So, “hip implant rejection” usually refers to loosening, inflammatory reaction to debris/ions, hypersensitivity, or infection, rather than classic transplant rejection.
Adaptive immunity can contribute (especially in metal hypersensitivity), but most implant failure is not antigen-specific “allorecognition”.
1) T-cell–mediated rejection (cell-mediated) - CD8+ T cells can directly kill graft cells. - CD4+ T helper cells amplify inflammation via cytokines (e.g., IFN-γ, TNF) and recruit macrophages. - Results: parenchymal injury, interstitial inflammation, endothelial activation.
2) Antibody-mediated rejection (humoral) - Recipient B cells produce donor-specific antibodies (DSA), often targeting HLA. - Antibodies bind graft endothelium → complement activation (classically C4d deposition is a histological clue in some organs) and microvascular injury. - Leads to thrombosis, capillary leak, and progressive scarring.
Sequence 1. Protein adsorption: within seconds, host proteins coat the implant surface. 2. Acute inflammation (hours–days): neutrophils may appear initially (especially if surgical trauma). 3. Chronic inflammation (days–weeks): macrophages dominate. 4. Foreign-body giant cells: macrophages fuse when they cannot phagocytose large surfaces/particles. 5. Fibrous encapsulation: fibroblasts lay down collagen around the implant (a “capsule”); this can be stable or problematic depending on location.
This response is largely innate and non-antigen-specific.
Hip prostheses generate microscopic debris over time: - Polyethylene particles (common in conventional bearings) - Metal particles/ions (from wear or corrosion at modular junctions) - Ceramic particles (less common; usually low volume)
Mechanism - Macrophages ingest particles → activation of inflammatory pathways (including inflammasome signalling in some contexts) → cytokine release. - Key mediators include TNF-α, IL‑1β, IL‑6 and chemokines that recruit more macrophages. - Critically, inflammation promotes osteoclast formation via the RANK/RANKL/OPG axis: - Increased RANKL (from stromal cells/osteoblast lineage cells and activated immune cells) stimulates osteoclast differentiation. - Osteoclasts resorb periprosthetic bone → periprosthetic osteolysis. - Bone loss reduces fixation → micromotion → more wear and further inflammation (a vicious cycle).
This is called aseptic loosening when infection is not the cause.
Key cell types - Macrophages, foreign-body giant cells - Fibroblasts (fibrous membrane formation) - Osteoclasts (bone resorption) - Variable lymphocytes (usually fewer than in classic transplant rejection, except in hypersensitivity patterns)
Particularly discussed with certain metal-on-metal bearings or modular junction corrosion: - Metal ions (e.g., cobalt/chromium) can be cytotoxic and pro-inflammatory. - Can trigger ALTR/ARMD (adverse reaction to metal debris): soft-tissue inflammation, necrosis, pseudotumour-like masses in some cases. - Histology may show macrophage infiltrates; sometimes a lymphocyte-rich pattern (see below).
A minority of patients develop an immune pattern closer to adaptive immunity: - Typically Type IV (delayed-type) hypersensitivity (T-cell mediated) to metal-protein complexes (haptenisation). - Histology in some cases shows lymphocyte-predominant inflammation (often described as ALVAL in certain contexts: aseptic lymphocyte-dominated vasculitis-associated lesion). - This is still not “rejection” of living tissue, but rather an immune response to metal-associated antigens. - Clinical relevance is debated: positive skin patch tests do not always correlate with implant failure, and symptoms overlap with other causes.
Prosthetic joint infection (PJI) may be acute or indolent: - Bacteria can form biofilms on implant surfaces, making them harder to culture and more resistant to antibiotics. - Infection drives persistent inflammation, pain, loosening and sometimes systemic features. - This is not immune rejection; it is host response to microbes plus bacterial persistence.