Increased CCL18 expression in patients with cutaneous T-cell lymphoma: association with disease severity and prognosis

J Eur Acad Dermatol Venereol. 2013 Jan;27(1):e60-7. doi: 10.1111/j.1468-3083.2012.04495.x. Epub 2012 Mar 9.

Abstract

Background: CC chemokine ligand (CCL) 18 is expressed by monocytes and dendritic cells (DCs), and has potent chemotactic activity for T cells, B cells and DCs. CCL18 expression is up-regulated in lesional skin of atopic dermatitis and bullous pemphigoid, suggesting its important roles in the development of these skin diseases.

Objective: To investigate roles of CCL18 in cutaneous T-cell lymphoma (CTCL).

Methods: The CCL18 messenger RNA (mRNA) expression in CTCL skin (n = 21) and in normal skin (n = 7) was examined by quantitative RT-PCR. CCL18 expression was also examined by immunohistochemistry. Serum CCL18 levels were measured in 38 patients with CTCL and 20 healthy controls by enzyme-linked immunosorbent assay. We also analysed correlation between serum CCL18 levels and other clinical and laboratory data.

Results: The CTCL lesional skin contained higher levels of CCL18 mRNA than normal skin. CCL18 was expressed by dermal macrophages and DCs in CTCL skin. Serum CCL18 levels in patients with CTCL were significantly higher than those of healthy controls and correlated with types of skin lesions. They also significantly correlated with modified severity-weighted assessment scores, serum sIL-2R, LDH, IL-4, IL-10, IL-31, CCL17 and CCL26 levels. Patients with high serum levels of CCL18 showed significantly poor prognosis compared with those with low CCL18 levels.

Conclusion: CCL18 mRNA is up-regulated in CTCL lesional skin, and serum CCL18 levels are significantly increased and correlated with the severity of CTCL. These results suggest that CCL18 may be associated with the development of CTCL.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biopsy, Needle
  • Case-Control Studies
  • Chemokines, CC / genetics*
  • Chemokines, CC / metabolism
  • Disease Progression
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry
  • Lymphoma, T-Cell, Cutaneous / genetics*
  • Lymphoma, T-Cell, Cutaneous / pathology
  • Lymphoma, T-Cell, Cutaneous / physiopathology
  • Male
  • Middle Aged
  • Neoplasm Invasiveness / pathology
  • Prognosis
  • RNA, Messenger / metabolism
  • Real-Time Polymerase Chain Reaction / methods
  • Reference Values
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / pathology
  • Skin Neoplasms / physiopathology
  • Statistics, Nonparametric
  • Up-Regulation

Substances

  • CCL18 protein, human
  • Chemokines, CC
  • RNA, Messenger