Autoantibodies specific for alpha-enolase in systemic autoimmune disorders.

OBJECTIVE

To analyze the presence and specificity of anti-alpha-enolase antibodies in various systemic autoimmune diseases.

METHODS

Sera from patients with systemic lupus erythematosus (SLE), mixed cryoglobulinemia (MC), systemic sclerosis (SSc), and rheumatoid arthritis (RA) were tested by immunoblot on partially purified a-enolase from human kidney and on beta- and gamma-enolase. The isotype of anti-enolase antibodies was determined by means of isotype-specific monoclonal antibodies.

RESULTS

IgG anti-alpha-enolase antibodies were detected in 9/33 (27%) SLE sera (6/9 patients had active renal disease), in 6/19 sera from patients with MC and nephritis, in 0/15 sera from MC patients without renal involvement, in 6/20 (30%) SSc sera, in 2/35 (6%) disease controls with RA, and in 2/32 (6%) healthy controls. The antibodies were not species-specific, but in most cases were specific for the alpha isoform of enolase. The anti-enolase immune response was not isotypically restricted. In half of the patients with SLE the anti-alpha-enolase and anti-DNA antibodies constituted distinct antibody populations, while in the other half a partial overlap of the 2 antibody specificities was observed.

CONCLUSION

Anti-alpha-enolase antibodies can frequently be detected in systemic autoimmune disorders. In SLE and MC they are associated with nephritis and in SSc they are associated with severe endothelial damage. Alpha-enolase is ubiquitous, but is highly expressed in the kidney and also on the membrane of several cell types including endothelial cells. Thus, anti-alpha-enolase antibodies could contribute to renal injury not only by the local formation of immune complexes, but also by direct damage to endothelial cells.