Expression of ICAM-3/CD50 in normal and diseased skin

ICAM-3 is a newly recognized adhesion molecule, which is a member of the immunoglobulin supergene family of ICAMs. and has been shown to be identical with the CD50 antigen. Recent functional studies have shown that ICAM-3 is a ligand for LFA-1, and plays an important part in immune reactions. To date, very few data exist in the literature concerning its expression in the skin. In the present study, we investigated the expression of ICAM-3 in normal skin and in 98 biopsy specimens of various inflammatory and neoplastic dermatoses. ICAM-3 was found to be expressed by epidermal CD la⁺ Langerhans cells, by cells of Langerhans cell hisliocytosis, by T and B lymphocytes infiltrating the dermis in cutaneous lymphomas and in a wide spectrum of inflammatory dermaloses. Epidermal keralinocytes were consistently negative: endothelial expression of ICAM-3 was observed in six of the 48 cases. These results show that ICAM-3 is constitutively and widely expressed by cells participating in inflammatory dermaloses (including Langerhans cells and T and B lymphocytes), and that it can be albeit rarely, induced on endothelial cells and dermal dendrocytes. These results highlight the important part that ICAM-3 may play in cutaneous inflammatory and immune reactions.     

Dermal infiltrates of cutaneous T‐cell lymphomas with epidermotropism but not other cutaneous lymphomas are abundant with langerin+ dendritic cells

Background The Langerhans cell (LC) hypothesis suggests that cutaneous T‐cell lymphomas (CTCL) are diseases of chronic T‐cell stimulation by LC‐mediated antigen presentation. Objective To investigate a broad panel of CTCL and cutaneous B‐cell lymphomas (CBCL) for the spatial association of langerin⁺ dendritic cells (DC) with T and B cells in the skin, respectively. Methods Fifty‐five specimens of CTCL and 10 of CBCL were double‐stained with monoclonal antibodies against langerin and CD3 or CD20, respectively, and evaluated by confocal laser scan microscopy. Results Dermal infiltrates in mycosis fungoides (n = 38), primary cutaneous CD4+ small/medium‐sized pleomorphic T‐cell lymphoma (n = 3) and primary cutaneous peripheral T‐cell lymphoma, unspecified (n = 3) were characterized by a high frequency of dermal langerin⁺ DCs. These cells were exclusively present in the malignant infiltrates. No direct co‐localization of CD3 and langerin could be resolved. Dermal langerin⁺ cells were detected only in one of six primary cutaneous anaplastic large cell lymphomas (C‐ALCL), characterized by epidermotropism. In other C‐ALCL cases (five of six), in lymphomatoid papulosis (n = 3), subcutaneous panniculitis‐like T‐cell lymphoma (n = 2), and all variants of CBCL no dermal langerin⁺ DCs could be found. Conclusions Langerin⁺ DCs are abundant in the dermal infiltrates of T‐cell lymphomas with specific involvement of the epidermis. This might indicate that immature LC and neoplastic T cells interact and gives rise to further studies to characterize the phenotype of the langerin⁺ cell population described here and its role in the pathology of CTCL.     

In situ depletion of CD4<Superscript>+</Superscript> T cells in human skin by Zanolimumab

CD4⁺ T cells, in activated or malignant form, are involved in a number of diseases including inflammatory skin diseases such as psoriasis, and T cell lymphomas such as the majority of cutaneous T cell lymphomas (CTCL). Targeting CD4 with an antibody that inhibits and/or eliminates disease-driving T cells in situ may therefore be a useful approach in the treatment of inflammatory and malignant skin diseases. Depletion of CD4⁺ T cells in intact inflamed human skin tissue by Zanolimumab, a fully human therapeutic monoclonal antibody (IgG1, κ) against CD4, was studied in a human psoriasis xenograft mouse model. Zanolimumab treatment was shown to induce a significant reduction in the numbers of inflammatory mononuclear cells in upper dermis. This reduction in inflammatory mononuclear cells in situ was primarily due to a significant reduction in the numbers of skin-infiltrating CD4⁺, but not CD8⁺ CD3⁺ T cells. The capacity of Zanolimumab to deplete the CD4⁺ T cells in the skin may be of importance in diseases where CD4⁺ T cells play a central role. Indeed, in a phase II clinical trial Zanolimumab has shown a dose-dependent clinical response in patients with CTCL and the antibody is currently in a phase III clinical trial for CTCL, a disease for which there is no safe and effective treatment available today.     

