title: Vogt-Koyanagi-Harada-like syndrome after CTLA-4 inhibition with ipilimumab for metastatic melanoma.
abstract: Cytotoxic T-lymphocyte-associated antigen is a naturally occurring inhibitor of T-cell costimulation. Monoclonal antibody inhibition of cytotoxic T-lymphocyte-associated antigen with ipilimumab blocks this negative regulator of costimulation, promoting T-cell activation and survival, and leads to melanoma regression. Findings of the Vogt-Koyanagi-Harada (VKH) syndrome, an uveomeningitic syndrome that features neurological, auditory, ophthalmologic, and cutaneous involvement because of autoimmune targeting of melanocytic antigen, have rarely been described in association with melanoma immunotherapy. We describe a case of VKH-like syndrome in a 45-year-old HLA-A02-positive patient with metastatic melanoma treated with ipilimumab. Disruption of immune tolerance by ipilimumab led to melanoma remission while also inciting systemic and ophthalmic autoimmunity toward melanocytic antigen. These observations provide insight into the pathophysiology of the VKH syndrome, and the balance between tumor-associated tolerance and autoimmunity.
authors: *Department of Ophthalmology, Emory Eye Center †Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA.
authors: Jason N
authors: JN
authors: Crosson
authors: Philip W
authors: PW
authors: Laird
authors: Matthew
authors: M
authors: Debiec
authors: Chris S
authors: CS
authors: Bergstrom
authors: David H
authors: DH
authors: Lawson
authors: Steven
authors: S
authors: Yeh
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity; D060908:CTLA-4 Antigen / Q000276:immunology; D005260:Female; D015789:HLA-A2 Antigen / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy; D000074324:Ipilimumab; D008544:Melanocytes / Q000276:immunology / Q000378:metabolism*; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012878:Skin Neoplasms / Q000188:drug therapy / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014607:Uveomeningoencephalitic Syndrome / Q000139:chemically induced / Q000175:diagnosis*
chemical_list: D000911:Antibodies, Monoclonal; D001324:Autoantigens; D060908:CTLA-4 Antigen; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D000074324:Ipilimumab