• 2018-07
  • 2018-10
  • 2018-11
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • Obviously there are some limitations in our study


    Obviously, there are some limitations in our study; due to sample constraints, we had to focus our efforts on one specific T cell epitope from one candidate autoantigen. Optimally, we could have studied several different peptides in parallel. Additionally, all RA patients included in the study have a chronic disease, and all of them are immunosuppressed, which could affect the observed frequency and functionality of their T Phenyl sulfate and [13]. However, our cohort is representative for real life scenario patients. In fact, our data on peripheral blood are in good agreement with other studies using both in vitro and ex vivo approaches [13,48]. Our results using synovial fluid cells, furthermore, corroborate the findings from the borrelia-induced Lyme arthritis, showing higher frequency of antigen-(borrelia)-reactive T cells in synovial fluid compared to peripheral blood [49,50].
    Conclusions We identified and characterized autoreactive CD4+ T cells specific for HLA-DRB1*04:01 in complex with the RA autoantigen α-enolase-derived native eno326-340 and citrullinated cit-eno326-340 peptides in the periphery, synovial fluids and synovial tissues of RA patients. Importantly, citrulline-α-enolase-specific T cells were more often of a memory phenotype in the circulation and were enriched in the synovial fluid compared to those recognizing the native variant of the peptide. This study highlights the added value of interrogating the inflamed joint and not only peripheral blood when studying autoimmunity.
    Funding Work performed at KI was supported by grants from the Margaretha af Ugglas Foundation, the Swedish Association against Rheumatism, the Swedish Medical Association, the King Gustaf-V-80-year Foundation, the Swedish Research Council, Boehringer Ingelheim Fonds, Knut and Alice Wallenberg Foundation, the EU FP7-project Masterswitch (HEALTH-F2-2008-223404), Janssen Research and Development, and the IMI JU funded project BTCure 115142-2. Work performed at Uppsala was supported by the Swedish Research Council, Knut and Alice Wallenberg Foundation, and work at BRI was supported by NIAID 5U19 AI050864, NIMS 5 R01 AR037296, and NIAID UO1 AI101981.
    Introduction Lohman and Mayerho discovered enolase in muscle extracts when studying the conversion of 3-phosphoglyceric acid into pyruvic acid in 1934, Subsequent studies have shown that three types of enolase isoenzymes exist in mammals: α-enolase (ENO1) is present in almost all mature tissues; β-enolase (ENO3) exists primarily in muscle tissues; and γ-enolase (ENO2) occurs mainly in nervous and neuroendocrine tissues. All enolases are composed of two identical subunits. The molecular weights of enolases range from 82 to 100 ku. In humans and other mammals, 3 independent genetic loci (α, β and γ) encode the 3 enolase isozymes. However, another enolase that is different from ENO1, ENO2 and ENO3 has recently been discovered in human and mouse sperm. This newly discovered enolase, termed enolase 4 (ENO4), is related to sperm motility and male reproduction (Nakamura et al., 2013). The present article mainly reviews the basic characteristics and biological functions of ENO1.
    Basic characteristics of ENO1 Alpha-enolase, also known as 2-phospho-D-glycerate hydrolase, is a metalloenzyme that catalyzes the conversion of 2-phosphoglyceric acid to phosphoenolpyruvic acid in the glycolytic pathway. Petrak et al. (2008) statistically analyzed the frequency of the appearance of various terms related to human, rat and mouse proteins in the journal “Proteomics” (volumes from 4 to 6, from 2004 to 2006) and calculated the frequency of each term present in the database. It was found that ENO1 was a protein with an extremely high term frequency. Pancholi (2001) compared the amino acid sequences of ENO1 derived from 39 species. They found that although the amino acid sequences of ENO1 are different between species, ENO1 appears to be highly conserved. Alpha-enolase exhibits an overall amino acid sequence homology across species from 40% to 90% (Pancholi, 2001). Alpha-enolase proteins derived from various species are all composed of two structural domains: a smaller N-terminus and a larger C-terminus. The N-terminus shows a β3α4 topology, while the C-terminus shows an hββαα (βa) 6 topology.