Lymphocytes and macrophages of the epidermis and dermis in lesional psoriatic skin,but not epidermal Langerhans cells,are depleted by treatment with cyclosporin A

Summary Since cyclosporin A (CsA) is an immuno-suppressive agent, its beneficial effect in psoriasis suggests that immune cells may play a role in the pathogenesis and resolution of psoriasis. To determine early effects of CsA in psoriasis, we quantitated immune cells using double immunofluorescence microscopy on biopsy specimens obtained prior to therapy and after 3,7, and 14 days of CsA therapy. CsA therapy resulted in significant reductions in the absolute number of immune cells (including T cells, monocytes/macrophages, and antigen presenting cells) contained within psoriatic skin. The effect was rapid, with over one-half of the reduction in the density of HLe1⁺ (human leukocyte antigen-1 positive or bone marrow derived) cells, including T cells, activated T cells, monocytes, and Langerhans cells (LCs), occurring within 3 days. Despite the overall reduction in the numbers of immunocytes in the skin, the proportion of T cells, Langerhans cells, and monocytes in relation to the total number of immune cells was unchanged with therapy, reflecting equally proportional losses of each subtype. Dermal CD1⁺DR⁺ cells (putative Langerhans cells), which are not found in normal skin but are present in lesional psoriasis skin, were virtually cleared from the papillary dermis after CsA therapy. Although absolute numbers of epidermal Langerhans cells, defined as cells expressing both CD1 (T6) and DR molecules (CD1⁺DR⁺), were also reduced after CsA, epidermal non-Langerhans CD1^-DR⁺ cells (macrophages, activated T cells, DR^- keratinocytes) demonstrated a proportionally greater decrease, with the ratio of CD1⁺DR⁺ Langerhans cells/non-Langerhans CD1^-DR⁺ epidermal cells changing from a mean of 0.82 at baseline to 1.92 at day 14. Thus, early in the course of therapy, CsA appears to be effective at clearing CD1^-DR⁺ cells while leaving LC relatively intact in the epidermis.This work was supported in part by the Babcock Foundation     

Immunohistochemical characterization of non‐epithelial cells in spiradenoma

Spiradenoma is unique with respect to the presence of a large number of non‐epithelial cells, including S100 protein⁺ cells, most of which are presumably Langerhans cells, in the parenchyma as shown in the published work. However, the characterization of these non‐epithelial cells to date is insufficient. Immunohistochemistry of CD1a, CD3, CD4, CD8, CD56, CD68, intercellular adhesion molecule‐1 (ICAM‐1), and HLA‐DR, as well as double‐immunofluorescence labeling of S100 protein/CD1a and CD1a/CD3, was performed using paraffin‐embedded specimens from five cases of spiradenoma retrospectively. Non‐epithelial cells evenly distributed throughout the parenchyma of spiradenoma primarily consisted of CD1a⁺ Langerhans cells and CD3⁺ T cells. ICAM‐1 was expressed by epithelial cells and non‐epithelial cells in the parenchyma. HLA‐DR on the epithelial cells was limited to the focal area. In double‐immunofluorescence labeling, approximately one‐half of Langerhans cells were spatially related to T cells in the parenchyma, suggesting their functional interaction.     

About the cutaneous targets of bexarotene in CTCL patients

Please cite this paper as: About the cutaneous targets of bexarotene in CTCL patients. Experimental Dermatology 2010; 19 : e299–e301. Abstract: There are several approved therapies for cutaneous T‐cell lymphoma (CTCL). The retinoids are one of the major biologic response modifiers used in CTCL, producing good response rates but few complete responses. Bexarotene has been demonstrated to act on malignant T‐cells by inducing their apoptosis, but nothing is known about its role on keratinocytes and Langerhans cells. Immunohistochemical analysis using CD1a, HLA‐DR, ICAM‐1 (activation markers), CD95 and CD40 (apoptosis markers) was conducted on frozen sections of bexarotene‐exposed cutaneous explants and skin biopsy specimens from patients treated with bexarotene. None of the studied markers was significantly modulated both on cutaneous explants and on skin biopsy specimens after treatment with bexarotene, compared to controls. Langerhans cells and keratinocytes do not appear to play a central role in the therapeutic control of CTCL by bexarotene therapy. The main bexarotene’s target thus remains T‐cells by inducing their apoptosis, a mechanism that is different from the other retinoids used in CTCL.     

