title: Autoantibodies to post-translationally modified type I and II collagen in Charcot neuroarthropathy in subjects with type 2 diabetes mellitus.
abstract: Charcot neuroarthropathy (CN) is a disabling complication, culminating in bone destruction and involving joints and articular cartilage with high inflammatory environment. Its real pathogenesis is as yet unknown. In autoinflammatory diseases, such as rheumatoid arthritis, characterized by inflammation and joint involvement, autoantibodies against oxidative post-translationally modified (oxPTM) collagen type I (CI) and type II (CII) were detected. Therefore, the aim of our study was to assess the potential involvement of autoimmunity in charcot neuroarthropathy, investigating the presence of autoantibodies oxPTM-CI and oxPTM-CII, in participants with charcot neuroarthropathy.
  
  
  
  In this case-control study, we enrolled 124 participants with type 2 diabetes mellitus (47 with charcot neuroarthropathy, 37 with diabetic peripheral neuropathy without charcot neuroarthropathy, and 40 with uncomplicated diabetes), and 32 healthy controls. The CI and CII were modified with ribose and other oxidant species, and the modifications were evaluated with sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Binding of sera from the participants was analyzed with enzyme-linked immunosorbent assay.
  
  
  
  Age, body mass index, waist and hip circumferences, and lipid profile were similar across the 4 groups, as well as glycated hemoglobin and duration of diabetes among people with diabetes. An increased binding to both native and all oxidation-modified forms of CII was found in participants with CN and diabetic neuropathy. Conversely, for CI, an aspecific increased reactivity was noted.
  
  
  
  Our results detected the presence of autoantibodies against oxidative post-translational modified collagen, particularly type 2 collagen, in participants with charcot neuroarthropathy and diabetic neuropathy, suggesting the possible involvement of autoimmunity. Further studies are required to understand the role of autoimmunity in the pathogenesis of charcot neuroarthropathy.
authors.affiliation: Diabetes Care Unit, Internal Medicine, University Hospital "A. Gemelli", Catholic University of the Sacred Heart, Rome, Italy.|Centre for Biochemical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, UK.
authors.forename: Paola
authors.initials: P
authors.lastname: Rizzo
authors.affiliation: Diabetes Care Unit, Internal Medicine, University Hospital "A. Gemelli", Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Pitocco
authors.affiliation: Diabetes Care Unit, Internal Medicine, University Hospital "A. Gemelli", Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Zaccardi
authors.affiliation: Institute of Biochemistry, University Hospital "A. Gemelli", Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Di Stasio
authors.affiliation: Centre for Biochemical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, UK.|Department of Endocrinology & Diabetes, Campus Bio-Medico, University of Rome, Rome, Italy.
authors.forename: Rocky
authors.initials: R
authors.lastname: Strollo
authors.affiliation: Diabetes Care Unit, Internal Medicine, University Hospital "A. Gemelli", Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Rizzi
authors.affiliation: Diabetes Care Unit, Internal Medicine, University Hospital "A. Gemelli", Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Scavone
authors.affiliation: Diabetes Care Unit, Internal Medicine, University Hospital "A. Gemelli", Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Costantini
authors.affiliation: Institute of Orthopedic Surgery, University Hospital "A. Gemelli", Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Galli
authors.affiliation: Department of Vascular Surgery, University Hospital "A. Gemelli", Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tinelli
authors.affiliation: Institute of Internal Medicine, University Hospital "A. Gemelli", Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Flex
authors.affiliation: Diabetes Care Unit, Internal Medicine, University Hospital "A. Gemelli", Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Caputo
authors.affiliation: Department of Endocrinology & Diabetes, Campus Bio-Medico, University of Rome, Rome, Italy.|Centre for Diabetes, Queen Mary University of London, London, UK.
authors.forename: Paolo
authors.initials: P
authors.lastname: Pozzilli
authors.affiliation: Institute of Internal Medicine, University Hospital "A. Gemelli", Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Landolfi
authors.affiliation: Diabetes Care Unit, Internal Medicine, University Hospital "A. Gemelli", Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ghirlanda
authors.affiliation: Centre for Biochemical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, UK.
authors.forename: Ahuva
authors.initials: A
authors.lastname: Nissim
mesh_terms: D000368:Aged; D001177:Arthropathy, Neurogenic / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D015415:Biomarkers / Q000097:blood*; D016022:Case-Control Studies; D024042:Collagen Type I / Q000276:immunology*; D024043:Collagen Type II / Q000276:immunology*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003929:Diabetic Neuropathies / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011499:Protein Processing, Post-Translational
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D024042:Collagen Type I; D024043:Collagen Type II
keywords: Charcot neuroarthropathy; autoimmunity; diabetic foot; oxidative stress