Higher densities of T-lymphocytes in the subsynovial connective tissue of people with carpal tunnel syndrome

PLoS One. 2024 Mar 7;19(3):e0300046. doi: 10.1371/journal.pone.0300046. eCollection 2024.

Abstract

Symptoms in people with carpal tunnel syndrome (CTS) are traditionally attributed to neural tissue, but recent studies suggest that the subsynovial connective tissue (SSCT) may also play a role in CTS. The SSCT undergoes fibrotic thickening which is generally described as "non-inflammatory" based on basic histology. This study uses immunohistochemistry to determine the presence of macrophages and T-cells within SSCT and their relationship with symptoms in people with CTS. SSCT was collected from twenty people with CTS and eight controls undergoing wrist fracture surgery. Immunohistochemical quantification of CD3+ T-cells and CD68+ macrophage densities as well as CD4+/CD8+ T-cell subpopulations were compared between groups using independent t-tests. Spearman correlations were used to identify associations between immune cell densities and CTS symptom scores. The density of CD3+ T-cells was significantly higher in SSCT of people with CTS compared to controls (CTS mean 26.7 (SD 13.7); controls 6.78 (6.3), p = 0.0005) while the density of CD68+ macrophages was lower (CTS mean 9.5 (SD 6.0); controls 17.7 (8.2), p = 0.0058). Neither CD68+ nor CD3+ cell densities correlated with symptom scores. In contrast to previous assumptions, our data show that the SSCT in the carpal tunnel in both people with CTS and controls is not devoid of immune cells. Whereas the higher density of CD68+ macrophages in control participants may be associated with their early recruitment after acute fracture, CD3+ cells within the SSCT may play a role in chronic CTS.

MeSH terms

  • Carpal Tunnel Syndrome* / surgery
  • Connective Tissue
  • Humans
  • Synovial Membrane
  • Wrist
  • Wrist Injuries*

Grants and funding

ABS is supported by a Wellcome Trust Clinical Career Development Fellowship (222101/Z/20/Z) and the Medical Research Foundation (MRF-160-0013-ELP-SCHM-C0842; Emerging Leaders Prize in Pain Research). AW is supported by a National Institute for Health Research (NIHR) Clinical Lectureship. MMA is supported by URJC Predoctoral Grant and by the co-financed Grant by Banco Santander and the URJC's Escuela Internacional de Doctorado to obtain the title of International Doctor. None of the funders had any involvement in the study design, data collection, analysis, interpretation, writing of the manuscript and the decision to submit for publication. Statement: This research was funded in whole, or in part, by the Wellcome Trust [222101/Z/20/Z]. For the purpose of Open Access, the author has applied a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission.