Thymus and activation-regulated chemokine (TARC/CCL17) in mycosis fungoides: serum TARC levels reflect the disease activity of mycosis fungoides.
BACKGROUND
Mycosis fungoides (MF) belongs to cutaneous T-cell lymphoma and is clinically divided into 3 stages: patch, plaque, and tumor stage. Thymus and activation-regulated chemokine (TARC/CCL17) is a member of the CC chemokines and is a chemoattractant for CC chemokine receptor 4 (CCR4)- and CC chemokine receptor 8 (CCR8)-expressing cells.


OBJECTIVE
In this study, we examined the involvement of TARC among patients with each stage of MF.


METHODS
We investigated the expression of TARC, CCR4, and CXC chemokine receptor 3 in patients with each stage of MF by immunohistochemistry. We measured serum TARC levels in 20 patients with MF in varying degrees and compared them with 10 patients with psoriasis vulgaris and 10 healthy controls. In addition, we compared serum TARC levels in patients with MF with other laboratory data.


RESULTS
Immunohistochemical staining revealed that TARC was expressed in the lesional keratinocytes in the patch, plaque, and tumor stages. CCR4 was expressed on the epidermotropic cells in both patch and plaque stages and on the large cell-transformed cells in the tumor stage, whereas CXC chemokine receptor 3 was constantly expressed on the small cells in the lesional dermis. Serum TARC levels in patients with MF were significantly higher than those in patients with psoriasis vulgaris or healthy controls. Moreover, serum TARC levels in patients with the tumor stage of MF (n = 5) were remarkably higher than those with patch stage (n = 8) or plaque stage (n = 7). Serum TARC levels significantly correlated with serum lactate dehydrogenase levels (r = 0.62), serum immunoglobulin E levels (r = 0.60), serum soluble interleukin 2 receptor levels (r = 0.72), and serum macrophage-derived chemokine levels (r = 0.70).


CONCLUSIONS
These data strongly indicate that serum TARC levels are useful for assessing the disease activity of patients with MF and that TARC and CCR4 may be involved in the pathogenesis of MF.
Kakinuma
Takashi
T
Department of Dermatology, University of Tokyo, Japan. KAKINUMAT-DER@h.u-tokyo.ac.jp
Sugaya
Makoto
M
Nakamura
Koichiro
K
Kaneko
Fumio
F
Wakugawa
Motoshi
M
Matsushima
Kouji
K
Tamaki
Kunihiko
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D019742:Chemokines, CC / Q000032:analysis / Q000097:blood* / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007150:Immunohistochemistry; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D008875:Middle Aged; D009182:Mycosis Fungoides / Q000097:blood* / Q000737:chemistry / Q000473:pathology; D011565:Psoriasis / Q000097:blood; D054398:Receptors, CCR4; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000097:blood; D012867:Skin / Q000737:chemistry; D012878:Skin Neoplasms / Q000097:blood* / Q000737:chemistry / Q000473:pathology; D014157:Transcription Factors / Q000032:analysis
C106230:CCL17 protein, human; C515482:CCL22 protein, human; C515354:CCR4 protein, human; C515187:CXCR3 protein, human; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D019742:Chemokines, CC; D054398:Receptors, CCR4; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D015375:Receptors, Interleukin-2; D014157:Transcription Factors; D007073:Immunoglobulin E; D007770:L-Lactate Dehydrogenase