ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1953

Circulating Plasmablasts from Patients with Systemic Lupus Erythematosus Produce Autoantibodies Reactive to Epstein-Barr Virus

Yangsheng Yu1, Song Li1, Run Fan2, Yinshi Yue1, Hongyan Liao1, Zhixin Wang1, Lin Huang1, Qin Wang3, Michelene Hearth-Holmes4, Amy Cannella5, W. Winn Chatham6, Robert Kimberly2,7, James O'Dell8, Lynell Klassen5, Robert Carter7, Zhixin Zhang9,10 and Kaihong Su1,5,10, 1Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, 2Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, 3Shanghai Fengxian District Central Hospital, Shanghai Jiao Tong University, Shanghai, China, 4Internal Medicine/Rheumatology Division, University of Nebraska Medical Center, Omaha, NE, 5Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, 6University of Alabama at Birmingham, Birmingham, AL, 7Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, 8University of Nebraska Medical Center, Omaha, NE, 9Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, 10Eppley Cancer Institute, University of Nebraska Medical Center, Omaha, NE

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: ,

Session Information

Title: B cell Biology and Targets in Autoimmune Disease: Systemic Lupus Erythematosus and Related Diseases

Session Type: Abstract Submissions (ACR)

Background/Purpose:

Systemic lupus erythematosus (SLE) is characterized by the over-production of high affinity autoantibodies. It is not clear how such autoantibodies are generated during the course of lupus. The purpose of this study was to analyze the antibody repertoire in circulating plasmablasts in adult SLE patients and explore the molecular basis for the generation of such antibodies in SLE.

Methods:

Eight patients with active SLE and seven healthy controls were recruited for the study. Recombinant antibodies were cloned from circulating plasmablasts by single cell RT-PCR analyses. Auto and poly-reactivities of these antibodies were measured by indirect immunofluorescent anti-nuclear antibody assays (IFA-ANA) and ELISAs using a panel of antigens (dsDNA, ssDNA, insulin, and LPS) respectively. Anti-Epstein-Barr Virus (EBV) reactivity of antibodies was examined by ELISAs using EBV viral capsid antigen (VCA) as capturing antigens. 

Results:

In patients with active SLE, the relative frequencies of circulating plasmablasts were significantly increased compared to those of healthy controls (10.6% vs 1.0%, p=0.0013, n=8). Circulating plasmablasts from SLE patients, but not healthy controls, predominantly produced auto/polyreactive antibodies (autoreactive: 24.8% vs 4%, p<0.0001, n=8; polyreactive: 58.5% vs 11.3%, p<0.0001, n=8). Sequence analyses revealed excessive receptor editing and enrichment of VH replacement products in immunoglobulin (Ig) genes derived from SLE patients (20.6% vs 7.9%, p=0.0012, n=8). Interestingly, 76.7% of the VH replacement products derived from plasmablasts of SLE patients encoded auto/polyreactive antibodies. Furthermore, about 20% of circulating plasmablast-derived antibodies from SLE patients reacted with EBV VCA antigens. These SLE-derived anti-EBV antibodies cross-reacted with dsDNA and other nuclear antigens. VH replacement products were also significantly enriched in Ig heavy chain genes encoding anti-EBV antibodies.

Conclusion:

The elevated frequencies of auto/polyreactive antibodies, enrichment of VH replacement products, and production of anti-EBV-VCA antibodies in plasmablasts from SLE patients indicate that autoreactive B cells in active SLE patients are positively selected by EBV antigens. This finding supports the hypothesis that preventing EBV infection is a beneficial intervention to limit active disease in SLE patients.

Disclosure:

Y. Yu,
None;

S. Li,
None;

R. Fan,
None;

Y. Yue,
None;

H. Liao,
None;

Z. Wang,
None;

L. Huang,
None;

Q. Wang,
None;

M. Hearth-Holmes,
None;

A. Cannella,
None;

W. W. Chatham,
None;

R. Kimberly,
None;

J. O’Dell,

Abbvie, Lilly, Antares, Medac,

5;

L. Klassen,
None;

R. Carter,
None;

Z. Zhang,
None;

K. Su,
None.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/circulating-plasmablasts-from-patients-with-systemic-lupus-erythematosus-produce-autoantibodies-reactive-to-epstein-barr-virus/