Nonantibestrophin Anti-RPE Antibodies in Paraneoplastic Exudative Polymorphous Vitelliform Maculopathy

A previous report demonstrated antibodies to bestrophin in paraneoplastic exudative polymorphous vitelliform maculopathy (PEPVM). Other cases demonstrated antibodies to different proteins in the retinal pigment epithelium (RPE). In this report, serum was analyzed to determine whether a patient with PEPVM and a reduced Arden ratio had developed autoantibodies to human Bestrophin-1 (Best1).

Human embryonic kidney 293 cells (HEK293) were transfected with Best1 and stained with an antibody specific to Best1 (E6-6), or patient serum. Staining patterns were compared with those of untransfected cells stained with E6-6, patient serum, control serum, or secondary antibody alone. Western blots were performed using lysed RPE and stained with E6-6, patient serum, control serum, or secondary antibody alone.

Immunofluorescence staining of HEK-293 cells or HEK-293 cells expressing Best1 did not differ between patient and control sera or show a staining pattern consistent with recognition of Best1. Immunoblotting of human RPE lysate with patient serum did not identify Best1 (68 kDa) but did recognize a band at approximately 48 kDa that was absent in blots using control serum.

To our knowledge, this is the first report of PEPVM with an autoantibody to an approximately 48-kDa RPE protein, but previous reports have demonstrated autoantibodies to other RPE proteins, suggesting that autoantibody formation is an important component of PEPVM.

This research emphasizes the role that autoantibodies play in PEPVM. The fact that different autoantibodies appear to cause similar patterns demonstrates the heterogeneity of causes of vitelliform lesions.