Stereological quantification of immune-competent cells in baseline biopsy specimens from achilles tendons: results from patients with chronic tendinopathy followed for more than 4 years

Maja Skov Kragsnaes, Ulrich Fredberg, Katrine Stribolt, Soren Geill Kjaer, Knud Bendix, Torkell Ellingsen

Research output: Contribution to journalJournal articleResearchpeer-review

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.

Original languageEnglish
JournalAmerican Journal of Sports Medicine
Volume42
Issue number10
Pages (from-to)2435-45
ISSN0363-5465
DOIs
Publication statusPublished - 2014

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Achilles Tendon
Macrophages
Mast Cells
Iron
Schwann Cells
Case-Control Studies

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@article{6629ff04be164e4597ff09abfe4a0ac5,
title = "Stereological quantification of immune-competent cells in baseline biopsy specimens from achilles tendons: results from patients with chronic tendinopathy followed for more than 4 years",
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.",
author = "Kragsnaes, {Maja Skov} and Ulrich Fredberg and Katrine Stribolt and Kjaer, {Soren Geill} and Knud Bendix and Torkell Ellingsen",
note = "{\circledC} 2014 The Author(s).",
year = "2014",
doi = "10.1177/0363546514542329",
language = "English",
volume = "42",
pages = "2435--45",
journal = "American Journal of Sports Medicine",
issn = "0363-5465",
publisher = "SAGE Publications",
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}

Stereological quantification of immune-competent cells in baseline biopsy specimens from achilles tendons : results from patients with chronic tendinopathy followed for more than 4 years. / Kragsnaes, Maja Skov; Fredberg, Ulrich; Stribolt, Katrine; Kjaer, Soren Geill; Bendix, Knud; Ellingsen, Torkell.

In: American Journal of Sports Medicine, Vol. 42, No. 10, 2014, p. 2435-45.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Stereological quantification of immune-competent cells in baseline biopsy specimens from achilles tendons

T2 - results from patients with chronic tendinopathy followed for more than 4 years

AU - Kragsnaes, Maja Skov

AU - Fredberg, Ulrich

AU - Stribolt, Katrine

AU - Kjaer, Soren Geill

AU - Bendix, Knud

AU - Ellingsen, Torkell

N1 - © 2014 The Author(s).

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

U2 - 10.1177/0363546514542329

DO - 10.1177/0363546514542329

M3 - Journal article

C2 - 25081311

VL - 42

SP - 2435

EP - 2445

JO - American Journal of Sports Medicine

JF - American Journal of Sports Medicine

SN - 0363-5465

IS - 10

ER -