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  • 1
    Electronic Resource
    Electronic Resource
    Evidence for a role of type I interferons in the pathogenesis of dermatomyositis (2005)
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 153 (2005), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2133.2005.06786.x
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  • 2
    Electronic Resource
    Electronic Resource
    Lymphocytopenia in lupus erythematosus: close in vivo association to autoantibodies targeting nuclear antigens (2004)
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 150 (2004), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background  Leukopenia and lymphopenia are typical features of lupus erythematosus (LE) and correlate with elevated disease activity and higher grades of systemic involvement. Antilymphocyte antibodies are regarded as the most likely rationale for the decreased cell numbers; however, their relevance has not been confirmed so far.Objectives  Previous investigations at our department have shown a significant correlation between diminished lymphocyte numbers and the presence of antinuclear antibodies (ANA). We wanted to achieve a better understanding of this phenomenon.Methods  We performed a detailed analysis of autoantibodies and peripheral leucocyte subsets in 82 patients with different subtypes of LE. Leucocyte subsets were measured using flow cytometry (FACScanTM; Becton Dickinson, Franklin Lakes, NJ, U.S.A.); autoantibodies were detected by indirect immunofluorescence and by enzyme-linked immunosorbent assay.Results  A significant association (P 〈 0·05) between specific antibodies targeting nuclear antigens (SSA/Ro-52, SSB/La, snRNPs) and lymphocytopenia was found.Conclusions  We suppose that some of these autoantibodies might have an antilymphocyte effect. Apoptosis induction by specific antinuclear antibodies has already been described earlier, but to the best of our knowledge this is the first study presenting a strong indication of a possible interaction between these antibodies and lymphocyte subsets in vivo.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2133.2004.05848.x
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  • 3
    Electronic Resource
    Electronic Resource
    Efficacy and safety of methotrexate in recalcitrant cutaneous lupus erythematosus: results of a retrospective study in 43 patients (2005)
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 153 (2005), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background  The therapy of cutaneous lupus erythematosus (CLE) is often challenging, especially in patients resistant to topical treatment and established first-line systemic drugs such as antimalarials. Systemic corticosteroids are effective, but their use is limited due to well-known side-effects, especially in long-term treatment. In recent years several other immunosuppressive agents have been successfully applied in CLE. However, there are no large studies or explicit guidelines on the use of these drugs in CLE.Objectives  To perform a retrospective investigation of the efficacy of low-dose methotrexate (MTX) in the treatment of CLE.Methods  One hundred and thirty-nine patients with CLE were seen at our department between 2001 and 2003, of whom 43 patients required low-dose MTX. All had histologically confirmed CLE lesions. Clinical data including disease activity, additional treatment, laboratory parameters and side-effects were recorded carefully at the time of presentation. Statistical analyses were performed by paired nonparametric Wilcoxon test and Student's t-test using SPSS 11 software.Results  MTX led to a highly significant (P 〈 0·01) decline in disease activity. An improvement of the cutaneous lesions was recorded in nearly all patients treated with MTX (42 of 43; 98%). Severe side-effects necessitating discontinuation of MTX treatment were recorded in seven patients (16%), which quickly resolved when MTX was discontinued. Life-threatening complications were not observed. Intravenous application was tolerated better than oral administration. Interestingly, we observed a significant increase in circulating lymphocyte numbers in patients with lymphopenia (〈 1·0 × 109 cells L−1) prior to MTX treatment.Conclusions  Our study supports earlier findings reporting the efficacy of low-dose MTX in CLE lesions, particularly in recalcitrant clinical courses. MTX treatment appears to be safe if patients are carefully selected and monitored, with particular attention to side-effects and contraindications.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2133.2005.06552.x
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  • 4
    Electronic Resource
    Electronic Resource
    Absence of CD26 expression on skin-homing CLA+ CD4+ T lymphocytes in peripheral blood is a highly sensitive marker for early diagnosis and therapeutic monitoring of patients with Sézary syndrome (2005)
    Oxford, UK : Blackwell Science Ltd
    Clinical and experimental dermatology 30 (2005), S. 0 
    Details
    ISSN: 1365-2230
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Patients with Sézary syndrome (SS) show clonal expansion in the peripheral blood of skin-homing CD4+ T-helper cells expressing cutaneous lymphocyte antigen (CLA). However, an increase of CLA+ CD4+ T cells can also be observed in various inflammatory dermatoses. To facilitate early diagnosis and therapeutic monitoring of SS using flow cytometry, we evaluated the expression of CD7 and CD26 on the CLA+ CD4+ lymphocyte subset. Peripheral lymphocytes from 7 patients with SS, 16 patients with mycosis fungoides (MF) and 11 healthy controls were analysed by flow cytometry for the expression of CD4, CD7, CD26, CLA and CCR4. In addition, a longitudinal study was performed over 16 months in two patients with SS. Absence of CD7 and CD26 on CLA+ CD4+ T cells was highly specific for SS. Importantly, the absence of CD26 on CLA+ CD4+ T cells was very sensitive for SS, at 100% in our patient cohort. The number of CD26− CLA+ CD4+ T cells closely correlated with therapeutic interventions in the longitudinal analysis of two patients over more than 1 year. We conclude that the absence of CD26 expression on skin-homing CLA+ CD4+ T-helper cells is a very sensitive and highly specific parameter for early diagnosis and therapeutic monitoring of patients with SS.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2230.2005.01904.x
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  • 5
    Electronic Resource
    Electronic Resource
    Successful treatment of recalcitrant Wegener's granulomatosis of the skin with tacrolimus (PrografTM) (2004)
