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Hur personer med psoriasis upplever livet med sjukdomen. En litteraturstudieNordwall, Helen January 2009 (has links)
Psoriasis är en kronisk inflammatorisk hudsjukdom som drabbar cirka tre procent av befolkningen i Sverige. Den är inte smittsam. Både män och kvinnor i alla åldrar drabbas. Orsaken till hudsjukdomen psoriasis är okänd. Det kan bero på en ärftlig komponent. Cirka 30 procent av personer med diagnosen psoriasis drabbas av ledbesvär. Sjukdomen debuterar vanligtvis i 10-35 års ålder. Hudförändringarna ser vanligtvis ut som lätt upphöjd hudyta som har en skarp gräns, den kan ha olika nyanser av rodnad, ha en stearinliknande fjällning och förekommer symmetriskt på kroppen. Eftersom huden är kroppens största organ syns det tydligt för andras ögon när hudens tillstånd är som värst och det kan upplevas motbjudande. Syftet med denna litteraturstudie var att belysa hur personer med psoriasis upplever livet med sjukdomen. I resultatet användes sex vetenskapliga artiklar som analyserades och kategoriserades utifrån Friberg (2006). Det framkom att den drabbades livsvärld påverkades negativt. Psoriasis påverkar den drabbade individen inte bara fysiskt utan även psykiskt och socialt. Den drabbade personen blir också medveten om hur hans/hennes hudkostym ser ut och undviker medvetet att komma i närheten av folksamlingar för att slippa folks kommentarer och negativa reaktioner samt människornas nyfikna blickar. Vardagslivet omkullkastas, aktiviteterna blir inskränkta, det sociala livet och relationerna till medmänniskor begränsas på grund av sjukdomen. / Program: Sjuksköterskeutbildning
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Att leva med psoriasis : En litteraturstudieIsufi, Jetish, Lövqvist, Jessica January 2013 (has links)
Psoriasis är en inflammatorisk hudsjukdom som uppkommer i perioder. Sjukdomens behandling går ut på att lindra patientens besvär men går inte helt att bota. Dagens samhälle kan uppfattas som ytligt och utseendefixerat vilket leder till att personer som lider av psoriasis kan känna sig annorlunda på grund av den förändrade huden. Syftet med uppsatsen är att belysa patienters erfarenheter av att leva med psoriasis. Metoden som används är en litteraturstudie utifrån Axelsson (2008). Åtta kvalitativa artiklar har använts för att skildra patienters upplevelse av sjukdomen. Resultatet visar att upplevelsen av den egna kroppen är negativ då huden förändras och gör att den ser annorlunda ut. Negativa upplevelser och skam om den egna kroppen kan leda till isolering. Personer som lider av sjukdomen ser negativt på att ge sig in i nya sociala och intima relationer av rädsla för att bli avvisade på grund av sin hud. Att våga och kunna acceptera sjukdomen är svårare för unga personer än äldre som levt med sjukdomen i flera år. Att vårdas på en vårdavdelning upplever patienterna som en ”fristad”. Kontakten med andra patienter är viktig, ofta uppkommer samtal om problem som uppstår under sjukdomens gång samt tröst från patienter som förstår varandra. Vårdpersonalens kunskap om patienternas psykosociala ohälsa vid psoriasis är låg. Att öka kunskapen hos vårdpersonalen kommer att leda till en ökad förståelse om patienternas problem i samhället. Diskussionen mellan vårdpersonal och patienter kan leda till att lidandet minskar och patienten kan acceptera sjukdomen. / Program: Sjuksköterskeutbildning
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Nanodispersões de fase líquido-cristalina como carreadoras de siRNA no tratamento tópico da psoríase: Avaliação em modelos in vitro e in vivo / Liquid crystalline nanodispersions as a siRNA carrier in the topical treatment of psoriasis: Evaluation in in vitro and in vivo modelsDepieri, Lívia Vieira 05 August 2016 (has links)
