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      Increased expression of inducible co-stimulator on CD4+ T-cells in the peripheral blood and synovial fluid of patients with failed hip arthroplasties

      research-article
      Author(s): , PhD, FRCPath, FBSE 1 , , , BSc (Hons), MRCS, MRes 1 , , PhD 2 , , PhD 1 , , DPhil, FRCP 2 , , BSc, MBA, FRCS (Tr&Orth) 1
      Publication date (Electronic):
      Journal: Bone & Joint Research
      Keywords: hip arthroplasty, metal-on-metal, metal-on-polyethylene, failure, T-cell activation, co-stimulatory molecules

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          Abstract

          Objectives

          T-cells are considered to play an important role in the inflammatory response causing arthroplasty failure. The study objectives were to investigate the composition and distribution of CD4+ T-cell phenotypes in the peripheral blood (PB) and synovial fluid (SF) of patients undergoing revision surgery for failed metal-on-metal (MoM) and metal-on-polyethylene (MoP) hip arthroplasties, and in patients awaiting total hip arthroplasty.

          Methods

          In this prospective case-control study, PB and SF were obtained from 22 patients (23 hips) undergoing revision of MoM (n = 14) and MoP (n = 9) hip arthroplasties, with eight controls provided from primary hip osteoarthritis cases awaiting arthroplasty. Lymphocyte subtypes in samples were analysed using flow cytometry.

          Results

          The percentages of CD4+ T-cell subtypes in PB were not different between groups. The CD4+ T-cells in the SF of MoM hips showed a completely different distribution of phenotypes compared with that found in the PB in the same patients, including significantly decreased CD4+ T-central memory cells (p < 0.05) and increased T-effector memory cells (p < 0.0001) in the SF. Inducible co-stimulator (ICOS) was the only co-stimulatory molecule with different expression on CD4+ CD28+ cells between groups. In PB, ICOS expression was increased in MoM (p < 0.001) and MoP (p < 0.05) cases compared with the controls. In SF, ICOS expression was increased in MoM hips compared with MoP hips (p < 0.05).

          Conclusions

          Increased expression of ICOS on CD4+ T-cells in PB and SF of patients with failed arthroplasties suggests that these cells are activated and involved in generating immune responses. Variations in ICOS expression between MoM and MoP hips may indicate different modes of arthroplasty failure.

          Cite this article: Professor P. A. Revell. Increased expression of inducible co-stimulator on CD4+ T-cells in the peripheral blood and synovial fluid of patients with failed hip arthroplasties. Bone Joint Res 2016;5:52–60. DOI: 10.1302/2046-3758.52.2000574

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          Necrotic and inflammatory changes in metal-on-metal resurfacing hip arthroplasties

          Gayana Mahendra, Hemant Pandit, Karolina Kliskey … (2009)
          Background Necrosis and inflammation in peri-implant soft tissues have been described in failed second-generation metal-on-metal (MoM) resurfacing hip arthroplasties and in the pseudotumors associated with these implants. The precise frequency and significance of these tissue changes is unknown. Method We analyzed morphological and immunophenotypic changes in the periprosthetic soft tissues and femoral heads of 52 revised MoM arthroplasties (fracture in 21, pseudotumor in 13, component loosening in 9, and other causes in 9 cases). Results Substantial necrosis was observed in the periprosthetic connective tissue in 28 of the cases, including all pseudotumors, and 5 cases of component loosening. A heavy, diffuse inflammatory cell infiltrate composed mainly of HLA-DR+/CD14+/CD68+ macrophages and CD3+ T cells was seen in 45 of the cases. Perivascular lymphoid aggregates composed of CD3+ cells and CD20+ B cells were noted in 27 of the cases, but they were not seen in all cases of component loosening or pseudotumors. Plasma cells were noted in 30 cases. Macrophage granulomas were noted in 6 cases of component loosening. In the bone marrow of the femoral head, a macrophage and T cell response was seen in 31 of the cases; lymphoid aggregates were noted in 19 of the cases and discrete granulomas in 1 case. Interpretation Our findings indicate that there is a spectrum of necrotic and inflammatory changes in response to the deposition of cobalt-chrome (Co-Cr) wear particles in periprosthetic tissues. Areas of extensive coagulative necrosis and a macrophage and T lymphocyte response occur in implant failure and pseudotumors, in which there is also granuloma formation. The pathogenesis of these changes is uncertain but it may involve both a cytotoxic response and a delayed hypersensitivity (type IV) response to Co-Cr particles.
          Article 0 comments Cited 72 times – based on 0 reviews     Review now
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            Adverse reactions to metal debris: histopathological features of periprosthetic soft tissue reactions seen in association with failed metal on metal hip arthroplasties.