Tumour necrosis factor alpha is pro-inflammatory in normal human skin and modulates cutaneous adhesion molecule expression

Tumour necrosis factor a (TNF-α) is a potent immunoregulatory cytokine produced by many cutaneous cells, including kcratinocytes, mast cells and Langerhans cells. To explore its potential role in inflammatory skin disease, we have studied immunohistochemically the effects of intradermal recombinant human TNF-α (rHuTNF-α) on cutaneous inflammatory cells, adhesion molecules and Langerhans cells in normal human skin. Volunteers received rHuTNF-α 100U (group A), 5000 U (group B), or 100 U daily for 5 days (group C), and biopsies were taken at 6 h (groups A and B), or 6 h after the final injection (group C). An inflammatory cell infiltrate developed in all cases: following single injections of either 100 or 5000 U rHuTNF-α this was predominantly neutrophilic, whereas following multiple injections of 100 U few neutrophils were seen, although many lymphocytes (CD3⁺, CD4⁴) were present. In all groups there was an increase in cells of monocyte/macrophage lineage (CD36⁾⁺. TNF-α induced a dose- and time-dependent decrease in CDla⁺ epidermal Langerhans cell numbers and an increase in dermal CDla⁴ cells, suggesting migration of Langerhans cells away from the epidermis. TNF-α induced endothelial E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in all groups, and adhesion molecule expression by interstitial dermal dendritic cells (ICAM-1 and VCAM-1) and keratinocytes (ICAM-1) was observed. These findings indicate that TNF-α is a potent modulator of cutaneous immune function in vivo, and this central role in the cutaneous immune response suggests that TNF-α may be an attractive target for therapeutic inhibition.     

Epidermal dendritic cells in psoriasis possess a phenotype associated with antigen presentation: in situ expression of beta 2-integrins.

BACKGROUND: Epidermal dendritic cells (DCs) isolated from psoriasis possess greatly enhanced T lymphocyte-activating properties compared with DCs from normal skin, suggesting that DCs in psoriasis express surface antigens crucial for antigen presentation. These include beta 2-integrins and intercellular adhesion molecule (ICAM)-1. OBJECTIVE: Our purpose was to determine DC phenotype in psoriatic compared with normal epidermis with respect to these molecules. METHODS: Tissue sections were single labeled with a peroxidase antiperoxidase (PAP) immunohistochemical technique and double labeled where necessary with a combination of a PAP and an alkaline phosphatase-anti-alkaline phosphatase technique. RESULTS: In psoriatic compared with normal skin, decreased numbers of DCs expressed CD1a (p less than 0.05), whereas increased numbers of DCs expressed class II major histocompatibility antigens (p less than 0.05). In normal skin positive staining for CD18 was not observed, whereas in psoriasis both CD1a+ and CD1a- DCs expressed beta 2-integrins, LFA-1 (CD11a/CD18), and gp 150/95 (CD11c/CD18). DCs in atopic dermatitis and lichen planus were also found to express beta 2-integrins. Neither MAC 1 (CD11b/CD18) nor ICAM-1 was observed on DCs. CONCLUSION: These data are consistent with either migration of dendritic antigen-presenting cells into the epidermis or in situ cytokine modulation of Langerhans cell phenotype in inflamed skin. Furthermore, they indicate that epidermal DCs in psoriasis and other cutaneous inflammatory diseases express molecules that are known to be crucial for Langerhans cell-driven T-cell activation in vitro.     

Immunolocalization of adhesion molecules in psoriatic arthritis, psoriatic and normal skin

