Dataset Information

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.

SUBMITTER: Goules A

PROVIDER: S-EPMC6857985 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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

Goules Andreas A Li Jessica J Antiochos Brendan B Goldman Daniel W DW Rosen Antony A Petri Michelle M Casciola-Rosen Livia L

ACR open rheumatology 20190606 5

<h4>Objective</h4>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.<h4>Methods</h4>Sera from 222 patients with SLE from the Hopkins longitudinal cohort were studied. Additional cohorts tested included ...[more]

PMID: 31777805

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Project description:OBJECTIVE:Immunoglobulin M antibodies against phosphorylcholine (anti-PCs) may be protective in atherosclerosis, cardiovascular disease (CVD), and systemic lupus erythematosus (SLE). We study immunoglobulin G1 (IgG1) and immunoglobulin G2 (IgG2) anti-PCs, with a focus on atherosclerosis and SLE. METHODS:We determined anti-PCs by using the enzyme-linked immunosorbent assay in 116 patients with SLE and 110 age- and sex-matched controls. For functional studies, we used three in-house-generated, fully human monoclonal IgG1 anti-PCs (A01, D05, and E01). Apoptosis was induced in Jurkat T cells and preincubated with A01, D05, E01, or IgG1 isotype control, and effects on efferocytosis by human macrophages were studied. Anti-PC peptide/protein characterization was determined using a proteomics de novo sequencing approach. RESULTS:IgG1, but not IgG2, anti-PC levels were higher among patients with SLE (P = 0.02). IgG1 anti-PCs were negatively associated with Systemic Lupus International Collaborating Clinics (SLICC) damage index and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores (odds ratio [OR]: 2.978 [confidence interval (CI): 0.876-10.098] and OR: 5.108 [CI 1.3-20.067], respectively) and negatively associated with CVD, atherosclerotic plaques, and echolucent plaques (potentially vulnerable plaques), but the association for the two former was not significant after controlling for confounders. D05 had a maximum effect on macrophage efferocytosis efficiency, followed by A01 and E01. The monoclonal antibodies showed differential binding specificity to PC and PC-associated neoepitopes. A peptide analysis showed a difference in the complementarity-determining region 3 of the three IgG1 anti-PC clones that are crucial for recognition of PC on apoptotic cell surfaces and other neoepitopes. CONCLUSION:IgG1 anti-PCs are negatively associated with disease activity and disease damage in SLE, but the negative association with CVD is also dependent on confounding risk factors. One potential underlying mechanism could be increased clearance of dead cells.

Dataset Information

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

Publications

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

Similar Datasets

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