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).…”

Section: Resultsmentioning

confidence: 99%

Spontaneous retinopathy in HLA-A29 transgenic mice

Szpak

Vieville

Tabary

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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Humans who have inherited the class I major histocompatibility allele HLA-A29 have a markedly increased relative risk of developing the eye disease termed birdshot chorioretinopathy. This disease affecting adults is characterized by symmetrically scattered, small, cream-colored spots in the fundus associated with retinal vasculopathy and inflammatory signs causing damage to the ocular structures, leading regularly to visual loss. To investigate the role of HLA-A29 in this disease, we introduced the HLA-A29 gene into mice. Aging HLA-A29 transgenic mice spontaneously developed retinopathy, showing a striking resemblance to the HLA-A29-associated chorioretinopathy. These results strongly suggest that HLA-A29 is involved in the pathogenesis of this disease. Elucidation of the role of HLA-A29 should be assisted by this transgenic model.

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Section: Resultsmentioning

confidence: 99%

Spontaneous retinopathy in HLA-A29 transgenic mice

Szpak

Vieville

Tabary

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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“…One example is the retinal S antigen, a retinal protein that is found only after tissue destruction following uveitis and triggers T-cell response. 31 One epitope of this protein is similar to HLA-B51 and -B27, the latter being another gene associated with uveitis. 32,33 It is likely that these proteins, once released, support and feed chronic uveitis.…”

Section: Discussionmentioning

confidence: 99%

Ocular involvement is associated with HLA-B51 in Adamantiades–Behçet's disease

Krause

Altenburg

et al. 2008

Eye

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Purpose To evaluate the association of HLA-B51 and ocular involvement in Adamantiades-Behçet's disease. Methods We retrospectively analysed all patients with Adamantiades-Behçet's disease examined in our Department of Ophthalmology since 1982. All patients fulfilled the criteria of the International Study Group for Behçet's disease. We included 140 patients (63 female and 77 male) with a mean follow-up of 6.4 years. Results The mean age at the first manifestation was 23 years; full disease was noted at 32 years. The mean age at the time of eye involvement was 30 years. Most of the patients were of Turkish (n ¼ 73) or German (n ¼ 34) origin. A total of 56% patients developed eye involvement. Forty-nine out of 76 HLA-B51-positive patients (64.5%) and 26 out of 60 HLA-B51-negative patients (43.3%; P ¼ 0.014) developed ocular involvement. Conclusion More than the half of the patients with Adamantiades-Behçet's disease evaluated in our department developed ocular involvement. There was a statistically significantly higher frequency of HLA-B51 in these patients.

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“…Data compiled from de Smet et al 3,17 Ϯ indicates 25%-49% of individuals showed a 2-fold increase in lymphocyte proliferation to Ն 50 g/mL of peptide or protein; Ϫ, no response observed; and ϩ, 50% or more individuals showed a 2-fold increase in lymphocyte proliferation to Ն 50 g/mL of peptide or protein.…”

Section: Discussionmentioning

confidence: 99%

“…There was no detectable migration of human leukocytes to peptides 1-20 or 161-180 of human IRBP, (which are uveitogenic in C57BL/6 mice and B10.RIII mice, respectively), in a 1 to 10 000-ng/mL range. Chemotactic responses were observed with lymphocytes isolated from healthy controls to S-Ag peptides corresponding to amino acids 1-20, 11-30, 41-60, 121-140, and 131-150 (Table 3), 3,17 but peptides corresponding to human S-Ag amino acids 141-160, 151-170, 161-180, and 171-190 did not induce migration when tested in the 1 to 1000-ng/mL range. Combined with data from published literature, our observations suggest that, unlike HisRS, S-Ag has multiple and distinct epitopes responsible for chemotaxis, leukocyte proliferation, and elicitation of autoantibodies (Table 3).…”

Section: Lymphocyte Proliferation Eau Pathology and Chemoattractionmentioning

confidence: 99%

“…Uveitis patients present with detectable antibodies and lymphocyte proliferation to these antigens. [3][4][5][6][7] Autoimmune uveitis is thought to be primarily mediated by CD4 ϩ T cells with a T-helper 1 (Th1)-like lymphokine profile in human disease and in animal models. 2,8,9 IRBP and S-Ag can induce experimental autoimmune uveitis (EAU) in rodent models.…”

Section: Introductionmentioning

confidence: 99%

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Autoantigens signal through chemokine receptors: uveitis antigens induce CXCR3- and CXCR5-expressing lymphocytes and immature dendritic cells to migrate

Howard

Dong

et al. 2005

Blood

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We tested the hypothesis that interaction between autoantigens and chemoattractant receptors may be an important step in the development of autoimmunity. The retinal autoantigens S-antigen (S-Ag) and interphotoreceptor retinoid binding protein (IRBP) can induce autoimmune uveitis in rodent models. We evaluated the chemotactic activity of S-Ag and IRBP and found that both induced migration of human and mouse immature dendritic

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Cellular Immune Responses of Patients with Uveitis to Retinal Antigens and Their Fragments

Cited by 155 publications

References 23 publications

Spontaneous retinopathy in HLA-A29 transgenic mice

Spontaneous retinopathy in HLA-A29 transgenic mice

Ocular involvement is associated with HLA-B51 in Adamantiades–Behçet's disease

Autoantigens signal through chemokine receptors: uveitis antigens induce CXCR3- and CXCR5-expressing lymphocytes and immature dendritic cells to migrate

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