title: An altered immune response to Epstein-Barr nuclear antigen 1 in pediatric systemic lupus erythematosus.
abstract: OBJECTIVE
  New examples support the concept that host immune responses to pathogenic organisms can act as the nidus for autoimmunity. Two such examples implicate the Epstein-Barr virus (EBV) in systemic lupus erythematosus (SLE), i.e., data consistent with SLE anti-Sm and anti-60-kd Ro autoantibodies emerging from distinct humoral immune responses to Epstein-Barr nuclear antigen 1 (EBNA-1). We undertook this study to further test whether the humoral immune response to EBNA-1 is a risk factor for pediatric SLE.
  
  
  METHODS
  Sera from pediatric lupus patients and healthy matched controls were tested for anti-EBNA-1 by Western blotting and enzyme-linked immunosorbent assay (ELISA). To define the fine specificity of their anti-EBNA-1 humoral immune response, fragments of EBNA-1 and the maximally overlapping unique octapeptides of EBNA-1 were tested by modified ELISAs.
  
  
  RESULTS
  All 36 pediatric SLE patient sera tested recognized EBNA-1, while sera from only 25 of 36 matched EBV-positive controls targeted EBNA-1 (P < 0.005). Epitope mapping revealed that the humoral anti-EBNA-1 response in pediatric SLE was distinct from and less restricted than that in matched normal individuals. Meanwhile, no significant differences between SLE patient sera and control sera were observed in the responses to other herpesviruses or in binding to sequential epitopes from cytomegalovirus immediate-early antigen or EBNA-2.
  
  
  CONCLUSIONS
  Anti-EBNA-1 antibodies are associated with pediatric-onset SLE. Furthermore, an altered humoral immune response to EBNA-1, characteristic of SLE, has been found and may be an important SLE susceptibility factor.
authors.affiliation: Oklahoma Medical Research Foundation and University of Oklahoma Health Sciences Center, 825 NE 13th Street, Oklahoma City, OK 73104, USA.
authors.forename: Micah T
authors.initials: MT
authors.lastname: McClain
authors.forename: Brian D
authors.initials: BD
authors.lastname: Poole
authors.forename: Benjamin F
authors.initials: BF
authors.lastname: Bruner
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Kaufman
authors.forename: John B
authors.initials: JB
authors.lastname: Harley
authors.forename: Judith A
authors.initials: JA
authors.lastname: James
mesh_terms: D000293:Adolescent; D002648:Child; D000939:Epitopes / Q000276:immunology; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology*; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008297:Male; D012307:Risk Factors
chemical_list: D000939:Epitopes; D019309:Epstein-Barr Virus Nuclear Antigens