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Abstract Number: 726

Anti-Retinoblastoma Protein Antibody Is Protective Against Lupus Nephritis

Jessica Li1, Andreas Goules2, Daniel Goldman1, Antony Rosen3, Livia Casciola-Rosen4 and Michelle Petri1, 1Medicine (Rheumatology), Johns Hopkins University School of Medicine, Baltimore, MD, 2Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, 3Division of Rheumatology, The Johns Hopkins University School of Medicine, Baltimore, MD, 4Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD

Meeting: ACR/ARHP Annual Meeting 2018

Keywords: ,

Session Information

Date: Sunday, October 21, 2018

Title: Systemic Lupus Erythematosus – Clinical Poster I: Clinical Manifestations and Comorbidity

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: Retinoblastoma protein (RB) regulates nucleosome/chromatin structures and is linked to tumor suppression. It regulates the cell cycle by repression of E2F transcription factor and stabilization of heterochromatin. Because SLE is the prototypic autoimmune disease with autoantibodies against the nucleosome and chromatin, the presence of anti-RB antibodies and the association with disease manifestations were examined.

Methods: 222 SLE patients from the Hopkins longitudinal cohort seen consecutively in clinic were studied (85% female, 94% Caucasian, mean age 51 years). Anti-RB antibodies were assayed by immunoprecipitation of 35S-methionine-labeled protein generated by in vitro transcription and translation from full length human cDNA. Odds ratios and p-values for univariate analyses were calculated using Fisher’s exact t-test. Exact logistic regression and odds ratios were calculated for the multi-variate model due to a cell frequency of zero for proteinuria ever and positive anti-RB antibody status.

Results: Anti-RB antibodies were present in 8.6% of these SLE patients, 6.3% with medium-high titer. Univariate associations with SLE manifestations for the medium-high titer positive patients are included in Table 1.

Table 1. Association of Anti-RB antibodies with SLE Manifestations

Anti-Rb Positive (N=14)

Anti-Rb Negative (N=203)

p-value

OR (95% CI)

Vasculitis ever

0 (0.0%)

34 (16.8%)

0.1338

N/C

Proteinuria ever

0 (0.0%)

75 (37.0%)

0.0028

N/C

Hematuria ever

1 (7.1%)

43 (21.2%)

0.3103

0.29 (0.04, 2.25)

Renal SLE ever
(Hematuria OR Proteinuria)

1 (7.1%)

81 (39.9%)

0.0145

0.12 (0.01, 0.9)

Stroke ever

2 (14.3%)

3(1.5%)

0.0347

11.11 (1.69, 72.94)

Anemia ever

1 (7.1%)

124 (61.1%)

<0.0001

0.05 (0.01, 0.38)

Anti-Ro

4 (28.6%)

65 (32.2%)

1.0000

0.84 (0.25, 2.79)

Anti-La

1 (7.1%)

31 (15.4%)

0.6988

0.42 (0.05, 3.36)

Anti-RNP

1 (7.1%)

36 (17.7%)

0.4731

0.36 (0.05, 2.82)

Anti-Smith

1 (7.1%)

35 (17.2%)

0.4745

0.37 (0.05, 2.92)

Anti-dsDNA

6 (42.9%)

126 (62.1%)

0.1679

0.46 (0.15, 1.37)

RVVT

2 (14.3%)

69 (34.0%)

0.1525

0.32 (0.07, 1.49)

Anticardiolipin

9 (64.3%)

124 (61.1%)

1.0000

1.15 (0.37, 3.55)

Coombs

1 (7.1%)

33 (16.3%)

0.7021

0.40 (0.05, 3.13)

N/C=odds ratio was not calculated due to zero cell frequencies

Of note, medium/high titer anti-RB antibodies were never found in patients with proteinuria (p=0.0028). We next constructed a multi-variate model for proteinuria.

Table 2. Anti-RB antibodies Remain Negatively associated in a Multi-variate Model for Proteinuria

Variables

OR (95% CI)

p-value

Anti-RB

0.112 (0, 0.558)

0.016

Gender (Female)

0.417 (0.172, 0.999)

0.0498

Ethnicity (Caucasian)

0.288 (0.06, 1.144)

0.0833

Anti-dsDNA

1.806 (0.873, 3.808)

0.1192

Anti-Sm

1.273 (0.505, 3.154)

0.7127

Low complement

2.111 (1.04, 4.377)

0.0377

Conclusion: Anti-RB antibodies are a novel specificity not previously described in SLE. These antibodies are strongly negatively associated with lupus nephritis, even in multivariate models that include other variables (female gender, Caucasian ethnicity, anti-dsDNA, anti-Sm, and low complement). Intriguingly, anti-RB antibodies are positively associated with stroke in SLE. Additional studies are warranted to understand the mechanism of this finding.

Disclosure: J. Li, None; A. Goules, None; D. Goldman, Merck & Co., Pfizer, 1; A. Rosen, None; L. Casciola-Rosen, None; M. Petri, EMD Serono, 5,Exagen, 2,Janssen, 5,GSK, 5,AstraZeneca, 2,Inova Diagnostic, 5,Novartis, 5,Amgen Inc., 5,Decision Resources, 5,Medscape, 5,Eli Lilly and Co., 5,Quintiles, 5.

To cite this abstract in AMA style:

Li J, Goules A, Goldman D, Rosen A, Casciola-Rosen L, Petri M. Anti-Retinoblastoma Protein Antibody Is Protective Against Lupus Nephritis [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/anti-retinoblastoma-protein-antibody-is-protective-against-lupus-nephritis/. Accessed .

ACR Meeting Abstracts - https://acrabstracts.org/abstract/anti-retinoblastoma-protein-antibody-is-protective-against-lupus-nephritis/