Anti‐retinoblastoma Protein Antibodies: A New Specificity in Systemic Lupus Erythematosus Associated With Protection Against Lupus Nephritis

Abstract

Objective Retinoblastoma (Rb) protein is a nuclear protein with several important functions, including the ability to stabilize heterochromatin. Because antibodies against the nucleosome and chromatin are key in systemic lupus erythematosus (SLE), we sought to determine whether Rb was an autoantigen in SLE and to evaluate any associated clinical phenotypes. Methods Sera from 222 patients with SLE from the Hopkins longitudinal cohort were studied. Additional cohorts tested included sera from 100 patients with primary Sjögren syndrome (pSS) (disease controls) evaluated at the Johns Hopkins Jerome L. Greene Sjögren's Center and sera from 36 healthy individuals. Anti‐Rb antibodies were assayed by immunoprecipitation of 35S‐methionine–labeled Rb, which was generated by in vitro transcription/translation. Fisher's exact test was used for the univariate analysis. Multivariable exact logistic regression was used to model for the presence of proteinuria in patients with SLE. Results Anti‐Rb antibodies were present in 15 of 222 (6.8%) patients with SLE, in 3 of 100 patients with pSS (3%), and in 0 of 36 healthy individuals. Among patients with SLE, Rb antibodies were strongly negatively associated with proteinuria (P = 0.0031), renal involvement (odds ratio [OR] = 0.11; P = 0.01), and anemia (OR = 0.05; P < 0.0001) and were positively associated with stroke (OR = 7.65; P = 0.05). The negative association with lupus nephritis held true in multivariate models (adjusted OR = 0.11; P = 0.01). Conclusion Anti‐Rb antibodies are a novel specificity not previously described in SLE. These new data define a possible SLE subset that is protected against renal involvement, is positively associated with stroke, and is not associated with antiphospholipid antibodies.