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Autoantibodies to post-translationally modified type I and II collagen in Charcot neuroarthropathy in subjects with type 2 diabetes mellitus.
Diabetes Metab Res Rev. 2017 02; 33(2)DM

Abstract

AIMS

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

Links

Publisher Full Text (DOI)

Authors+Show Affiliations

Rizzo P
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.
Pitocco D
Diabetes Care Unit, Internal Medicine, University Hospital "A. Gemelli", Catholic University of the Sacred Heart, Rome, Italy.
Zaccardi F
Diabetes Care Unit, Internal Medicine, University Hospital "A. Gemelli", Catholic University of the Sacred Heart, Rome, Italy.
Di Stasio E
Institute of Biochemistry, University Hospital "A. Gemelli", Catholic University of the Sacred Heart, Rome, Italy.
Strollo R
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.
Rizzi A
Diabetes Care Unit, Internal Medicine, University Hospital "A. Gemelli", Catholic University of the Sacred Heart, Rome, Italy.
Scavone G
Diabetes Care Unit, Internal Medicine, University Hospital "A. Gemelli", Catholic University of the Sacred Heart, Rome, Italy.
Costantini F
Diabetes Care Unit, Internal Medicine, University Hospital "A. Gemelli", Catholic University of the Sacred Heart, Rome, Italy.
Galli M
Institute of Orthopedic Surgery, University Hospital "A. Gemelli", Catholic University of the Sacred Heart, Rome, Italy.
Tinelli G
Department of Vascular Surgery, University Hospital "A. Gemelli", Catholic University of the Sacred Heart, Rome, Italy.
Flex A
Institute of Internal Medicine, University Hospital "A. Gemelli", Catholic University of the Sacred Heart, Rome, Italy.
Caputo S
Diabetes Care Unit, Internal Medicine, University Hospital "A. Gemelli", Catholic University of the Sacred Heart, Rome, Italy.
Pozzilli P
Department of Endocrinology & Diabetes, Campus Bio-Medico, University of Rome, Rome, Italy. Centre for Diabetes, Queen Mary University of London, London, UK.
Landolfi R
Institute of Internal Medicine, University Hospital "A. Gemelli", Catholic University of the Sacred Heart, Rome, Italy.
Ghirlanda G
Diabetes Care Unit, Internal Medicine, University Hospital "A. Gemelli", Catholic University of the Sacred Heart, Rome, Italy.
Nissim A
Centre for Biochemical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, UK.

MeSH

AgedArthropathy, NeurogenicAutoantibodiesBiomarkersCase-Control StudiesCollagen Type ICollagen Type IIDiabetes Mellitus, Type 2Diabetic NeuropathiesEnzyme-Linked Immunosorbent AssayFemaleFollow-Up StudiesHumansMaleMiddle AgedPrognosisProtein Processing, Post-Translational

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

27454862

Citation

Rizzo, Paola, et al. "Autoantibodies to Post-translationally Modified Type I and II Collagen in Charcot Neuroarthropathy in Subjects With Type 2 Diabetes Mellitus." Diabetes/metabolism Research and Reviews, vol. 33, no. 2, 2017.
Rizzo P, Pitocco D, Zaccardi F, et al. Autoantibodies to post-translationally modified type I and II collagen in Charcot neuroarthropathy in subjects with type 2 diabetes mellitus. Diabetes Metab Res Rev. 2017;33(2).
Rizzo, P., Pitocco, D., Zaccardi, F., Di Stasio, E., Strollo, R., Rizzi, A., Scavone, G., Costantini, F., Galli, M., Tinelli, G., Flex, A., Caputo, S., Pozzilli, P., Landolfi, R., Ghirlanda, G., & Nissim, A. (2017). Autoantibodies to post-translationally modified type I and II collagen in Charcot neuroarthropathy in subjects with type 2 diabetes mellitus. Diabetes/metabolism Research and Reviews, 33(2). https://doi.org/10.1002/dmrr.2839
Rizzo P, et al. Autoantibodies to Post-translationally Modified Type I and II Collagen in Charcot Neuroarthropathy in Subjects With Type 2 Diabetes Mellitus. Diabetes Metab Res Rev. 2017;33(2) PubMed PMID: 27454862.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Autoantibodies to post-translationally modified type I and II collagen in Charcot neuroarthropathy in subjects with type 2 diabetes mellitus. AU - Rizzo,Paola, AU - Pitocco,Dario, AU - Zaccardi,Francesco, AU - Di Stasio,Enrico, AU - Strollo,Rocky, AU - Rizzi,Alessandro, AU - Scavone,Giuseppe, AU - Costantini,Federica, AU - Galli,Marco, AU - Tinelli,Giovanni, AU - Flex,Andrea, AU - Caputo,Salvatore, AU - Pozzilli,Paolo, AU - Landolfi,Raffaele, AU - Ghirlanda,Giovanni, AU - Nissim,Ahuva, Y1 - 2016/10/05/ PY - 2016/01/19/received PY - 2016/07/05/revised PY - 2016/07/18/accepted PY - 2016/7/28/pubmed PY - 2017/9/28/medline PY - 2016/7/26/entrez KW - Charcot neuroarthropathy KW - autoimmunity KW - diabetic foot KW - oxidative stress JF - Diabetes/metabolism research and reviews JO - Diabetes Metab Res Rev VL - 33 IS - 2 N2 - AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. SN - 1520-7560 UR - https://www.unboundmedicine.com/medline/citation/27454862/Autoantibodies_to_post_translationally_modified_type_I_and_II_collagen_in_Charcot_neuroarthropathy_in_subjects_with_type_2_diabetes_mellitus_ DB - PRIME DP - Unbound Medicine ER -