            Antoni V F Nargol, S. M. Natu, Raghavendra P Sidaginamale … (2012)
            To describe the histopathology of localised adverse reactions to metal debris (ARMD) seen in association with failed metal on metal (MoM) hip arthroplasties. The nature of aseptic lymphocytic vasculitis associated lesion (ALVAL) is investigated. Periprosthetic soft tissues biopsied at time of revision from failed MoM hip arthroplasties from January 2007 to March 2011 were analysed. The inflammatory cell response was categorised into perivascular lymphocytic cuffing (ALVAL), lymphoid aggregate formation with or without germinal centres, metallosis characterised by sheets of macrophages with intracytoplasmic metallic debris and well-defined granulomas. 123 patient samples were analysed, 36 males (29.2%) and 87 females (70.8%). Three cases showing complete tissue necrosis were excluded. Patients were reviewed between 3.27 to 69.6 months postarthroplasty, with an average of 30.92 months. 103 cases (85.8%) showed ALVAL, 18 cases also showed well-defined granulomas. Of the 103 cases with ALVAL, 60 cases also showed a diffuse chronic lymphocytic synovitis, and 40 cases showed lymphoid aggregates with germinal centres. 17 cases (14.2%) showed pure metallosis. Small vessels showing ALVAL expressed peripheral node addressin. ARMD is a spectrum of changes comprising of pure metallosis, ALVAL and granulomatous inflammation. ALVAL, a distinctive inflammatory response seen in ARMD, is a precursor of lymphoid neogenesis. Lymphoid neogenesis documented in a variety of chronic inflammatory conditions most probably contributes to tissue necrosis and prosthetic failure seen in MoM hip arthroplasties. The role of vascular changes in contributing to necrosis is unclear at this stage.
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              High complication rate after revision of large-head metal-on-metal total hip arthroplasty.

              Jacob Munro, Bassam Masri, Clive Duncan … (2014)
              Previous studies have indicated poor outcomes in patients having revision of hip resurfacing resulting from adverse local tissue reaction and pseudotumor.
              Article 0 comments Cited 33 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                P. A. Revell: Role: Emeritus Professor (UCL, London); Honorary Consultant (ROH, Birmingham)
                G. S. Matharu: Role: Specialist Registrar in Trauma and Orthopaedics
                S. Mittal: Role: Post-Doctoral Researcher, MRC Centre for Immune Regulation
                P. B. Pynsent: Role: Director of Research and Teaching
                C. D. Buckley: Role: Arthritis Research UK Professor of Rheumatology, Rheumatology Research Group, Institute of Biomedical Research and MRC Centre for Immune Regulation
                M. P. Revell: Role: Consultant Orthopaedic Surgeon
                Journal
                Journal ID (nlm-ta): Bone Joint Res
                Title: Bone & Joint Research
                ISSN (Electronic): 2046-3758
                Publication date Collection: February 2016
                Publication date (Electronic): 8 April 2016
                Volume: 5
                Issue: 2
                Pages: 52-60
                Affiliations
                [1 ]The Royal Orthopaedic Hospital NHS Foundation Trust, Bristol Road South, Birmingham B31 2AP, UK
                [2 ]University of Birmingham, Edgbaston, Birmingham B15 2WD, UK
                Author notes
                [*]Professor P. A. Revell; email: parevell@ 123456hotmail.co.uk
                Article
                Publisher ID: 10.1302_2046-3758.52.2000574
                DOI: 10.1302/2046-3758.52.2000574
                PMC ID: 4852791
                PubMed ID: 26868893
                SO-VID: 5e23b38c-b3a9-462b-affc-41578098b0b6
                Copyright © © 2016 Revell et al.
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attributions licence (CC-BY-NC), which permits unrestricted use, distribution, and reproduction in any medium, but not for commercial gain, provided the original author and source are credited.

                History
                Date received : 10 September 2015
                Date accepted : 9 December 2015
                Categories
                Subject: Hip
                Subject: 1
                Subject: Hip Arthroplasty
                Subject: Metal-on-Metal
                Subject: Metal-on-Polyethylene
                Subject: Failure
                Subject: T-Cell Activation
                Subject: Co-Stimulatory Molecules

                Keywords: hip arthroplasty,metal-on-metal,metal-on-polyethylene,failure,t-cell activation,co-stimulatory molecules
                Data availability:
                Keywords: hip arthroplasty, metal-on-metal, metal-on-polyethylene, failure, t-cell activation, co-stimulatory molecules

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