Adhesion molecule expression in synovial membrane obtained from patients with psoriatic arthritis (PA) has previously been compared with rheumatoid arthritis (RA). Although expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) was similar in both psoriatic and rheumatoid synovium, in contrast, little or no endothelial leucocyte adhesion molecule-1 (ELAM-1) was observed in psoriatic synovium. In the present study, the expression of ICAM-1. ELAM-1 and VCAM-1 was examined in the involved and uninvolved skin from patients with PA (n= 15), patients with psoriasis (Ps) but no arthritis (n= 5) and in normal skin (n= 4). ICAM-1 was intensely expressed on endothelium and keratinocytes of involved skin from patients with Ps with or without arthritis. There was constitutive expression of ICAM-1 on endothelium only in uninvolved and normal skin. In contrast, ELAM-1 expression was restricted to endothelial cells; it was widespread and intense in involved skin, but was minimal in uninvolved and normal skin. VCAM-1 was expressed on endothelium, and also on some dendritic cells in involved psoriatic skin. There was minimal VCAM-1 staining on endothelial cells in uninvolved and normal skin. In conclusion, in involved psoriatic skin from patients with and without arthritis ICAM-1, ELAM-1 and VCAM-1 expression is up-regulated on vascular endothelium, and ICAM-1 is expressed on keratinocytes. However, ELAM-1 and VCAM-1 expression seen in dermal vessels is not found in psoriatic synovial vessels. These differences suggest a mechanism for controlling cellular traffic in Ps and in PA.     

Functional CD86 (B7-2/B70) is predominantly expressed on Langerhans cells in atopic dermatitis

Recently, we reported the functional expression of CD86 on cultured human Langerhans cells derived from normal epidermis. In the present study, we investigated the expression and function of co-stimulatory molecules in the pathogenesis of atopic dermatitis. In immunohistochemical analysis, CD80 and/or CD86 were detected on dendritic-shaped cells not only in the epidermis but also in the dermis in the inflammatory lesions of atopic dermatitis (n = 12). CD80 was expressed in only five cases (42%), while CD86 was expressed in all cases (100%). These molecules were not detected in normal control subjects (n = 8). In non-lesional skin of atopic dermatitis (n = 4). CD86 but not CD80 was detected in one case. CD86 was preferentially induced on dendritic-shaped cells in positive patch test sites to Dermatophagoides pteronyssinus or house dust allergen in atopic dermatitis (n = 4). The CD80- or CD86-positive cells were confirmed as Langerhans cells by double immunostaining using anti-CD1a monoclonal antibody. Neither CD86 over that CD80 was detected n keratinocytes. Similar results of the stronger expression of CD86 over that of CD80 were obtained from psoriasis vulgaris (n = 11) and from contact dermatitis (n=7), although CD86 was expressed only in 57% of the contact dermatitis cases. The percentage of Langerhans cells positive for CD86 was higher than for CD80, i.e. 48% compared with 9%, respectively, in the epidermis of lesional skin of atopic dermatitis (n=8). The expression rate of these molecules on Langerhans cells increased in the dermis. To investigate the function of co-stimulatory molecules on Langerhans cells in atopic dermatitis, we conducted an inhibition test with antibodies. Anti-CD86 monoclonal antibody almost completely nhibited T-cell proliferation stimulated with crude extract of D. pteronyssinus in the presence of epidermal cells as antigen-presenting cells, whereas anti-CD80 monoclonal antibody produced less of an inhibitory effect. These data indicate that CD86 expressed on Langerhans cells may play an important part in the pathogenesis of atopic dermatitis.for Investigative Dermatology. Washington, DC (1–5 May 1996).     

Adhesion molecules and IL-1 costimulate T lymphocytes in the autologous MECLR in psoriasis

Membrane molecules such as CD36 (OKM5), intercellular adhesion molecule-1 (ICAM-1, CD54), gamma interferon-induced protein 10 (γ-IP10) and IL-1 are induced and/or upregulated in psoriatic epidermis. These molecules have important accessory, trafficking or signalling functions in the immune system and also play a role in the pathophysiology of psoriasis. The relevance of adhesion molecules, CD36 and epidermal IL-1 in psoriasis was studied in vitro in the autologous mixed epidermal cell-T lymphocyte reaction (MECLR). Their level of expression was quantitated in epidermal cell suspensions (ECS) from patients with psoriasis and their function was assessed by blocking with specific mAbs and antisera or by depleting CD36⁺ cells from the ECS prior to the MECLR. ECS from psoriatic lesions contained increased numbers of CD36⁺ (23±12%), ICAM-1⁺ (31±14%) and IL-1⁺ (57±21%) cells. The autologous MECLR was inhibited in saaples from all patients by mAb to CD2 (LFA-2), CD11a (LFA-1α), CD18 (LFA-1β), ICAM-1, CD58 (LFA-3) and an antiserum to IL-1β. Thus, adhesion molecules facilitate inflammation in psoriasis not only via adhesion and recruitment of T lymphocyte in psoriatic lesions, but also via activation of T cells. Furthermore CD36 molecules on psoriatic epidermal cells do not costimulate autologous T lymphocytes in psoriasis. The observed costimulatory function of IL-1β in the MECLR emphasizes its relevance in psoriasis.     

