Immune cell populations differ in patients undergoing revision total knee arthroplasty for arthrofibrosis

Abstract

Arthrofibrosis following total knee arthroplasty (TKA) is a debilitating condition typically diagnosed based on clinical findings. To gain insight into the histopathologic immune cell microenvironment of arthrofibrosis, we assessed the extent of tissue fibrosis and quantified immune cell populations in specific tissue regions of the posterior capsule. We investigated specimens from three prospectively-collected, matched cohorts, grouped as patients receiving a primary TKA for osteoarthritis, revision TKA for arthrofibrosis, and revision TKA for non-arthrofibrotic, non-infectious reasons. Specimens were evaluated using hematoxylin and eosin staining, picrosirius red staining, immunofluorescence, and immunohistochemistry with Aperio®-based digital image analysis. Increased collagen deposition and increased number of α-SMA/ACTA2 expressing myofibroblasts were present in the arthrofibrosis group compared to the two non-arthrofibrotic groups. CD163 + macrophages were the most abundant immune cell type in any capsular sample with specific enrichment in the synovial tissue. CD163 + macrophages were significantly decreased in the fibrotic tissue region of arthrofibrosis patients compared to the patients with primary TKA, and significantly increased in adipose tissue region of arthrofibrotic specimens compared to non-arthrofibrotic specimens. Synovial CD117 + mast cells were significantly decreased in arthrofibrotic adipose tissue. Together, these findings inform diagnostic and targeted therapeutic strategies by providing insight into the underlying pathogenetic mechanisms of arthrofibrosis.

Single-cell and bulk tissue sequencing unravels the heterogeneity of synovial microenvironment in arthrofibrosis

“…Recent researchers have illustrated that mononuclear phagocytes, especially activated M1 macrophages, are important in AF initiation and maintenance. 43 , 44 Clinical studies have demonstrated a positive correlation between M1 macrophage tissue density and preoperative patient-reported KSS outcomes. 44 In this study, we identified the M1-like F-Mφ subcluster as the key driver cell type of AF pathogenesis.…”

“… 43 , 44 Clinical studies have demonstrated a positive correlation between M1 macrophage tissue density and preoperative patient-reported KSS outcomes. 44 In this study, we identified the M1-like F-Mφ subcluster as the key driver cell type of AF pathogenesis. It is widely accepted that macrophages are not only permanent cells, that can transfer from M0 to M1/M2.…”

“…Samples were fixed by immersion in neutral-buffered 10% formalin for 48 h at room temperature, and processed into paraffin per standard histology protocols. 44 The workflow of this study is shown in Figure S1 . This work was approved by the Ethics Committee of Jishuitan Hospital (No.201811-09) with registration.…”

Arthrofibrosis After Total Knee Arthroplasty

“…Immune system–related biomarkers, including cytokines and immune cell populations, have also been investigated 92,98 . The innate 99 and adaptive 91,100 immune systems have been implicated in developing arthrofibrosis. In preliminary studies of arthrofibrosis biomarkers, patient cohorts have included those undergoing rTKA for arthrofibrosis compared with primary TKA patients with osteoarthritis and rTKA patients with nonfibrotic etiologies 48 .…”

“…Salib et al found similar inflammatory marker profiles in the synovial fluid and serum of patients with and without arthrofibrosis 98 . Limberg et al showed that the fibrotic tissue and synovial fluid of patients with arthrofibrosis had decreased CD163+ macrophages and CD177+ mast cells, suggesting differential immune cell populations 99 . Seeking to characterize the adaptive immune response, Jenkins et al found increased levels of immunoglobulin (Ig) G1, IgG3, and anti-phosphatidyl serine IgG in the synovial fluid of patients with arthrofibrosis, from which they concluded that intra-articular interactions of T and B cells could be a source of immune complexes affecting scarring after TKA 100 .…”