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1.
J Invest Dermatol ; 142(3 Pt B): 804-810, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34538423

RESUMO

T cells are key drivers of autoimmunity in numerous noncommunicable inflammatory skin diseases by directly harming host tissue or through helping B cells in producing autoantibodies. Technological advances have contributed to identifying autoantigens, the Holy Grail of autoimmunity, in many inflammatory disorders of the skin. Novel therapeutic approaches such as chimeric (auto)antibody receptor T cells are a milestone on the way to finding individualized, well-tolerated, targeted therapies. This review summarizes the current knowledge on pathogenesis, immune response pattern‒related ontology, diagnostic approaches, and treatment options of autoimmune skin diseases.

2.
J Invest Dermatol ; 142(3 Pt A): 549-558.e6, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34480891

RESUMO

Reactivation of latent Epstein‒Barr virus (EBV) and/or Cytomegalovirus (CMV) infection is a dreaded complication in immunocompromised patients receiving hematopoietic stem cell transplantation. Evidence is sparse on whether subclinical reactivation of viral infection may also be of clinical relevance in dermatological patients. We screened patients (N = 206) suffering from chronic skin diseases for subclinical reactivation of EBV and CMV infection. We found that immunocompromised patients with therapy-refractory chronic skin diseases showed higher rates of subclinical reactivation of CMV and EBV infection (6.7% vs. 0% for EBV and 16.7% vs. 5.6% for CMV) and a higher prevalence of virus-specific DNA in skin tissue (30.8% vs. 0% for EBV and 21.4% vs. 0% for CMV) than nonimmunocompromised patients with chronic skin diseases. T cells isolated from lesional skin exhibited up to 14-fold increased proliferation with production of T helper type 1 and T helper type 17 cytokines on stimulation with viral proteins, providing evidence for possible aggravation of the underlying skin diseases by viral infection. Improvement of skin lesions in patients with reactivation of CMV infection (n = 4) was observed on antiviral treatment. Our data suggest that subclinical reactivation of EBV and/or CMV infection is an under-recognized condition in the dermatological patient population with chronic skin diseases.

3.
Cells ; 10(8)2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34440863

RESUMO

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease primarily affecting apocrine gland-rich areas of the body. It is a multifactorial disease in which genetic and environmental factors play a key role. The primary defect in HS pathophysiology involves follicular occlusion of the folliculopilosebaceous unit, followed by follicular rupture and immune responses. Innate pro-inflammatory cytokines (e.g., IL-1ß, and TNF-α); mediators of activated T helper (Th)1 and Th17 cells (e.g., IFN-γ, and IL-17); and effector mechanisms of neutrophilic granulocytes, macrophages, and plasma cells are involved. On the other hand, HS lesions contain anti-inflammatory mediators (e.g., IL-10) and show limited activity of Th22 cells. The inflammatory vicious circle finally results in pain, purulence, tissue destruction, and scarring. HS pathogenesis is still enigmatic, and a valid animal model for HS is currently not available. All these aspects represent a challenge for the development of therapeutic approaches, which are urgently needed for this debilitating disease. Available treatments are limited, mostly off-label, and surgical interventions are often required to achieve remission. In this paper, we provide an overview of the current knowledge surrounding HS, including the diagnosis, pathogenesis, treatments, and existing translational studies.


Assuntos
Hidradenite Supurativa , Anti-Inflamatórios/uso terapêutico , Biomarcadores/metabolismo , Terapia Combinada , Citocinas/metabolismo , Hidradenite Supurativa/diagnóstico , Hidradenite Supurativa/etiologia , Hidradenite Supurativa/patologia , Hidradenite Supurativa/terapia , Humanos , Inflamação , Pele/patologia
4.
Cells ; 10(7)2021 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-34206914

