Relationships among plasma granzyme B level, pruritus and dermatitis in patients with atopic dermatitis.
BACKGROUND
Atopic dermatitis (AD) is a multifactorial inflammatory skin disease characterized by skin barrier dysfunction, allergic inflammation and intractable pruritus resistant to conventional antipruritic treatments, including H1-antihistamines. Granzymes (Gzms) are a family of serine proteases expressed by cytotoxic T lymphocytes and natural killer cells that have been shown to modulate inflammation. However, the relationship between Gzms and pathology in AD remains unclear.


OBJECTIVE
This study assessed the correlation between plasma GzmB levels and severity of pruritus and dermatitis, in AD patients.


METHODS
Plasma was collected from 46 patients with AD, 24 patients with psoriasis, and 30 healthy controls. AD severity was assessed with the scoring atopic dermatitis (SCORAD) index, psoriasis severity with the psoriasis area and severity index (PASI), and degree of pruritus by visual analogue scale (VAS) score. GzmA, GzmB and gastrin releasing peptide (GRP) levels were measured by enzyme-linked immunosorbent assays.


RESULTS
Plasma GzmB concentrations were significantly higher in patients with AD and psoriasis than in healthy controls. Correlation analyses showed that plasma GzmB concentrations positively correlated with SCORAD and serum levels of severity markers such as thymus and activation-regulated chemokine, and lactate dehydrogenase in AD patients. Moreover, plasma levels of GRP, an itch-related peptide, were higher in patients with AD, positively correlating with VAS score and plasma GzmB level. In addition, plasma GzmB concentration was significantly lower in the treatment group than the untreated group with AD. Meanwhile, there were no correlations among GzmB levels, VAS score and PASI score in patients with psoriasis. In contrast to the results of plasma GzmB, plasma GzmA levels were unchanged among AD, psoriasis and healthy groups, and showed no correlations with VAS score and SCORAD index in patients with AD.


CONCLUSIONS
Plasma GzmB levels may reflect the degree of pruritus and dermatitis in patients with AD.
Institute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan.
Yayoi
Y
Kamata
Department of Dermatology, Juntendo University Urayasu Hospital, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan.
Utako
U
Kimura
Institute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan.
Hironori
H
Matsuda
Institute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan.
Suhandy
S
Tengara
Institute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan.
Atsuko
A
Kamo
Institute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan.
Yoshie
Y
Umehara
Institute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan.
Kyoichi
K
Iizumi
Institute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan.
Hiroaki
H
Kawasaki
Department of Dermatology, Juntendo University Urayasu Hospital, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan.
Yasushi
Y
Suga
Institute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan.
Hideoki
H
Ogawa
Institute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan. Electronic address: tominaga@juntendo.ac.jp.
Mitsutoshi
M
Tominaga
Institute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan; Department of Dermatology, Juntendo University Urayasu Hospital, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan. Electronic address: ktakamor@juntendo.ac.jp.
Kenji
K
Takamori
D000328:Adult; D016022:Case-Control Studies; D003872:Dermatitis / Q000097:blood* / Q000276:immunology; D003876:Dermatitis, Atopic / Q000097:blood* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019886:Gastrin-Releasing Peptide / Q000097:blood; D005786:Gene Expression Regulation; D053804:Granzymes / Q000097:blood*; D006801:Humans; D007249:Inflammation; D007694:Killer Cells, Natural / Q000166:cytology; D008297:Male; D008875:Middle Aged; D011537:Pruritus / Q000097:blood* / Q000276:immunology; D011565:Psoriasis / Q000097:blood* / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology
D019886:Gastrin-Releasing Peptide; C509213:GZMB protein, human; D053804:Granzymes
Atopic dermatitis; Granzyme B; Itch; Plasma; VAS score