312-nanometer ultraviolet B light (narrow-band UVB) induces apoptosis of T cells within psoriatic lesions.

Narrow-band (312 nm) ultraviolet B light (UVB) is a new form of therapy for psoriasis, but its mechanism of action is unknown. In a bilateral comparison clinical study, daily exposure of psoriatic plaques to broad-band UVB (290-320 nm) or 312-nm UVB depleted T cells from the epidermis and dermis of psoriatic lesions. However, 312-nm UVB was significantly more depleting in both tissue compartments. To characterize the mechanism of T cell depletion, assays for T cell apoptosis were performed on T cells derived from UVB-irradiated skin in vivo and on T cells irradiated in vitro with 312-nm UVB. Apoptosis was induced in T cells exposed to 50-100 mJ/cm2 of 312-nm UVB in vitro, as measured by increased binding of fluorescein isothiocyanate (FITC)-Annexin V to CD3(+) cells and by characteristic cell size/granularity changes measured by cytometry. In vivo exposure of psoriatic skin lesions to 312-nm UVB for 1-2 wk also induced apoptosis in T cells as assessed by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) reaction in tissue sections, by binding of FITC-Annexin V to CD3(+) T cells contained in epidermal cell suspensions, and by detection of apoptosis-related size shifts of CD3(+) cells. Induction of T cell apoptosis could be the main mechanism by which 312-nm UVB resolves psoriasis skin lesions.

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.

Cutaneous B-cell lymphoma: important diagnostic tools.

Primary cutaneous B-cell lymphomas (PCBCL) represent a heterogeneous group of lymphoproliferative disorders characterized by clonal proliferation of neoplastic B-cells in the skin. The recent joint World Health Organization (WHO) and European Organization for the Research and Treatment of Cancer (EORTC) classification recognizes three major subgroups of PCBCL: primary cutaneous follicle center lymphoma (PCFCL), primary cutaneous marginal zone B-cell lymphoma (PCMZL) and primary cutaneous large B-cell lymphoma, leg type (PCLBCL-LT). Recent advances in the field and the availability of new methodological tools have greatly enhanced our insights into the biology of cutaneous B-cell lymphomas and allow a more precise definition of these entities. Considerable progress over the past decade has led to significantly improved diagnostic accuracy allowing earlier diagnosis, targeted strategies and improved therapeutic results in the management of primary cutaneous B-cell lymphomas. This review presents an overview of primary cutaneous B-cell lymphomas with an emphasis on the proper incorporation of current and emerging diagnostic tools into the work-up and classification of this group of unique malignancies.

Breast implant-associated anaplastic large cell lymphoma: A review and assessment of cutaneous manifestations.

One newly recognized form of T-cell lymphoma is breast implant-associated anaplastic large cell lymphoma (biALCL), which appears in close proximity to breast implants. The number of reported cases of biALCL is increasing and warrants careful attention by clinicians to more effectively diagnose and treat affected individuals. As pertinent to dermatologists, the objective of this paper is to present the associated cutaneous features of this clinical entity along with the pathogenesis, management, and clinical outcomes. biALCL is a T-cell lymphoma in which malignant T-cells are characterized by large pleomorphic and anaplastic morphology and immunoreactivity for CD30, similar to primary cutaneous anaplastic large cell lymphomas (pcALCL). It has a favorable clinical outcome like nonimplant-associated pcALCL and involves the fibrous capsule around the implant, which creates an immunologically privileged site with a peri-implant effusion (seroma). More rare presentations are of a solitary mass. Appropriate management of biALCL is the complete surgical removal of the implant and total capsulectomy. Dermatologists should be aware of the occurrence of this entity in patients who have breast implants because patients may present specifically for breast-related cutaneous findings or have incidental cutaneous changes noted during a skin examination. The recognition and timely diagnosis of biALCL is critical to prevent progression to more advanced disease, ensure adequate treatment with removal of the implant, and avoid unnecessary aggressive systemic chemotherapy.

[Connection between Helicobacter pylori infection and chronic gastrointestinal urticaria]. / A Helicobacter pylori fertözés és a gastrointestinalis krónikus urticaria összefüggésének vizsgálata.