RESUMO

Whilst the importance of keratinocytes as a first-line defense has been widely investigated, little is known about their interactions with non-resident immune cells. In this study, the impact of human keratinocytes on T cell effector functions was analyzed in an antigen-specific in vitro model of allergic contact dermatitis (ACD) to nickel sulfate. Keratinocytes partially inhibited T cell proliferation and cytokine production. This effect was dependent on the keratinocyte/T cell ratio and was partially reversible by increasing the number of autologous dendritic cells. The inhibition of T cell proliferation by keratinocytes was independent of the T cell subtype and antigen presentation by different professional antigen-presenting cells. Autologous and heterologous keratinocytes showed comparable effects, while the fixation of keratinocytes with paraformaldehyde abrogated the immunosuppressive effect. The separation of keratinocytes and T cells by a transwell chamber, as well as a cell-free keratinocyte supernatant, inhibited T cell effector functions to the same amount as directly co-cultured keratinocytes, thus proving that soluble factor/s account for the observed suppressive effects. In conclusion, keratinocytes critically control the threshold of inflammatory processes in the skin by inhibiting T cell proliferation and cytokine production.


Assuntos
Inflamação/imunologia , Inflamação/patologia , Queratinócitos/patologia , Linfócitos T/imunologia , Apresentação do Antígeno/imunologia , Biomarcadores/metabolismo , Comunicação Celular , Proliferação de Células , Forma Celular , Microambiente Celular , Dermatite de Contato/imunologia , Dermatite de Contato/patologia , Humanos , Hipersensibilidade/imunologia , Hipersensibilidade/patologia , Queratinócitos/ultraestrutura , Modelos Biológicos , Pele/imunologia , Pele/patologia , Solubilidade , Linfócitos T/ultraestrutura
5.
Artigo em Inglês | MEDLINE | ID: mdl-33803324

RESUMO

Incidence of sexually transmitted infections (STIs) such as chlamydia, gonorrhea, and syphilis has increased in recent years in the US and in European countries. In order to implement effective educational programs, the interests of target populations have to be identified. Since the internet is an important source of information-gathering on health issues, this study investigates web search data in large German cities related to STIs. Google Ads Keyword Planner was used to identify STI-related terms and their search volume in eleven German cities from June 2015 to May 2019. The data obtained were analyzed descriptively with regard to total search volumes, search volumes of specific thematic areas, and search volumes per 100,000 inhabitants. Overall, 741 terms with a total search volume of 5,142,560 queries were identified, with more than 70% of all search queries including a specific disease and "chlamydia" being the overall most often searched term (n = 1,196,160). Time courses of search behavior displayed a continuous interest in STIs with synchronal and national rather than regional peaks. Volumes of search queries lacked periodic patterns. Based on the findings of this study, a more open public discussion about STIs with linkage to increased media coverage and clarification of responsibilities among all STI-treating disciplines concerning management of STIs seem advisable.


Assuntos
Infecções por Chlamydia , Gonorreia , Infecções por HIV , Doenças Sexualmente Transmissíveis , Infecções por Chlamydia/epidemiologia , Cidades , Europa (Continente) , Humanos , Internet , Doenças Sexualmente Transmissíveis/epidemiologia
6.
J Affect Disord ; 282: 939-944, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33601738

RESUMO

BACKGROUND: The aim of this study was to investigate the association between skin disorders and depression in children and adolescents in Germany. METHODS: This retrospective case-control study was based on data from the Disease Analyzer database (IQVIA). The present study included children and adolescents diagnosed for the first time with depression in 185 pediatric practices between January 2017 and December 2019 (index date) and matched controls without depression. Chronic skin conditions documented within 12 months prior to the index date (i.e. date of first depression diagnosis) were included in the analyses if their prevalence was at least 0.5% in the study population. Associations between nine different skin disorders and depression (dependent variable) were analyzed in a conditional logistic regression model. RESULTS: This study included 7,061 cases with depression and 7,061 matched controls without depression (mean age 11.3 (SD: 3.8) years; 53.4% female). Three disorders were significantly associated with depression: atopic dermatitis/eczema (OR = 1.50, 95% CI = 1.37-1.64), nail disorders (OR = 1.84, 95% CI = 1.20-2.82), and hair loss (OR = 1.84, 95% CI = 1.30-2.60). In sex-stratified regression analyses, atopic dermatitis/eczema (OR = 1.43, 95% CI = 1.26-1.61) and hair loss (OR = 2.04, 95% CI = 1.37-3.03), were significantly associated with depression in females, since only atopic dermatitis/eczema was associated with depression (OR = 1.58, 95% CI = 1.39-1.80) in males. However, strong non-significant association was additionally observed for nail disorders (OR = 2.07, 95% CI = 1.07-4.01), and pigmentation disorders (OR = 1.93, 95% CI = 1.05-3.54) in females. CONCLUSIONS: Some skin disorders are positively associated with depression in children and adolescents. Further research is needed for better understanding of the underlying mechanisms and mediating factors.


