Alpha-enolase: A target of antibodies in infectious and autoimmune diseases
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.
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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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2021, Experimental Eye ResearchCitation Excerpt :Observation of the decreases in these enzyme levels in the PVR model appears to be consistent with retinal damage and inflammation reported in the literature. ENO1 activity is decreased in cancer-associated retinopathy, autoimmune retinopathy and inflammatory diseases due to the production of this protein (Adamus, 2017; Adamus et al., 1998; Magrys et al., 2007; Terrier et al., 2007). ENO2 levels is shown to decrease in RD, PVR, and DRP (Ducournau et al., 2012; Wang et al., 2012, 2013).