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In vitro reactivity to implant metals demonstrates a person‐dependent association with both T‐cell and B‐cell activation
Author(s) -
Hallab Nadim James,
Caicedo Marco,
Epstein Rachel,
McAllister Kyron,
Jacobs Joshua J.
Publication year - 2010
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.32368
Subject(s) - t cell , cell growth , metal , cd69 , cell , materials science , stimulation , immunology , il 2 receptor , medicine , chemistry , immune system , biochemistry , metallurgy
Abstract Hypersensitivity to metallic implants remains relatively unpredictable and poorly understood. We initially hypothesized that metal‐induced lymphocyte proliferation responses to soluble metal challenge (ions) are mediated exclusively by early T‐cell activation (not B‐cells), typical of a delayed‐type‐hypersensitivity response. We tested this by comparing proliferation (6 days) of primary lymphocytes with early T‐cell and B‐cell activation (48 h) in three groups of subjects likely to demonstrate elevated metal reactivity: group 1 ( n = 12) history of metal sensitivity with no implant; group 2a ( n = 6) well performing metal‐on‐metal THRs, and group 2b ( n = 20) subjects with poorly performing metal‐on‐polymer total joint arthroplasties (TJA). Group 1 showed 100% (12/12) metal reactivity (stimulation index > 2) to Ni. Groups 2a and 2b were 83% (5/6) and 75% (15/22) metal reactive (to Co, Cr, or Ni), respectively. Of the n = 32 metal‐reactive subjects to Co, Cr, or Ni (SI > 2), n = 22/32 demonstrated >2‐fold elevations in % of T‐cell or B‐cell activation (CD25+, CD69+) to metal challenge when compared with untreated control. 18/22 metal‐activated subjects demonstrated an exclusively T‐cell or B‐cell activation response to metal challenge, where 6/18 demonstrated exclusively B‐cell activation and 12/18 demonstrated a T‐cell only response, as measured by surface activation markers CD25+ and CD69+. However, there was no direct correlation ( R 2 < 0.1) between lymphocyte proliferation and % T‐cell or B‐cell activation (CD25+:CD69+). Proliferation assays (LTT) showed greater ability to detect metal reactivity than did subject‐dependent results of flow‐cytometry analysis of T‐cell or B‐cell activation. The high incidence of lymphocyte reactivity and activation indicate that more complex than initially hypothesized immune responses may contribute to the etiology of debris‐induced osteolysis in metal‐sensitive individuals. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010