title: Autoimmune retinopathy with RPE hypersensitivity and 'negative ERG' in X-linked hyper-IgM syndrome.
abstract: OBJECTIVE
  To report the clinical, electrophysiological, and immunological features of a patient with X-linked hyper-IgM immunodeficiency syndrome type 1 (HIGM1) accompanied by a novel type of autoimmune retinopathy, including retinal pigment epithelium (RPE) hypersensitivity.
  
  
  METHODS
  Comprehensive ophthalmological examinations, electrophysiological function testing, and inquiries into the immunological status of a 13-year-old presenting with subacute loss of vision in association with a molecularly confirmed diagnosis of HIGM1 were performed. The patient was genotyped by a PCR-based sequence tag content mapping strategy to define the genetic defect within the causative X-HIM gene TNFSF5. Since conventional allogenic bone marrow transplantation has been reported to cure HIGM1, a peripheral blood stem-cell transplantation was performed.
  
  
  RESULTS
  (1) The patient's reduced visual acuity included prolonged dark adaptation and visual field constriction. Electrophysiology revealed a 'negative ERG' indicating post-receptoral dysfunction. (2) Initial immunological examination of the patient's serum identified abnormal antibody activity with components of the photoreceptors and the inner nuclear layer. The patient later developed indications of RPE hypersensitivity. A massively reduced light-peak to dark-trough ratio of the EOG slow oscillations (L/D ratio) corresponded to impaired RPE-photoreceptor complex function. (3) Molecular genetic analyses revealed the patient to be nullizygous for the tumor necrosis factor ligand member 5 gene (TNFSF5; CD40LG). A large chromosomal deletion of approximately 27.6-32.3 kb in size was identified in Xq26. (4) The transplant with its associated immunomodulation appeared to worsen rather than improve the patient's condition.
  
  
  CONCLUSIONS
  The fundus appearance and electrophysiological function testing revealed indications of atypical retinal degeneration. However, the clinical course and the serological findings were consistent with those of ocular autoimmunity involving both antiretinal activity and RPE hypersensitivity. In this case, peripheral stem-cell transfusion with its associated chemotherapy failed to benefit the patient's vision; indications of autoimmunity appeared to increase following this treatment.
authors: Department of Pathophysiology of Vision and Neuroophthalmology, University Eye Hospital, Tuebingen, Germany.
authors: Andreas
authors: A
authors: Schuster
authors: Eckart
authors: E
authors: Apfelstedt-Sylla
authors: Carsten M
authors: CM
authors: Pusch
authors: Eberhart
authors: E
authors: Zrenner
authors: Charles E
authors: CE
authors: Thirkill
mesh_terms: D000293:Adolescent; D001327:Autoimmune Diseases / Q000276:immunology*; D018833:Chaperonins; D004596:Electroretinography; D040181:Genetic Diseases, X-Linked / Q000276:immunology*; D006801:Humans; D006942:Hypergammaglobulinemia / Q000276:immunology*; D006967:Hypersensitivity / Q000150:complications / Q000175:diagnosis / Q000276:immunology; D007153:Immunologic Deficiency Syndromes / Q000175:diagnosis / Q000235:genetics / Q000276:immunology*; D008297:Male; D009154:Mutation; D010857:Pigment Epithelium of Eye / Q000276:immunology*; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics; D012164:Retinal Diseases / Q000175:diagnosis / Q000276:immunology*; D014792:Visual Acuity; D014794:Visual Fields
chemical_list: C456359:PSMG2 protein, human; D011506:Proteins; D018833:Chaperonins