Effect of UVB 311 nm irradiation on normal human skin

Ultraviolet radiation B (UVB) on the skin induces erythema, inflammation and modifications of the immune system. These changes have been reported after excessive short-term or long-term exposure to broad spectrum UVB. In this study, we examined the effects of local repetitive UVB irradiation of 311 nm wavelength on the skin of seven young volunteers. Skin biopsies were taken before and after UVB irradiation, and we immunohistochemically analyzed the expression of CD1a and HLA-DR antigens of Langerhans cells (LC), the possible infiltration of dermis/epidermis by CD11b macrophages, the modifications or the induction of intercellular adhesion molecule-1 (ICAM-1), E-selectin and vascular cell adhesion molecule-1 (VCAM-1) involved in the binding of leukocytes to the endothelial surface and the development of perivascular infiltrates of LFA-1⁺ mononuclear cells. We also determined the expression of substance P receptors (SPR) using biotinylated substance P (SPB). Exposure of UVB 311 nm induced a drastic reduction of CD1a⁺ cells and a moderate increase of HLA-DR⁺ dendritic cells in the epidermis without infiltration by CD11b macrophages. An increase of the binding of SPB to upper layer epidermal cells was noted in five of seven biopsies. In the dermis, vessel-associated ICAM-1 expression increased and an induction of E-selectin occurred on nearly 20 to 40% of endothelial cells, but VCAM-1 expression remained undetectable. The percentage of LFA-1⁺ cells did not change significantly after irradiation. These observations may be compatible with a selective role of UVB 311 nm on the skin immune response.     

Malignant T cells in cutaneous T‐cell lymphoma lesions contain decreased levels of the antiapoptotic protein Ku70

Background Malignant T cells in primary cutaneous T‐cell lymphoma (CTCL) are genetically unstable and exhibit prolonged lifespans potentially explained by dysregulation of apoptosis, yet are responsive to apoptosis‐inducing therapies. The heterodimeric protein Ku70/80 is known to play a role in DNA repair (Ku70 and Ku80) and inhibition of apoptosis (Ku70 only). Objectives To investigate the expression of Ku70/80 in CD3+ T cells derived from skin and blood in patients with CTCL and normal samples, as well as benign dermatoses. Methods Normal (n = 10), CTCL (n = 9) and benign dermatoses (n = 13) skin samples were stained for confocal imaging of Ku70/80 and CD3 and analysed using imaging software. Circulating CD4+ T cells in normal and CTCL peripheral blood were analysed by flow cytometry and Western blot for Ku70/80 expression (n = 6). Results Ku70 and Ku80 were significantly diminished in T cells of CTCL lesions relative to T cells of control skin. Decreased T‐cell Ku70 expression was not a feature of the benign dermatoses psoriasis and contact dermatitis, suggesting that loss of Ku70/80 in CTCL is not simply the result of cutaneous inflammation. Reduced Ku70 was also noted in circulating CD4+ T cells in patients with CTCL with peripheral blood involvement. Conclusions Deficient expression or lack of Ku70/80 may result in genomic instability and play a role in tumorigenesis, as well as account for the increased susceptibility of malignant T cells to apoptosis‐inducing treatment modalities in the setting of intrinsic resistance to apoptosis.     

A Case of Chronic GVHD Following Bone Marrow Transplantation from a Phenotypically HLA-Matched Unrelated Donor

A 45-year-old male with chronic myelocytic leukemia who received a bone marrow transplantation from a phenotypically HLA-matched unrelated donor developed chronic GVHD on day 100 post transplantation. He developed a slight fever, malaise, hepatic dysfunction and extensive itchy erythema with scaling over his entire body. The inflammatory skin lesion developed into erythroderma in about two weeks. H&E staining of a skin biopsy revealed eosinophilic bodies and a lymphocytic infiltration in the dermis and epidermis, which were compatible with the early phases of chronic GVHD. Immunohistochemistry revealed that keratinocytes expressed dense HLA-DR and ICAM-1 epitopes. Langerhans cells (CD1a⁺ cells) had disappeared from the epidermis. Many T cells (CD3⁺ cells) had migrated into the epidermis as well as into the reticular dermis. The majority of the T cells in the epidermis were CD8⁺ cells, while almost all the T cells in the dermis were CD4⁺ cells. These immunohistochemical features were similar to those previously reported for acute cutaneous GVHD. Despite the corticosteroid therapy, the eruptions did not disappear. The patient was then treated with whole body bath-methoxsalen (Oxsoralen®) plus ultraviolet A (UVA). The bath-psoralen plus UVA therapy was effective in this patient.     

