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While MoM and MoP ALTRs are presumed to be delayed hypersensitivity reactions to corrosion products, MoM\u2010 and MoP\u2010associated ALTRs present with different histological characteristics. We compared MoM\u2010 and MoP\u2010associated ALTRs histopathology with cobalt and chromium levels in serum and synovial fluid. We analyzed the gene expression levels of leukocyte aggregates and synovial fluid chemokines\/cytokines to resolve potential pathophysiologic differences. In addition, we classified ALTRs from 79 patients according to their leukocyte infiltrates as macrophage\u2010dominant, mixed, and lymphocyte\u2010dominant. Immune\u2010related transcript profiles from lymphocyte\u2010dominant MoM\u2010 and MoP\u2010associated ALTR\u00a0patients with perivascular lymphocytic aggregates were similar. Cell signatures indicated predominantly macrophage, Th1 and Th2 lymphocytic infiltrate, with strong exhausted CD8<jats:sup>+<\/jats:sup> signature, and low Th17 and B cell, relative to healthy lymph nodes. Lymphocyte\u2010dominant ALTR\u2010associated synovial fluid contained higher levels of induced protein 10 (IP\u201010), interleukin\u20101 receptor antagonist (IL\u20101RN), IL\u20108, IL\u20106, IL\u201016, macrophage inflammatory protein 1 (MIP\u20101\u03b1), IL\u201018, MCP\u20102, and lower cell\u2010attracting chemokine levels, when compared with prosthetic revisions lacking ALTRs. In addition, the higher levels of IP\u201010, IL\u20108, IL\u20106, MIP\u20101\u03b1, and MCP\u20102 were observed within the synovial fluid of the lymphocyte\u2010dominant ALTRs relative to the macrophage\u2010dominant ALTRs. Not all cytokines\/chemokines were detected in the perivascular aggregate transcripts, suggesting the existence of other sources in the affected synovia. Our results support the hypothesis of common hypersensitivity pathogenesis in lymphocyte\u2010dominant MoM and MoP ALTRs. The exhausted lymphocyte signature indicates chronic processes and an impaired immune response, although the cause of the persistent T\u2010cell activation remains unclear. The cytokine\/chemokine signature of lymphocyte\u2010dominant\u2010associated ATLRs may be of utility for diagnosing this more aggressive pathogenesis.<\/jats:p>","DOI":"10.1002\/jor.24998","type":"journal-article","created":{"date-parts":[[2021,1,28]],"date-time":"2021-01-28T21:57:24Z","timestamp":1611871044000},"page":"2581-2594","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Perivascular lymphocytic aggregates in hip prosthesis\u2010associated adverse local tissue reactions demonstrate Th1 and Th2 activity and exhausted CD8<sup>+<\/sup> cell responses"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7941-561X","authenticated-orcid":false,"given":"Felipe","family":"Eltit","sequence":"first","affiliation":[{"name":"Department of Materials Engineering University of British Columbia  Vancouver British Columbia Canada"},{"name":"School of Biomedical Engineering University of 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