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 151 (2004), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2133.2004.06187.x
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  • 6
    Electronic Resource
    Electronic Resource
    Circulating clonal CLA+ and CD4+ T cells in Sézary syndrome express the skin-homing chemokine receptors CCR4 and CCR10 as well as the lymph node-homing chemokine receptor CCR7 (2005)
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 152 (2005), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background  Adhesion molecules and chemokine receptors are involved in tissue-specific homing of T cells to the skin and play an important role in the pathophysiology of cutaneous lymphoma. It has recently been reported that the chemokine CCL27 expressed by keratinocytes attracts lymphocytes bearing the chemokine receptor CCR10.Objectives  To investigate the expression of CCR4, CCR7 and CCR10 on skin-homing CLA+ and CD4+ T cells in the peripheral blood of patients with Sézary syndrome (SS), a rare leukaemic variant of cutaneous T-cell lymphoma.Methods  Lymphocytes from five patients with SS, six patients with mycosis fungoides and four healthy volunteers were isolated and analysed using flow cytometry. Additionally, the T-cell receptor (TCR)-Vβ CDR3 regions were cloned and sequenced in two patients.Results  We found that CCR4 is expressed on almost all CLA+ and CD4+ memory T cells. Using monoclonal antibodies specific for single TCR-Vβ chains we identified malignant T cells in four patients with SS. Importantly, we found that most but not all malignant Sézary cells expressed the skin-homing chemokine receptor CCR10. Additionally, we found that a significant proportion of these cells also expressed the lymph node-homing chemokine receptor CCR7.Conclusions  Our results support the concept that chemokine receptors play an important role in the pathophysiology of SS and suggest that the malignant clone may represent an expansion of skin-homing cutaneous ‘central’ memory T cells in the peripheral blood of these patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2133.2004.06325.x
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  • 7
    Electronic Resource
    Electronic Resource
    Scarring skin lesions of discoid lupus erythematosus are characterized by high numbers of skin-homing cytotoxic lymphocytes associated with strong expression of the type I interferon-induced protein MxA (2005)
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 153 (2005), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background  Infiltrating T lymphocytes are considered to play a major pathological role in skin lesions of cutaneous lupus erythematosus (CLE), a cutaneous autoimmune disease of unknown aetiology. Earlier histological studies revealed that the inflammatory infiltrate in CLE skin lesions is predominantly composed of T lymphocytes, with a slight predominance of CD4+ over CD8+ T cells, but failed to explain the development of scarring skin lesions, characteristic for chronic discoid lupus erythematosus (CDLE). Because recent investigations have highlighted the relevance of cytotoxic lymphocytes in autoimmune tissue destruction, we hypothesized that the scarring CDLE lesions might be caused by cytotoxic T lymphocytes.Objectives  To analyse skin biopsies of 15 patients with CLE [10 female, five male; localized CDLE (lCDLE), n = 5; disseminated CDLE (dCDLE), n = 5, subacute CLE (SCLE), n = 5] and five control biopsies taken from healthy controls and to characterize the inflammatory infiltrate.Methods  We used immunohistochemistry, including staining for the cytotoxic molecule granzyme B, the skin-homing molecule cutaneous lymphocyte antigen (CLA) and the protein MxA, which is specifically induced by type I interferons (IFNs).Results  We found a strong coexpression of granzyme B and CLA on lesional lymphocytes of patients with scarring lCDLE and dCDLE, which was significantly enhanced when compared with nonscarring SCLE and healthy controls. The increased expression of granzyme B was closely associated with the lesional expression of the type I IFN-induced protein MxA.Conclusions  Our results provide evidence that type I IFNs and potentially autoreactive cytotoxic lymphocytes targeting adnexal structures are highly associated with scarring lupus erythematosus lesions and might be responsible for their scarring character.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2133.2005.06784.x
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  • 8
    Electronic Resource
    Electronic Resource
    Induction of dendritic cell maturation and modulation of dendritic cell-induced immune responses by prostaglandins (2000)
    Springer
    Archives of dermatological research 292 (2000), S. 437-445 
    Details
    ISSN: 1432-069X
    Keywords: Key words Prostaglandins ; Dendritic cell ; T cell ¶immunity ; Th1 response
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Dendritic cells (DC) are the most potent antigen-presenting cells of the immune system. In this study we investigated the effects of various prostaglandins (PG) on the stimulatory capacity of DC. DC were generated from peripheral progenitor cells in the presence of IL-4 and GM-CSF and stimulated with ¶IL-1, IL-6 and TNF-· on day 7. Simultaneously, PG (PGD2, PGE1, PGE2, PGF2alpha, PGI2) were added at various concentrations (10–5 to 10–9 M) on day 7. In all experiments, PGE2 had the most potent influence on the maturation of the DC, followed by other PG in the order PGE1〉PGD2〉PGF2alpha〉PGI2. In addition, the expression of the surface molecules CD40, CD54, CD58, CD80, CD83, CD86 and the MHC class II molecules was upregulated after stimulation with PG. Analysis of DC supernatants after treatment with PG demonstrated significantly higher amounts of the proinflammatory cytokines IL-1‚, IL-6, TNF-·, and IL-12. Addition of PG to DC induced a markedly enhanced proliferation of both naive and activated CD4+ and CD8+ T cells in alloantigen-induced MLR assays. Assessment of coculture supernatants after restimulation revealed significantly higher amounts of the Th1-cytokines IL-2 and IFN-Á and only minimal amounts of IL-4 compared to control cells. No production of IL-10 was observed. The effects of PG on the maturation of DC and enhanced T-cell proliferation could be mimicked by db-cAMP and forskolin, indicating that they were due to elevated cAMP levels. Collectively, our data show that members of the PG family promote the differentiation of DC and enhance their capacity to induce a Th1 immune response.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004030000159
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