Autoantibodies to p75/LEDGF, a cell survival factor, found in patients with atypical retinal degeneration.
We have identified a group of patients with an atypical retinal degeneration having anti-retinal autoantibodies in their sera. This select population is characterized by a progressively severe loss of vision associated with a decrease in photoreceptor function, abnormal pigmentation of the retinal pigment epithelium and a negative family history of retinal dystrophy. Immunohistochemical analysis on mouse retinal tissues with sera from this group of patients demonstrated high titers of anti-retinal antibodies (320 to 1,280). Anti-retinal reactivity at these levels was not detected in sera from normal individuals, or from patients with uveitis or known genetic retinal degenerations. One antigen that was identified from a retina cDNA library with sera from a patient with atypical retinal degeneration was lens epithelium-derived growth factor (LEDGF). Western blot analysis revealed that sera from all three patients demonstrated reactivity to p75/LEDGF, a survival factor that protects cells from oxidative, thermal and UV damage. In conclusion, we have found a novel group of patients with a retinal degeneration of non-paraneoplastic, non-familial origin demonstrating immunoreactivity to an autoantigen, p75/LEDGF, heretofore not associated with this disease. Finally, identification of specific anti-retinal antibodies may have applications in the diagnosis and management of retinal degeneration.
Chin
Marian S
MS
Immunology and Virology Section, Laboratory of Immunology, National Eye Institute, National Institutes of Health, 10 Center Drive, Building 10, Room 10N248, Bethesda, MD 20892, USA.
Caruso
Rafael C
RC
Detrick
Barbara
B
Hooks
John J
JJ
D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D001323:Autoantibodies / Q000032:analysis / Q000097:blood*; D002470:Cell Survival / Q000276:immunology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008875:Middle Aged; D012160:Retina / Q000276:immunology*; D012162:Retinal Degeneration / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D014157:Transcription Factors / Q000276:immunology*
D048868:Adaptor Proteins, Signal Transducing; D001323:Autoantibodies; C504649:PSIP1 protein, human; D014157:Transcription Factors