Mast cells of psoriatic and atopic dermatitis skin are positive for TNF-α and their degranulation is associated with expression of ICAM-1 in the epidermis

Abstract The release of cytokines from cutaneous cells may be of major importance in the initiation and development of many inflammatory skin disorders. For example, tumor necrosis factor-alpha (TNF-α), which in healthy skin is found preformed only in mast cells, is able to induce the expression of several adhesion molecules including intercellular adhesion molecule-1 (ICAM-1). Increased expression of ICAM-1 occurs in keratinocytes in lesional skin of psoriasis and atopic dermatitis (AD) and it is considered to be an important initiator of leucocyte/keratinocyte interactions in skin inflammation. We counted the mast cells showing TNF-α immunoreactivity using a double-staining method in nonlesional and lesional skin sections from 12 patients with AD and 12 patients with psoriasis. The percentage of TNF-α⁺ mast cells in lesional and nonlesional AD skin was 36 ± 22% and 21 ± 15% (P < 0.018, paired t-test), respectively, and in psoriatic skin was 16 ± 25% and 15 ± 15%, respectively (P < 0.89, paired t-test). We also cultured whole skin biopsies taken from the healthy-looking skin of psoriatic and AD patients in the presence of mast cell degranulator compound 48/80, which resulted in focal expression of ICAM-1 in the epidermis. In cultured keratinocytes, both histamine and an extract of a human mast-cell line (HMC-1) induced ICAM-1 immunostaining only in occasional cells, but the combination of histamine and the HMC-1 extract resulted in intense ICAM-1 staining in numerous cells. This enhancement of ICAM-1 staining was abolished by preincubation of the HMC-1 extract with anti-TNF-α antibody. These results suggest that the degranulation of mast cells induces the expression of ICAM-1 in keratinocytes probably via TNF-α and histamine. Received: 8 August 1997     

Skewed distribution of natural killer cells in psoriasis skin lesions

Psoriasis is a hyper‐proliferative disease of the skin in which immunological mechanisms play a direct pathogenetic role. There have been limited studies of natural killer (NK) cells in psoriasis. The aim of this study was to examine the phenotype of NK cells in skin biopsies and peripheral blood mononuclear cells from patients with psoriasis and healthy controls. CD56⁺CD16^? and CD56⁺CD16⁺ NK cells were isolated from lesional skin, unaffected skin and PBMC of psoriasis patients, and normal skin and PBMC from healthy controls. The expression of CD57, NKG2A and NKG2C was assessed by flow cytometry. NK cells in psoriasis skin lesions were skewed in their expression of CD57, a marker of NK cell maturity, with CD57 expression significantly reduced and NKG2A expression increased on NK cells in lesional and unaffected skin compared to controls. These data suggest that in this patient cohort, NK cells could be isolated from psoriasis lesions and exhibit an immature phenotype.     

Immunohistochemical Studies of Infiltrating Cells in Early and Chronic Lesions of Psoriasis

The expression of surface antigens on infiltrating cells, epidermal keratinocytes, and dendritic cells in biopsy specimens from 31 patients with psoriasis was examined immunohistochemically. The specimens were divided into early-phase and chronic-phase groups and then examined in a double blind manner. Among the infiltrating cells in the epidermis, CD4-positive cells were dominant in the early phase; CD8-positive cells were dominant in the chronic phase, resulting in a markedly decreased CD4/CD8 ratio in the latter. On the other hand, among the infiltrating cells in the dermal papillae, CD4-positive cells were dominant in both the early and chronic phases; both CD4-positive and CD8-positive cells were more dominant in the chronic phase than in the early one. However, the CD4/CD8 ratios were decreased in both the dermal papillae and the epidermis in the chronic phase. CD1-positive dendritic cells (probably Langerhans cells) were more numerous in the chronic phase than in the early phase. There were no significant differences between the early and chronic phases with regard to the expression of HLA-DR and HLA-DQ antigens on the infiltrating cells. However, the HLA-DR antigens and ICAM-1 (intercellular adhesion molecule-1) were more strongly expressed on epidermal keratinocytes in the chronic phase than in the early phase. LFA-1α (lymphocyte function-associated antigen-1α)-positive cells were also significantly more numerous in the chronic phase than in the early one, consistent with the expression of HLA-DR antigens and ICAM-1 on keratinocytes mentioned above. On the other hand, VLA-4 (integrin α₄β₁) positive cells were expressed more abundantly in the epidermis in the early phase than in the chronic phase. These results suggest, first, that the chronic phase of psoriasis is as immunologically active as or more active than the early phase. Second, CD4-positive T cells are more important than CD8-positive T cells in the early phase of psoriasis; CD8-positive rather than CD4-positive T cells are more important in the chronic phase. Third, the LFA-1/ICAM-1 pathway may play an important role with regard to cell adhesion of the infiltrating cells in the psoriatic lesions in disease exacerbation or prolongation, whereas the VLA-4/VCAM-1 (vascular cell adhesion molecule-1) pathway may be more important in disease onset.     