Chronic urticaria is a disease of unknown etiology. One type of the disease is accompanied by gastrointestinal complaints. The aim of the present study was to determine the prevalence of Helicobacter pylori (H. pylori) infection in patients with chronic urticaria, and measure the effectiveness of eradication of HP on the skin disease. Patients with chronic urticaria of other origin were excluded from the study. Forty patients out of 95 studied fulfilled the criteria of gastrointestinal urticaria. H. pylori was measured both by measuring H. pylori-specific IgG in the serum and by direct staining of biopsy specimen taken upon endoscopy prior to and after the treatment. Seventeen patients out of 40 with gastrointestinal urticaria were H. pylori positive which incidence (43%) is not higher than that of the age matched healthy population in Hungary. H. pylori positive patients were treated with amoxycillin (4 x 500 mg/die), bismuth subsalicilate (3 x 512 mg/die) and metronidazole (2 x 500 mg/die) for two weeks, respectively, and those remaining positive were treated by omeprazole (2 x 20 mg/die) and amoxycillin for additional two weeks. Eradication of HP infection was successful in all patients. Follow-up was conducted from 6-18 months for urticaria (frequency, duration) and antihistamine drug requirement. Chronic urticaria did not disappeared after the eradication of H. pylori, but there was a significant reduction both in frequency, duration of urticaria and the need for antihistamine therapy after eradication of H. pylori. It was concluded that H. pylorilinfection has no effect on the course of chronic urticaria. Reduction in frequency of urticaria symptoms and reduction of antihistamine requirement is partly due to the natural course of the disease and likely due to the altered bacterial flora of the gut following the combined antibiotic treatment.

CD69, HLA-DR and the IL-2R identify persistently activated T cells in psoriasis vulgaris lesional skin: blood and skin comparisons by flow cytometry.

Many lymphocyte-activation-associated molecules are observed by immunohistochemistry in psoriasis vulgaris lesional skin. Non-T cells in lesional skin also express these molecules. We quantitatively measured the number of T cells expressing cell surface activation-associated molecules (CD69, CD25, CD122, HLA-DR) and co-stimulatory molecules (CD28, CTLA-4, CD80, CD86), including a Type 2 T cell marker (CD30) and CD11b, by flow cytometry of skin and peripheral blood. T cells in single cell suspensions of psoriatic lesional-epidermis-expressed HLA-DR (86%), CD69 (59%), CD25 (55%), CD122 (44%), and CD28 (91%). Dermal T cells showed similar percentages except for CD69 (17%). CD69 was found directly in lesional skin biopsies by immunohistochemistry. Both CD4 and CD8 subsets from lesional skin contained large populations of CD25+ cells with a bias towards CD8 activation in the epidermis and towards CD4 activation in the dermis. CD86, CD80, CTLA-4, CD30 and CD11b were expressed by less than 23% of the T cell populations from both the epidermis and dermis. CD30+CD4+ cells were found two-fold over CD8+ T cells. These results show that the majority of lesional lymphocytes are persistently activated. We also found the majority of Type 2 associated markers primarily on the CD4+ epidermal T cell population. Psoriatic blood contained elevated levels of T cells expressing CD25, primarily within the CD8+ subset. Thus the majority of lesional T cells expressed the three primary activation markers, while psoriatic blood T cells were distinguished by an increase in CD25, specifically within the CTL population.

Neutrophils, monocytes, and dendritic cells express the same specialized form of PSGL-1 as do skin-homing memory T cells: cutaneous lymphocyte antigen.

Memory T cells in inflamed skin express the cutaneous lymphocyte-associated antigen (CLA), a glycosylated epitope defined by the mAb HECA-452. We previously reported that on T cells, CLA occurs almost exclusively on the protein backbone of P-selectin glycoprotein ligand-1 (PSGL-1). T cells exhibiting the CLA isoform of PSGL-1 can tether and roll on both E- and P-selectin, while T cells expressing PSGL-1 without the CLA epitope do not bind E-selectin, though they may bind P-selectin. We show here that circulating neutrophils and monocytes, and cultured blood dendritic cells, also express CLA almost entirely as an isoform of PSGL-1. These cells all tether and roll on both E- and P-selectin. A chimeric fusion protein incorporating the 19 N-terminal amino acids of mature PSGL-1 exhibited HECA-452 immunoreactivity and supported rolling of CHO cells expressing either E- or P-selectin. These findings indicate a site for the CLA modification within the distal tip of PSGL-1, previously shown to be critical for P-selectin binding and to mediate some, but not all, of the E-selectin binding of PSGL-1. We hypothesize that the types of circulating leukocytes discussed above all use CLA/PSGL-1 to tether and roll on E- and P-selectin along the vascular endothelium.