A terapia gênica por interferência de RNA (RNAi) é um processo de silenciamento gênico pós-transcricional onde moléculas de small interfering RNA (siRNA) específicas são capazes de suprimir a expressão de um determinado gene. Atualmente, é uma abordagem terapêutica promissora para o tratamento de muitas doenças graves, incluindo doenças cutâneas. No entanto, dificuldades relacionadas à administração e à biodistribuição limitam a utilização clínica dos siRNAs. Neste contexto, foi proposto o uso de um nanocarreador a base de cristais líquidos para viabilizar a aplicação de siRNAs no tratamento tópico da psoríase. A nanodispersão líquido-cristalina (NLC) desenvolvida, composta por monoleína, ácido oleico, polietilenoimina e fase aquosa (8:2:1:89, p/p/p/p), foi capaz de superar as barreiras da via de administração tópica, bem como as limitações resultantes das características das moléculas de siRNA. A NLC foi capaz de complexar o siRNA, protege-lo por 24 h da degradação enzimática e liberá-lo de forma intacta. A NLC promoveu uma alta taxa de captação celular do siRNA em fibroblastos e macrófagos. Sua aplicação tópica pode ser considerada segura para a pele, pois manteve a viabilidade da epiderme humana reconstruída acima de 50% e a quantidade de IL-1? liberada foi inferior a 60 pg/mL. A NLC apresentou eficácia em promover a liberação funcional do siRNA nos modelos in vitro avaliados. No modelo de pele humana reconstruída psoriática, reduziu os níveis de IL-6 (~ 70%) após um único tratamento por 6 h e, os níveis do RNAm IL6 (~ 50%) após o tratamento por 3 dias consecutivos. Em macrófagos, reduziu os níveis do RNAm Tnf em 40% após o tratamento concomitante com LPS por 24 h e, em 60% após o tratamento por 24 h pós-estímulo prévio com LPS. A eficácia foi ainda maior com o pré-tratamento por 24 h seguido do estímulo com LPS, que normalizou os níveis do RNAm Tnf. O tratamento tópico com a NLC veiculando siRNA Tnf foi eficaz em reduzir significativamente os níveis do RNAm Tnf nos modelos in vivo de inflamação cutânea aguda induzida por TPA (~ 60%) e de psoríase induzida por imiquimode (~ 90%) avaliados. No modelo in vivo de psoríase, o tratamento tópico com a NLC veiculando siRNA Tnf também reduziu significativamente a atividade da mieloperoxidade (~ 65%) e a espessura da epiderme (~ 70%) em comparação aos grupos controle. Também foi eficaz na melhora fenotípica dos animais, reduzindo o rubor, descamação, acantose e o número de ataques de coceira, resultados da redução do processo inflamatório decorrente da ação efetiva das moléculas de siRNA Tnf. A NLC também promoveu a penetração cutânea das moléculas de siRNA nas camadas mais profundas da pele, in vivo. Face aos resultados obtidos, pode-se concluir que a NLC é uma estratégia relevante para a administração tópica de siRNAs, que mostrou potencial terapêutico para suprimir genes específicos relacionados a doenças de pele. / Gene therapy by RNA interference (RNAi) is a post-transcriptional gene silencing process in which specific small interfering RNA (siRNA) molecules can suppress the expression of a particular gene. Currently, is a promising therapeutic approach for the treatment of many severe disorders, including skin diseases. However, difficulties related to the administration and biodistribution limit the clinical use of siRNAs. In this context, a nanocarrier based in liquid crystal has been proposed to enable the application of siRNAs in the topical treatment of psoriasis. The liquid crystalline nanodispersion (LCN) developed, composed by monoolein, oleic acid, polyethylenimine and aqueous phase (8:2:1:89, w/w/w/w), was able to overcome the barriers of topical administration route, as well as limitations resulting from the characteristics of the siRNA molecules. The LCN was able to complex the siRNA, protect it for 24 h from enzymatic degradation and release it in an intact form. The LNC promoted a high cellular uptake of siRNA in fibroblasts and macrophages. Its topical application can be considered safe to the skin since viability of the reconstructed human epidermis remained above 50% and the amount of IL-1? released is less than 60 pg/mL. The LCN showed efficacy in promoting functional release of siRNA in in vitro models evaluated. In psoriatic reconstructed human skin model, it reduced the IL-6 levels (~ 70%) after a single treatment for 6 h and the mRNA IL6 levels (~ 50%) after treatment for 3 consecutive days. In macrophages, it reduced the mRNA Tnf levels in 40% after the concomitant treatment with LPS for 24 h and, in 60% with treatment for 24 h after prior stimulation with LPS. The efficiency was higher with the pretreatment for 24 h followed by stimulation with LPS, that normalized the RNAm Tnf levels. Topical treatment with NLC carrying siRNA Tnf was effective in reduce