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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  New insight into the role of immune-competent cells in chronic Achilles tendinopathy.
authors: Diagnostic Centre, Silkeborg Regional Hospital, Silkeborg, Denmark maja.kragsnaes@dadlnet.dk.
authors: Maja Skov
authors: MS
authors: Kragsnaes
authors: Diagnostic Centre, Silkeborg Regional Hospital, Silkeborg, Denmark.
authors: Ulrich
authors: U
authors: Fredberg
authors: Institute of Pathology, Aarhus University Hospital, Aarhus, Denmark.
authors: Katrine
authors: K
authors: Stribolt
authors: Diagnostic Centre, Silkeborg Regional Hospital, Silkeborg, Denmark.
authors: Soren Geill
authors: SG
authors: Kjaer
authors: Institute of Pathology, Aarhus University Hospital, Aarhus, Denmark.
authors: Knud
authors: K
authors: Bendix
authors: Diagnostic Centre, Silkeborg Regional Hospital, Silkeborg, Denmark Department of Rheumatology, Odense University Hospital, Odense, Denmark.
authors: Torkell
authors: T
authors: Ellingsen
mesh_terms: D000125:Achilles Tendon / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology*; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001706:Biopsy; D016022:Case-Control Studies; D002908:Chronic Disease; D003430:Cross-Sectional Studies; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006485:Hemosiderin / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007501:Iron / Q000378:metabolism; D007694:Killer Cells, Natural / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D011446:Prospective Studies; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D052256:Tendinopathy / Q000276:immunology / Q000473:pathology*; D014463:Ultrasonography; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; D015214:Antigens, Differentiation, Myelomonocytic; D006485:Hemosiderin; D007501:Iron; C067980:CD68 antigen, human; D000097382:CD68 Molecule
keywords: Achilles tendinopathy; B lymphocytes; NK cells; T lymphocytes; immunohistochemistry; macrophages; mast cells; tendon biopsy