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THU0505 Characterization of Phenotype and Immunoglobulin Genes of Autoreactive B Cells in SjÖGren's Syndrome
  1. P. Efthimiou1,2,
  2. S. Kadavath1,
  3. A. Bhatta3,
  4. E. Charles4,
  5. L. Dustin5
  1. 1Rheumatology, Lincoln Medical and Mental Health Center
  2. 2Weill Cornell Medical College
  3. 3Rockerfeller University
  4. 4Merck, NY, United States
  5. 5Professor of Immunology and Virology, Kennedy Institute of Rheumatology, University of Oxford, United Kingdom, United Kingdom

Abstract

Background Characteristic changes in the distribution of peripheral B cell subsets and differences in use of immunoglobulin-variable region genes are features of Sjögren's Syndrome (SS). Studies on Hepatitis C virus infected (HCV+) mixed Cryoglobulinemia (MC) patients have revealed B cell clonal expansion expressing stereotypical Rheumatoid Factor (RF) encoded by the immunoglobulin genes VH1-69 and Vk 3-20. G6 antibody specific for VH1-69 can identify the RF- expressing B cells in HCV+MC patients.Since some SS patients have been known to develop lymphomas bearing VH1-69 encoded antibodies, we hypothesized that SS patients might have clonal expansions of VH1-69-bearing B cells.

Objectives Identify B lymphocyte characteristics in patients with Sjogren's syndrome

Methods We obtained blood samples from 13 patients diagnosed with SS at a teaching hospital rheumatology clinic, serving a large inner city population. Further processing of the blood samples from these patients was done at Rockefeller University and the Peripheral Blood Mononuclear Cells (PBMCs) were cryopreserved. Fluorescent- labeled Ro/SS-A (52,60kDA) and La-SS-B antigens were obtained. The purpose was to label B cells that make SS-A antibody so they could be seen by flow cytometry.

Results Preliminary flow cytometric analysis of B cells in 8 of the blood samples showed a B cell phenotype different from that seen in HCV-associated MC. The memory B cells were high in CD-21, unlike those seen in HCV-associated MC. Few VH1-69 + B cells were seen in 4/8 patients analyzed. The other blood samples showed very few cells binding SS-A.

Conclusions Unraveling the association between autoimmunity and lympoproliferation in SS patients will have clinical value, and B cell gene expression data may be able to predict susceptibility to lymphoma in these individuals. The abnormally expanded B cells should be studied at the transcriptional, proteomic and functional levels. The lack of direct comparison between the B cell repertoire in the blood and that in the parotids and/or minor salivary glands has prevented drawing of firm conclusions. The long term goal would be to clone, sequence and characterize autoantibodies produced in SS.

Disclosure of Interest : None declared

DOI 10.1136/annrheumdis-2014-eular.5796

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