Assuntos
Depressão , Dermatite Atópica , Adolescente , Estudos de Casos e Controles , Criança , Depressão/epidemiologia , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Estudos Retrospectivos
11.
Diagn Microbiol Infect Dis ; 88(3): 225-232, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28456430

RESUMO

Due to increased migration, Chagas disease has become an international health problem. Reliable diagnosis of chronically infected people is crucial for prevention of non-vectorial transmission as well as treatment. This study compared four distinct PCR methods for detection of Trypanosoma cruzi DNA for the use in well-equipped routine diagnostic laboratories. DNA was extracted of T. cruzi-positive and negative patients' blood samples and cultured T. cruzi, T. rangeli as well as Leishmania spp. One conventional and two real-time PCR methods targeting a repetitive Sat-DNA sequence as well as one conventional PCR method targeting the variable region of the kDNA minicircle were compared for sensitivity, intra- and interassay precision, limit of detection, specificity and cross-reactivity. Considering the performance, costs and ease of use, an algorithm for PCR-diagnosis of patients with a positive serology for T. cruzi antibodies was developed.


Assuntos
Doença de Chagas/diagnóstico , Técnicas de Diagnóstico Molecular/métodos , Reação em Cadeia da Polimerase/métodos , Trypanosoma cruzi/isolamento & purificação , Adolescente , Adulto , Sangue/parasitologia , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Trypanosoma cruzi/genética , Adulto Jovem
12.
BMJ Open ; 7(1): e013960, 2017 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-28093440

RESUMO

PURPOSE: Chagas disease (CD) has become a global health issue mainly due to migration. Germany lacks surveillance data and is home to a large Latin American immigrant population. Recognising that Bolivia is the country with the highest CD prevalence in Latin America, this cross-sectional, descriptive pilot study investigated CD and associated factors among citizens of Bolivian origin living in Munich, Germany. METHODS: Participants completed a questionnaire in order to collect socioeconomic and health-related data. In addition, serology was performed. In case of positive serological tests, PCR diagnostic and clinical staging together with disease management was initiated. Qualitative research was conducted to identify personal and community barriers as well as strategies to increase CD awareness among the population at risk. RESULTS: Between June 2013 and June 2014, 43 people from Bolivia (or descendants) were enrolled. A total of 9.3% (4/43), of whom two women were of childbearing age, tested seropositive (ELISA and IFAT), and one also by PCR. For 2/4 positive participants, clinical evaluation was performed and the indeterminate form of CD was diagnosed. Knowledge about CD symptoms and ways of transmission were completely absent among 55.8% (24/43, 2/4 with CD) and 30.2% (13/43, 1/4 with CD) of participants, respectively. A total of 27.9% (12/43, 0/4 with CD) of participants had donated blood prior to the study, whereas 62.8% (27/43, 3/4 with CD) were motivated to donate blood in the future. The qualitative research identified lack of knowledge as well as stigma and fears related to CD. CONCLUSIONS: Despite the small number of participants, the prevalence of CD as well as the potential risk of non-vectorial transmission was alarming. Campaigns adapted for Latin American migrants as well as control strategies should be developed and put in place in order to prevent non-vectorial transmission and actively detect cases of CD in Germany.


Assuntos
Doença de Chagas/epidemiologia , Emigrantes e Imigrantes/estatística & dados numéricos , Adolescente , Adulto , Idoso , Bolívia/etnologia , Doença de Chagas/sangue , Doença de Chagas/diagnóstico , Criança , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Reação em Cadeia da Polimerase , Prevalência , Fatores Socioeconômicos , Adulto Jovem
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