Stereological Quantification of Immune-Competent Cells in Baseline Biopsy Specimens From Achilles Tendons

Abstract

Background: Limited data exist on the presence and function of immune-competent cells in chronic tendinopathic tendons and their potential role in inflammation and tissue healing as well as in predicting long-term outcome. Purpose: To quantify subtypes of immune-competent cells in biopsy specimens from nonruptured chronic tendinopathic Achilles tendons and healthy control tendons. In addition, to examine whether findings in baseline cell biopsy specimens can predict the long-term presence of Achilles tendon symptoms. Study Design: Cross-sectional and case-control study; Level of evidence, 3. Methods: Fifty patients with nonruptured chronic Achilles tendinopathy and 15 healthy participants were included. At time of inclusion, an ultrasound examination was performed immediately before an ultrasound-guided Achilles tendon biopsy specimen was obtained. Tissue samples were evaluated immunohistochemically by quantifying the presence of macrophages (CD68-PGM1+, CD68-KP1+), hemosiderophages (Perls blue), T lymphocytes (CD2+, CD3+, CD4+, CD7+, CD8+), B lymphocytes (CD20+), natural killer cells (CD56+), mast cells (NaSDCl+), Schwann cells (S100+), and endothelial cells (CD34+) using a stereological technique. A follow-up examination was conducted more than 4 years (range, 4-9 years) after the biopsy procedure to evaluate the long-term presence of Achilles tendon symptoms. Results: Macrophages, T lymphocytes, mast cells, and natural killer cells were observed in the majority (range, 52%-96%) of biopsy specimens from nonruptured chronic tendinopathic Achilles tendons. CD68-KP1+ macrophages (0.29% vs 0; P = .005) and CD34+ endothelial cells (3% vs 0.97%; P = .04) were significantly more numerous in tendinopathic tendons compared with healthy tendons. The presence of iron+ hemosiderophages was more frequently observed in biopsy specimens obtained from the group who was asymptomatic at follow-up compared with the symptomatic group (42% vs 5%; P = .02). Conclusion: This study provides evidence for the presence of immune-competent cells in the majority of biopsy specimens from nonruptured chronic tendinopathic Achilles tendons. Macrophages and endothelial cells were significantly more numerous in tendinopathic tendons than in healthy tendons. The presence of iron+ hemosiderophages in baseline biopsy specimens was associated with a good prognosis. Clinical Relevance: New insight into the role of immune-competent cells in chronic Achilles tendinopathy.