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Hypersensitivity and lymphocyte activation after total hip arthroplasty

Hypersensitivität und lymphozytäre Aktivierung nach Hüftendoprothese

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Abstract

In the last decades total hip arthroplasty (THA) has become a standard procedure with many benefits but also a few still unsolved complications, which can lead to surgical revision in 19–23% of cases. Thus, aseptic loosening and metal hypersensitivity remain challenges. The phenomenon of wear debris causes chronic inflammation, which produces osteolysis and aseptic loosening. Wear debris promotes osteoclast production and inhibits osteoblasts by secretion of pro-inflammatory cytokines. Micro-abrasions can be induced by abrasive, adhesive and fatigue wear and cause a liberation of metal ions, which lead to another immune response elicited mostly by macrophages. Another reaction in the neocapsule can be a type IV hypersensitivity reaction to various alloys, containing metals such as nickel, cobalt and chromium. Patch testing and the lymphocyte transformation test (LTT) are not the best diagnostic possibilities to exclude a postoperative hypersensitivity reaction, because of the different alignment of the epicutaneous cells compared to the periprosthetic deep tissue. This hypersensitivity reaction is mostly induced by cytokines, which are secreted by macrophages rather than lymphocytes. In cell cultures and in animal studies, multipotent mesenchymal stem cells (MSC) have been shown to play a role in improving initial implant integration, to limit periprosthetic osteolysis and also to reconstitute peri-implant bone stock during implant revision. Thus, MSC might be used in the future to prolong the durability of THA. A better understanding of the interactions between primary chronic inflammation, corrosion, osteolysis and hypersensitivity is mandatory to develop new therapeutic strategies, aiming at the reduction of the incidence of implant failures. In this article the underlying immunological mechanisms to aseptic loosening are presented.

Zusammenfassung

In den letzten Jahrzehnten wurde die Implantation einer Hüftendoprothese zu einer der erfolgreichsten Operationen. Eine künstliche Hüfte bringt viele Vorteile, aber auch ungelöste Komplikationen mit sich. Sowohl die aseptische Lockerung des Implantats als auch die Hypersensitivität auf metallische Bestandteile bringen Herausforderungen mit sich, wobei 19–23 % aller Patienten Revisionen benötigen. Aus der Prothese freigesetzte Partikel führen zu einer chronischen Entzündung, die eine Osteolyse und darauffolgende Lockerung der Prothese zur Folge haben kann. Außerdem begünstigen die Abriebbestandteile die Osteoklastenproduktion, während die Osteoblasten, durch Freigabe von entzündungsfördernden Zytokinen, gehemmt werden. Der Mikroabrieb kann durch abrasiven, adhäsiven und Ermüdungsverschleiß entstehen, wobei Metallionen freigesetzt werden, die wiederum eine andere Immunantwort erzwingen, welche vor allem durch Makrophagen ausgelöst wird.

Eine weitere Folge des Verschleißes in der Neokapsel ist die Typ-IV-Hypersensitivitätsreaktion gegenüber verschiedensten Metallen wie Nickel, Cobalt und Chrom. Während der Goldstandard der Diagnostik einer Hypersensitivität der epikutane Patchtest ist, kann auch der LTT („lymphocyte transformation test“) verwendet werden, wobei beide Tests nicht die besten Untersuchungsmöglichkeiten bieten, da die epikutanen Zellen anders aufgebaut sind als das periprothetische Gewebe. Diese typische Hypersensitivitätsreaktion wird fast ausschließlich durch Zytokine ausgelöst, welche wiederum eher durch Makrophagen als durch Lymphozyten freigesetzt werden. In neuesten Zellkulturen und Tierversuchen wurden multipotente mesenchymale Stammzellen (MSCs) untersucht. Diese könnten eine wichtige Rolle in der Implantatfixierung spielen, aber auch dabei helfen, dass die Osteolyse inhibiert wird. Außerdem könnte womöglich auch eine erfolgreiche intraoperative Therapie mit MSC den periimplantären Knochenverlust wiederherstellen. Eine Behandlung mit MSC könnte also letztendlich zu einer Verlängerung der Lebensdauer der Hüftendoprothetik führen. Dafür bedarf es aber eines besseren Verständnisses der primären chronischen Entzündung, Korrosion, Osteolyse und Hypersensitivität. Ohne diese könnten keine neuen therapeutischen Strategien entwickelt werden, damit in Zukunft die Inzidenz des Prothesenversagens vermindert werden kann. Dieser Beitrag widmet sich den immunologischen Mechanismen, die zur aseptischen Prothesenlockerung führen.

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Abbreviations

AP‑1:

Activator protein 1

APC:

Antigen-presenting cells

CPI:

Calpain inhibitor I

GM-CSF:

Granulocyte-macrophage colony stimulating factor

IκB:

Inhibitor of κB

IL:

Interleukin

LTT:

Lymphocyte transformation test

MMP:

Matrix metalloproteinase

MSC:

Mesenchymal stem cells

NF-κB:

Nuclear factor kappa B

OPGL:

Osteoprotegerin ligand

PGE2:

Prostaglandin E2

PMMA:

Poly(methyl methacrylate)

PT:

Patch test

RANKL:

Receptor activator of nuclear factor kappa B ligand

TGF-beta:

Transforming growth factor beta

THA:

Total hip arthroplasty

TJA:

Total joint arthroplasty

TNF:

Tumor necrosis factor

TPCK:

N‑tosyl-L-phenylalanine chloromethyl ketone

UHMWPE:

Ultra-high molecular weight polyethylene

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, Otto-von-Guericke University, Leipziger Str. 44, 39120, Magdeburg, Germany

    Maximilian D. Costa, Jessica Bertrand & Christoph H. Lohmann MD

  2. Centre for Musculoskeletal Surgery, Charité—University Medicine, Berlin, Germany

    Stefanie Donner

  3. Department of Morphological Sciences, Faculty of Medicine and Pharmacy, University of Oradea, Oradea, Romania

    Maximilian D. Costa & Ovidiu-Laurean Pop

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  1. Maximilian D. Costa
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Correspondence to Christoph H. Lohmann MD.

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M.D. Costa, S. Donner, J. Bertrand, O.-L. Pop and C.H. Lohmann declare that they have no competing interests.

For this article no studies with human participants or animals were performed by any of the authors. All studies mentioned were in accordance with the ethical standards indicated in each case.

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Costa, M.D., Donner, S., Bertrand, J. et al. Hypersensitivity and lymphocyte activation after total hip arthroplasty. Orthopädie 52, 214–221 (2023). https://doi.org/10.1007/s00132-023-04349-7

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