significantly the mRNA Tnf levels in in vivo models of skin acute inflammation induced by TPA (~ 60%) and of psoriasis induced by imiquimod (~ 90%) evaluated. In the in vivo model of psoriasis, topical treatment with the NLC carrying siRNA Tnf also significantly reduced activity of myeloperoxidase (~ 65%) and the epidermis thickness (~ 70%) compared to control groups. It has also been effective in animal phenotypic improvement, reducing redness, desquamation, acanthosis and the number of itch attacks, results of the reduction in inflammatory process obtained by the effective action of siRNA Tnf molecules. The LCN also promoted the penetration of siRNA molecules into the deeper layers of the skin in vivo. With the results obtained, we can conclude that the LCN is a relevant strategy for topical administration of siRNAs, which showed therapeutic potential to suppress specific genes related to skin diseases.
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針灸治療牛皮癬的取穴研究區智堅, 01 January 2009 (has links)
No description available.
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Efeitos do óleo da semente do maracujá na psoríase experimental / Effects of passion fruit seed oil on experimental psoriasisAna Carolina Miguel Alvarenga 11 June 2018 (has links)
A psoríase é uma doença de pele inflamatória crônica, que afeta cerca de 2-4% da população mundial. Se desenvolve ao longo do tempo, principalmente no final da adolescência ou início da idade adulta e depende de uma complexa interação entre fatores genéticos e ambientais. Dados experimentais demostram que a dermatite induzida por imiquimode (IMQ) em camundongos assemelha-se estreitamente às lesões de psoríase humana, tanto nas características fenotípicas e histológicas como no desenvolvimento das lesões na epiderme. O estudo avaliou os efeitos anti-inflamatórios do óleo de semente de maracujá (Passiflora edulis) no tratamento da psoríase, utilizando a análise histológica e imunológica da epiderme. O experimento foi realizado com 36 camundongos Balb/c, os quais foram submetidos à indução da psoríase por imiquimode, por 10 dias consecutivos. O tratamento foi realizado com óleo de semente de maracujá in natura 100%, pomada LECIGEL® 2%, pomada associação de óleo de semente de maracujá 20% e LECIGEL® 2%, por 15 dias. Tanto o óleo da semente do maracujá quanto a associação do mesmo ao LECIGEL® diminuíram o quadro inflamatório induzido por imiquimode nas orelhas tratadas. Através das análises imuno-histoquímicas realizadas na epiderme (PCNA, IL-6, VEGF, CD34), observou-se um aumento na formação de corpos apoptóticos, diminuição a hiperplasia epitelial e redução do infiltrado inflamatório. Os resultados deste experimento demonstraram que o óleo da semente do maracujá desempenha um efeito anti-inflamatório no tratamento da psoríase induzida por imiquimode. / Psoriasis is a chronic inflammatory skin disease that affects about 2-4% of the world\'s population. It develops over time, especially in late adolescence or early adulthood and depends on a complex interaction between genetic and environmental factors. Experimental data show that imiquimode-induced dermatitis (IMQ) in mice closely resembles human psoriasis lesions, both in phenotypic and histological characteristics and in the development of lesions in the epidermis. The study evaluated the anti-inflammatory effects of passion fruit (Passiflora edulis) oil in the treatment of psoriasis, using the histological and immunological analysis of the epidermis. The experiment was performed with 36 Balb / c mice, which were submitted to psoriasis induction by imiquimode, for 10 consecutive days. The treatment was carried out with 100% fresh passion fruit seed oil, LECIGEL ® 2% ointment, 20% passion fruit seed oil ointment and LECIGEL ® 2% for 15 days. Both passionflower seed oil and its association with LECIGEL ® decreased the imiquimod-induced inflammation in the treated ears. Through the immunohistochemical analyzes performed on the epidermis (PCNA, IL-6, VEGF, CD34), an increase in the formation of apoptotic bodies, decrease in epithelial hyperplasia and reduction of inflammatory infiltrate was observed. The results of this experiment suggest that passion fruit seed oil has an anti-inflammatory effect in the treatment of imiquimode-induced psoriasis.