Serum soluble CD26 levels: diagnostic efficiency for atopic dermatitis,cutaneous T‐cell lymphoma and psoriasis in combination with serum thymus and activation‐regulated chemokine levels

Background CD26 is a multifunctional type II transmembrane glycoprotein, which also exists as a secreted isoform, soluble CD26 (sCD26). The CD26 expression on circulating T cells is decreased in some skin diseases such as cutaneous T‐cell lymphoma (CTCL) and psoriasis. It remains to be determined whether sCD26 can be used as a marker of skin diseases or not. Objective To investigate utility of sCD26 as a diagnostic marker of skin diseases in combination with thymus and activation‐regulated chemokine (TARC). Methods Serum sCD26 levels were measured using enzyme‐linked immunosorbent assay in 130 participants including 32 patients with atopic dermatitis (AD); 45 patients with CTCL; 26 patients with psoriasis; and 27 healthy controls. Results Serum sCD26 levels in patients with CTCL and psoriasis (162.1 ± 80.2 ng/mL and 125.4 ± 82.1 ng/mL respectively) were significantly lower than those of healthy controls (392.6 ± 198.7 ng/mL; P < 0.01 and 0.01 respectively). In patients with CTCL, serum sCD26 levels of patients with advanced stage were 135.0 ± 51.5 ng/mL and they were significantly lower than those with early stage (193.1 ± 96.0 ng/mL; P < 0.05). When we used serum sCD26 and TARC levels for diagnostic criteria, sensitivity, specificity, positive predictive value and negative predictive value for AD, CTCL and psoriasis were 65.2–73.7%, 81.4–97.6%, 65.2–94.4%, and 81.4–88.9% respectively. Conclusion Serum sCD26 levels, combined with serum TARC levels, are helpful in diagnosis of AD, CTCL and psoriasis.     

蕈样肉芽肿与扁平苔藓、银屑病浸润细胞的免疫组化比较

目的 探讨免疫表型对蕈样肉芽肿与扁平苔藓、银屑病鉴别诊断的意义.方法 应用ABC免疫组化技术检测15例蕈样肉芽肿,17例银屑病和17例扁平苔藓,6例正常人皮肤的CD1a、CD4、CD8、ICAM-1、LFA-1、HLA-DR(树枝状细胞)、CD30和CD7的表达情况.结果 蕈样肉芽肿表皮CD1a,CD30,ICAM-1(单一核细胞P<0.001,树枝状细胞P<0.01)的阳性细胞密度明显高于扁平苔藓、银屑病、正常人皮肤.蕈样肉芽肿表皮CD4,CD8,HLA-DR的阳性细胞密度明显高于扁平苔藓.蕈样肉芽肿真皮中CD1a阳性细胞的线性密度(P<0.01),真皮内ICAM-1和LFA-1阳性细胞百分比亦较扁平苔藓增多(P<0.05).蕈样肉芽肿表皮CD7阳性细胞与扁平苔藓、银屑病比较差异无统计学意义.银屑病和扁平苔鲜真皮内CD7阳性细胞百分比高于蕈样肉芽肿和正常人皮肤.结论 蕈样肉芽肿和扁平苔藓、银屑病皮损CD1a、CD4、CD8、ICAM-1、LFA-1、HLA-DR、CD30和CD7免疫表型有差异,其结果可为探讨发病机制提供线索.