Elsevier

Autoimmunity Reviews

Volume 6, Issue 3, January 2007, Pages 176-182
Autoimmunity Reviews

Alpha-enolase: A target of antibodies in infectious and autoimmune diseases

https://doi.org/10.1016/j.autrev.2006.10.004Get rights and content

Abstract

Alpha-enolase, also called non-neuronal enolase, belongs to a family of cytoplasmic and glycolytic enzymes. In addition to its glycolytic function, alpha-enolase exerts many other functions in eukaryotes and prokaryotes. Antibodies (Abs) against alpha-enolase have been detected in a large variety of infectious and autoimmune diseases. These Abs might arise as a consequence of a microbial infection or uncontrolled growth or proliferation of cells in specific organs in pathophysiological conditions. In infections, anti-alpha-enolase Abs could play a role in limiting microbial tissue invasion. In autoimmune and inflammatory diseases, anti-alpha-enolase Abs could induce endothelial injury through the generation of immune complexes and activation of the complement classical pathway, inhibit the binding of plasminogen to alpha-enolase with perturbations of the intravascular and pericellular fibrinolytic system, and induce cell death through an apoptotic process. However, further studies are needed to improve our knowledge on the pathogenic role of these Abs.

Introduction

Mammalian enolases constitute a family of cytoplasmic and glycolytic enzymes. Enolases family is composed of 3 isozyme subunits, alpha, beta and gamma, which can form homodimers or heterodimers and are cell-type and development-specific: alpha-enolase (also called non-neuronal enolase) is ubiquitous and expressed in the early stage of embryonic development, beta-enolase is expressed in adult skeletal and cardiac muscles, and gamma-enolase (also called neuron-specific enolase) is expressed in mature neuron and neuroendocrine tissues. Alpha-enolase catalyzes the dehydration of 2-phosphoglycerate to phosphoenolpyruvate. In addition to its glycolytic function, alpha-enolase performs many functions in eukaryotes and prokaryotes, and plays an important role in various pathophysiological processes [1]. Antibodies (Abs) against alpha-enolase have been detected in a large variety of infectious and autoimmune diseases. However, the reasons why the spectrum of associated-diseases is so wide and the pathogenic role of these auto-Abs remain unclear. We here propose to review the current knowledge on anti-alpha-enolase Abs in infectious and autoimmune diseases, with a specific focus on the potential pathophysiological role of these auto-Abs.

Section snippets

Alpha-enolase: structure, subcellular location and function

Alpha-enolase enzyme is composed of two subunits of 433 amino-acids, with a molecular weight of approximately 47 kDa each, for which magnesium is required for stabilizing the dimer. Despite the differences found in species, alpha-enolase is highly conserved, with a 40 to 90% identity between enolases from two different species [1]. Group A streptococcus and Saccharomyces cerevisiae enolases share 43% and 62% homology with human alpha-enolase, respectively. Analysis of the crystal structure of

Anti-alpha-enolase antibodies in infectious diseases

Antibodies against S. pneumoniae alpha-enolase develop early in life. Adrian et al., in a cohort study of children presenting with otitis media during their first two years of life, detected Abs against S. pneumoniae-alpha enolase in 99% of the sera [9]. The authors suggest the high prevalence of anti-alpha-enolase Abs in children to be due to cross-reactive epitopes of alpha-enolase from colonizing bacterial species because of the high degree of homology of alpha-enolase among these species [9]

Anti-alpha-enolase antibodies in systemic autoimmune disorders

Anti-alpha-enolase Abs have been found in a large variety of autoimmune and inflammatory diseases. Anti-alpha-enolase Abs have been initially reported in sera from patients that reacted with centrosomes in systemic rheumatic diseases [8]. Then, anti-alpha-enolase Abs have been shown to be a minor target antigen of anti-neutrophil cytoplasm Abs (ANCA) in systemic vasculitides [12], ulcerative colitis and Crohn's disease [13], and primary sclerosing cholangitis [14]. Since then,

Pathogenic role of anti-alpha-enolase antibodies

Anti-alpha-enolase Abs might be produced after a contact with bacteria or yeast and cross react with human-alpha-enolase [15]. Indeed, Fontan et al. suggested that Abs raised against streptococcal alpha-enolase during S. pyogenes infections might recognize common epitopes of human alpha-enolase expressed at the membrane of eukaryotic cells and could be involved in post streptococcal sequelae [4]. Interestingly, higher titers of anti-streptococcal alpha-enolase Abs are found in serum samples

Acknowledgements

This work is supported by grants from the Association des Sclérodermiques de France (ASF) and the Legs POIX, Chancellerie des Universités, Académie de Paris, France. Benjamin Terrier received a financial support from the Direction régionale des Affaires Sanitaires et Sociales. Philippe Guilpain is on a grant from the “Fondation pour la Recherche Médicale (FRM)”; Amélie Servettaz is on a grant from Actelion and the “Association des Sclérodermiques de France”. Amélie Servettaz and Luc Mouthon are

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