Perivascular lymphocytic aggregates in hip prosthesis‐associated adverse local tissue reactions demonstrate Th1 and Th2 activity and exhausted CD8<sup>+</sup> cell responses
Bibliographic record
Abstract
Abstract Hip implants are a successful solution for osteoarthritis; however, some individuals with metal‐on‐metal (MoM) and metal‐on‐polyethylene (MoP) prosthetics develop adverse local tissue reactions (ALTRs). While MoM and MoP ALTRs are presumed to be delayed hypersensitivity reactions to corrosion products, MoM‐ and MoP‐associated ALTRs present with different histological characteristics. We compared MoM‐ and MoP‐associated 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‐dominant, mixed, and lymphocyte‐dominant. Immune‐related transcript profiles from lymphocyte‐dominant MoM‐ and MoP‐associated ALTR patients with perivascular lymphocytic aggregates were similar. Cell signatures indicated predominantly macrophage, Th1 and Th2 lymphocytic infiltrate, with strong exhausted CD8+ signature, and low Th17 and B cell, relative to healthy lymph nodes. Lymphocyte‐dominant ALTR‐associated synovial fluid contained higher levels of induced protein 10 (IP‐10), interleukin‐1 receptor antagonist (IL‐1RN), IL‐8, IL‐6, IL‐16, macrophage inflammatory protein 1 (MIP‐1α), IL‐18, MCP‐2, and lower cell‐attracting chemokine levels, when compared with prosthetic revisions lacking ALTRs. In addition, the higher levels of IP‐10, IL‐8, IL‐6, MIP‐1α, and MCP‐2 were observed within the synovial fluid of the lymphocyte‐dominant ALTRs relative to the macrophage‐dominant 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‐dominant MoM and MoP ALTRs. The exhausted lymphocyte signature indicates chronic processes and an impaired immune response, although the cause of the persistent T‐cell activation remains unclear. The cytokine/chemokine signature of lymphocyte‐dominant‐associated ATLRs may be of utility for diagnosing this more aggressive pathogenesis.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".