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Avaliação do teste T-SPOT.TB no diagnóstico de infecção tuberculosa latente em pacientes com psoríase / Assessment of T-SPOT-TB test for the diagnosis of latent tuberculosis infection in patients with psoriasisEmerson Vasconcelos de Andrade Lima 20 April 2010 (has links)
Introdução: A terapêutica da psoríase foi modificada pela introdução dos imunobiológicos, que permitem melhor controle da doença e melhor qualidade de vida aos pacientes, mas promovem aumento do risco de tuberculose latente, exigindo diagnóstico antecedendo seu início. Objetivo: Avaliar o desempenho do teste T-SPOT.TB no diagnóstico de infecção tuberculosa latente em pacientes com psoríase. Métodos: Em estudo experimental, prospectivo, analítico, com comparação de grupos,de prevenção primária, para validade de teste diagnóstico, 33 pacientes com psoríase (grupo psoríase) e 30 pacientes com outras doenças dermatológicas (grupo base), atendidos nos Ambulatório de Dermatologia Geral ou de Psoríase do Centro de Estudos Dermatológicos do Recife, da Santa Casa de Misericórdia, entre fevereiro e novembro de 2009, foram submetidos aos testes do PPD e T-SPOT.TB. Para ambos os grupos, admitiu-se inclusão com idade mínima de 18 anos e critérios de exclusão doenças ou condições fisiológicas que comprometessem a competência imunológica, exceto psoríase, para o grupo psoríase. Adotou-se a técnica de Mantoux para o teste do PPD e uma variante simplificada da técnica Enzyme-Linked Immunospot para a determinação de células T efetoras, secretoras de IFN-g em resposta à estimulação pelos antígenos específicos do M. tuberculosis para o teste T-SPOT.TB. As variáveis dependentes foram os resultados do teste T-SPOT.TB contra antígenos ESAT-6, CFP-10, e os resultados do teste do PPD, considerando enduração de 0-4 mm: não reator; 5-9 mm: reator fraco; ≥ 10 mm: reator forte. As variáveis independentes foram: idade, sexo, cor da pele, tempo de evolução da psoríase, ocupação, história de contato intradomiciliar e renda, alcoolismo e gravidade da doença. Foram submetidos a teste Qui quadrado ou exato de Fisher, em nível de significância de 0, 05, assim como ao teste de Mantel-Haenszel, três modelos comparando o teste T-SPOT.TB com teste do PPD, contato intradomiciliar e associação teste do PPD e contato intradomiciliar. A pesquisa foi aprovada pelos Comitês de Ética da Universidade Federal de Pernambuco e Universidade de São Paulo. Resultados: O grupo psoríase diferiu do grupo base quanto a razão de sexo com predomino do masculino (razão=0,7:1; p=0,047); maior idade média 42,1±1,9 anos (contra 34,1±1,4 anos no grupo base, p=0,023); fototipos I e II (p=0,020); menor nível de instrução e renda média mensal e contato intradomiciliar com tuberculose menos freqüente (p=0,001). Os grupos também diferiram quanto à positividade do teste do PPD (maior no grupo base; p=0,001). O teste T-SPOT.TB apresentou sensibilidade e especificidade de 9,1% e 95,5%, no modelo 1, 27,3% e 60%, no modelo 2, e valores de 60% e 53,3%, respectivamente no modelo 3. Foi no modelo 1 do grupo psoríase que o teste TSPOT. TB mostrou a maior concordância e o maior valor de Odds Ratio ponderado pelo teste de Mantel-Haenszel, tendo esses dois parâmetros significância