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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.

Type

Journal article

Journal

PloS one

Publication Date

01/2013

Volume

8

Addresses

Rheumatology Research Group, Institute of Biomedical Research, MRC Centre for Immune Regulation, University of Birmingham, Birmingham, United Kingdom.

Keywords

Hip Joint, Venules, Lymph Nodes, B-Lymphocytes, T-Lymphocytes, Endothelial Cells, Humans, Ions, Hip Prosthesis, Cell Proliferation, Cell Survival, B-Cell Activating Factor, Tumor Necrosis Factor Ligand Superfamily Member 13, Chemokine CXCL13, Chemokine CCL21, Metal-on-Metal Joint Prostheses