title: Lymphoid aggregates that resemble tertiary lymphoid organs define a specific pathological subset in metal-on-metal hip replacements.
abstract: Aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL) has been used to describe the histological lesion associated with metal-on-metal (M-M) bearings. We tested the hypothesis that the lymphoid aggregates, associated with ALVAL lesions resemble tertiary lymphoid organs (TLOs). Histopathological changes were examined in the periprosthetic tissue of 62 M-M hip replacements requiring revision surgery, with particular emphasis on the characteristics and pattern of the lymphocytic infiltrate. Immunofluorescence and immunohistochemistry were used to study the classical features of TLOs in cases where large organized lymphoid follicles were present. Synchrotron X-ray fluorescence (XRF) measurements were undertaken to detect localisation of implant derived ions/particles within the samples. Based on type of lymphocytic infiltrates, three different categories were recognised; diffuse aggregates (51%), T cell aggregates (20%), and organised lymphoid aggregates (29%). Further investigation of tissues with organised lymphoid aggregates showed that these tissues recapitulate many of the features of TLOs with T cells and B cells organised into discrete areas, the presence of follicular dendritic cells, acquisition of high endothelial venule like phenotype by blood vessels, expression of lymphoid chemokines and the presence of plasma cells. Co-localisation of implant-derived metals with lymphoid aggregates was observed. These findings suggest that in addition to the well described general foreign body reaction mediated by macrophages and a T cell mediated type IV hypersensitivity response, an under-recognized immunological reaction to metal wear debris involving B cells and the formation of tertiary lymphoid organs occurs in a distinct subset of patients with M-M implants.
authors.affiliation: Rheumatology Research Group, Institute of Biomedical Research, MRC Centre for Immune Regulation, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Saloni
authors.initials: S
authors.lastname: Mittal
authors.forename: Matthew
authors.initials: M
authors.lastname: Revell
authors.forename: Francesca
authors.initials: F
authors.lastname: Barone
authors.forename: Debbie L
authors.initials: DL
authors.lastname: Hardie
authors.forename: Gulraj S
authors.initials: GS
authors.lastname: Matharu
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Davenport
authors.forename: Richard A
authors.initials: RA
authors.lastname: Martin
authors.forename: Melissa
authors.initials: M
authors.lastname: Grant
authors.forename: Frederick
authors.initials: F
authors.lastname: Mosselmans
authors.forename: Paul
authors.initials: P
authors.lastname: Pynsent
authors.forename: Vaiyapuri P
authors.initials: VP
authors.lastname: Sumathi
authors.forename: Owen
authors.initials: O
authors.lastname: Addison
authors.forename: Peter A
authors.initials: PA
authors.lastname: Revell
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Buckley
mesh_terms: D053264:B-Cell Activating Factor / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D002470:Cell Survival; D054421:Chemokine CCL21 / Q000378:metabolism; D054382:Chemokine CXCL13 / Q000378:metabolism; D042783:Endothelial Cells / Q000473:pathology; D006621:Hip Joint / Q000473:pathology* / Q000601:surgery; D006622:Hip Prosthesis; D006801:Humans; D007477:Ions; D008198:Lymph Nodes / Q000473:pathology*; D061825:Metal-on-Metal Joint Prostheses; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000378:metabolism; D014699:Venules / Q000473:pathology
chemical_list: D053264:B-Cell Activating Factor; D054421:Chemokine CCL21; D054382:Chemokine CXCL13; D007477:Ions; C505719:TNFSF13B protein, human; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13