estatística, quando comparados aos outros dois modelos. Conclusões: O teste T-SPOT.TB apresentou maior capacidade de diagnosticar casos negativos para tuberculose latente, constituindo-se numa opção para triagem de pacientes na instituição de terapêutica com imunobiológicos. / Introduction: The therapy for psoriasis was modified by the introduction of immunebiological products that allow better disease control and better quality of life for patients, but promotes increased risk forf latent tuberculosis, requiring diagnosis shortly before its establishment. Purpose: To assess the performance of T-SPOT.TB test for the diagnosis of latent tuberculosis infection in patients with psoriasis. Methods: Within a experimental, prospective, analytic, clinical assay type study, with comparison of groups, to validate a diagnostic test, 33 patients with psoriasis (psoriasis group) and 30 patients with other dermatological diseases (basis group), attempted at General Dermatology and Psoriasis Out-patients Departments of Recife\'s Dermatological Studies Center of Santa Casa de Misericórdia, from February to November 2009, were submitted to PPD and TSPOT. TB tests. For both groups, we admitted 18 years as minimal age for inclusion. The exclusion criteria included disease ou physiological conditions that compromised immunological competence, except psoriasis to psoriasis group. We used Mantoux technique for PPD test and a simplified variant of Enzyme-Linked Immunospot technique to determine effector T cells, secretors of IFN-g in response to M. tuberculosis specific antigens, to T-SPOT.TB test. Dependent variables were the results of T-SPOT.TB test against ESAT-6 and CPF-10 antigens, and the results to PPD test, considering enduration of 0-4 mm as non reactor; 5-10 mm weak reactor and ≥ 10 mm, strong reactor. Independent variables were age, sex, skin color, psoriasis evolution time, occupation, history of intradomiciliar contact and income, alcoolism and disease grade. Three models, comparing T-SPOT.TB test to PPD test, intradomiciliar contact and both, were submitted to Qui Squared test or Exact Fisher Test, at significance level of 0.05, as well as to Mantel- Haenszel test. The research has been approved by Ethics Committee of Universidade Federal de Pernambuco e Universidade de São Paulo. Results: Psoriasis group differed from base group on sex ratio with predominance of male gender (rate=0.7:1; p=0,047), major mean age (42,1 ± 1.9 years against 34,1 ± 1.4 years in basic group, p = 0,023) phototypes I and II (p = 0,020); lower scholarship, income and less frequent intradomiciliar contact with tuberculosis (p = 0,001). The groups also differed on the positivity of PPD test (greater in base group; p = 0,001). T-SPOT.TB test had sensibility and specificity of 9,1% and 95.5%, in model 1; 27,3% and 60%, in model 2, and values of 60% and 53,3% respectively in model 3. Model 1 showed greater concordance and highest value of Odds Ratio test weighted by Mantel-Haenszel test, having these two parameters statistical significance when compared to the other two models. Conclusions: T-SPOT.TB test had great ability to diagnose negative cases for latent tuberculosis, and constitutes an option for screening patients to immunobiological therapy administration.
