A Possible Link between Infection with Burkholderia Bacteria and Systemic Lupus Erythematosus Based on Epitope Mimicry

Wei Zhang,Morris Reichlin

doi:10.1155/2008/683489

Abstract

We previously demonstrated that purified polyclonal and monoclonal anti-dsDNA antibodies bind a 15-mer peptide ASPVTARVLWKASHV in ELISA and Dot blot. This 15-mer peptide partial sequence ARVLWKASH shares similarity with burkholderia bacterial cytochrome B 561 partial sequence ARVLWRATH. In this study, we show that purified anti-dsDNA antibodies react with burkholderia fungorum bacterial cell lysates in Western blot. We used anti-dsDNA antibodies to make an anti-dsDNA antibodies affinity column and used this column to purify the burkholderia fungorum bacterial protein. Purified anti-dsDNA antibodies bind specifically to purified bacterial antigen and purified bacterial antigen blocked the anti-dsDNA antibodies binding to dsDNA antigen. Sera with anti-dsDNA antibodies bind specifically to purified bacterial antigen. We obtained protein partial sequence of RAGTDEGFG which is shared with burkholderia bacterial transcription regulator protein sequence. Sera with anti-dsDNA antibodies bind to RAGTDEGFG peptide better than control groups. These data support our hypothesis that the origin of anti-dsDNA antibodies in SLE may be associated with burkholderia bacterial infection.

Highlights

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects multiple organ systems
We tested 12 purified anti-dsDNA antibodies from SLE patients and found that seven of these purified antibodies can bind the burkholderia fungorum bacterial protein in Western Blot (Figure 1)
We used one of the SLE patients anti-dsDNA antibodies that reacts with the burkholderia fungorum bacterial protein to make an anti-dsDNA antibody affinity column

Summary

Introduction

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects multiple organ systems. The etiology of SLE, and of autoimmunity in general remain unknown, considerable evidence has been accumulated on the pathophysiologic mechanisms, which lead to the failure of distinction between self and nonself and the production of autoantibodies. Antinuclear antibodies are a hallmark of SLE, whereas anti-dsDNA antibodies are a very specific marker for this disease. High-affinity anti-dsDNA antibodies correlate with disease activity, especially with renal involvement. Over the past several years, it has been clearly demonstrated that antidsDNA antibodies have pathogenic potential. Clinical data demonstrate that anti-dsDNA antibody titers correlate with disease activity in a significant number of patients with lupus nephritis, and glomerular eluates from patients with active lupus nephritis contain anti-dsDNA antibodies [1, 2]

Methods

Results

Conclusion