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Studies on Vitamin A Signaling in Psoriasis : A Comparison Between Normal and Lesional KeratinocytesKarlsson, Teresa January 2002 (has links)
<p>Vitamin A and metabolites (retinoids) are crucial for normal epidermal maturation. Physiological effects are mediated by retinoic acid (RA) that activates nuclear retinoic acid receptors (RARs) in complexes with retinoid X receptors (RXRs), resulting in altered gene transcription.</p><p>Psoriasis is a common disease with unknown etiology. Lesions display inflammation, hyperproliferation, and disturbed epidermal maturation. Treatments include topical or oral synthetic retinoids that allegedly bind to and activate the RARs.</p><p>The mRNA expression of retinoid receptors RARα/γ and RXRα was studied in normal and psoriatic skin samples. RARα and RXRα were significantly reduced in psoriatic plaques as compared to non-lesional and normal skin. <i>In situ</i> immunofluorescence detection revealed altered distribution patterns of the receptor proteins in lesional skin. All three receptor proteins were more intensely detected in the lower half of the epidermis but were significantly reduced in the superficial epidermis compared to both normal and non-lesional skin. </p><p>In order to evaluate the retinoid signaling system in psoriatic lesions, we compared the effect of topical RA on the expression of the cellular RA-binding protein II (CRABPII) in psoriatic and normal skin. CRABPII was induced by RA on mRNA and protein level in non-lesional and normal skin but not in lesional skin, where the basal expression of CRABPII was already up-regulated.</p><p>Changes in retinoid signaling during keratinocyte differentiation <i>in vitro </i>were studied by measuring retinoid receptor and RAR-ligand levels<i>.</i> Exposure to differentiation-inducing levels of calcium, phorbol myristate acetate (PMA) or interferon-γ (IFNγ) led to increased RAR-ligand levels but PMA and IFNγ caused receptor protein loss due to increased proteasomal degradation. Since an increased IFNγ level is a hallmark of psoriatic inflammation, this might be a cause of altered retinoid signaling in lesional epidermis.</p><p><i>Conclusion:</i> Keratinocyte differentiation is accompanied by alterations in the retinoid signaling system. In psoriatic lesions, this system appears to be dysfunctioning due to reduced retinoid receptor levels, which might be an important event in the pathogenesis of the disease.</p>
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Studies on Vitamin A Signaling in Psoriasis : A Comparison Between Normal and Lesional KeratinocytesKarlsson, Teresa January 2002 (has links)
Vitamin A and metabolites (retinoids) are crucial for normal epidermal maturation. Physiological effects are mediated by retinoic acid (RA) that activates nuclear retinoic acid receptors (RARs) in complexes with retinoid X receptors (RXRs), resulting in altered gene transcription. Psoriasis is a common disease with unknown etiology. Lesions display inflammation, hyperproliferation, and disturbed epidermal maturation. Treatments include topical or oral synthetic retinoids that allegedly bind to and activate the RARs. The mRNA expression of retinoid receptors RARα/γ and RXRα was studied in normal and psoriatic skin samples. RARα and RXRα were significantly reduced in psoriatic plaques as compared to non-lesional and normal skin. In situ immunofluorescence detection revealed altered distribution patterns of the receptor proteins in lesional skin. All three receptor proteins were more intensely detected in the lower half of the epidermis but were significantly reduced in the superficial epidermis compared to both normal and non-lesional skin. In order to evaluate the retinoid signaling system in psoriatic lesions, we compared the effect of topical RA on the expression of the cellular RA-binding protein II (CRABPII) in psoriatic and normal skin. CRABPII was induced by RA on mRNA and protein level in non-lesional and normal skin but not in lesional skin, where the basal expression of CRABPII was already up-regulated. Changes in retinoid signaling during keratinocyte differentiation in vitro were studied by measuring retinoid receptor and RAR-ligand levels. Exposure to differentiation-inducing levels of calcium, phorbol myristate acetate (PMA) or interferon-γ (IFNγ) led to increased RAR-ligand levels but PMA and IFNγ caused receptor protein loss due to increased proteasomal degradation. Since an increased IFNγ level is a hallmark of psoriatic inflammation, this might be a cause of altered retinoid signaling in lesional epidermis. Conclusion: Keratinocyte differentiation is accompanied by alterations in the retinoid signaling system. In psoriatic lesions, this system appears to be dysfunctioning due to reduced retinoid receptor levels, which might be an important event in the pathogenesis of the disease.
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Polimorfismos del receptor Fc gamma en patología cutánea inmunomediada: Papel en la patogenia del penfigoide ampolloso y en la respuesta a tratamiento biológico en la psoriasisGuilabert Vidal, Antonio 16 February 2012 (has links)
Los receptores Fc-gamma (Fc-gR) median muchas de las funciones inmunes de la IgG. Están presentes en numerosas células del sistema inmune y su activación (tras la unión al fragmento Fc de la IgG) permite el desarrollo de funciones tales como la fagocitosis, la citotoxicidad dependiente de anticuerpos y la liberación de enzimas proteolíticas. Existen polimorfismos genéticos que modifican la afinidad de los Fc-gR y por tanto su capacidad funcional. Estos polimorfismos se han relacionado con enfermedades autoinmunes, infecciosas y con la eficacia de agentes monoclonales. El penfigoide ampolloso (PA) es una patología ampollosa autoinmune caracterizada por el deposito de autoanticuerpos en la membrana basal de la piel. Estos anticuerpos activan a neutrófilos vía el receptor Fc-gR, los cuales liberan enzimas proteolíticas que degradan la membrana basal causando el daño tisular. Los agentes monoclonales han revolucionado el tratamiento de las formas moderadas y graves de psoriasis. Sin embargo, en torno a un 30% de los pacientes no presentarán una respuesta adecuada. En la actualidad no existen factores farmacogenéticos definidos que puedan predecir la respuesta a biológicos en la psoriasis.
Teniendo en cuenta el contrastado papel del los Fc-gR en modelos animales de PA, los polimorfismos genéticos de Fc-gR podrían relacionarse a nivel clínico con el PA, tanto como marcadores como modificadores de esta enfermedad. Por otra parte, los polimorfismos de Fc-gR también podrían predecir la respuesta a biológicos en la psoriasis, ya que los agentes empleados (etanercept, infliximab y adalimumab) contienen el fragmento Fc en su estructura. Esta influencia podría venir dada por un aumento en las capacidades citotóxicas de estos agentes, o por una alteración de los mecanismos de eliminación de estos fármacos dependientes del sistema reticuloendotelial.
El objetivo de esta tesis fue estudiar la influencia de los polimorfismos de Fc-gR en 2 patologías cutáneas inmunomediadas mediante el estudio genético de grupos de pacientes y controles. Por un lado, se pretendía detectar si los polimorfismos de Fc-gR se asocian al PA o si modifican el pronostico de esta enfermedad, y por otro, si dichos polimorfismos son marcadores farmacogenéticos de respuesta clínica en aquellos pacientes psoriásicos tratados con agentes biológicos.
Se realizó estudio genético de los polimorfismos Fc-gRIIA-H131R, Fc-gRIIB-I187T y Fc-gRIIIA-V158F en un grupo de 41 pacientes con PA y un grupo control de 115 individuos sanos y de Fc-gRIIA-H131R y Fc-gRIIIA-V158F en un grupo de 70 pacientes con psoriasis tratados agentes anti-TNF-alfa. Se realizó un análisis retrospectivo de los datos clínicos de los pacientes con PA y una valoración clínica retrospectiva de la respuesta a biológicos en pacientes con psoriasis.
En el caso del PA observamos, en un modelo multivariante, una tendencia a la asociación del alelo F de Fc-gRIIIA-V158F con las formas más graves de PA, definidas como la necesidad de añadir tratamiento inmunosupresor. Por otra parte, los pacientes psoriáticos con alelos de alta afinidad (aislados o en combinación) de los polimorfismos a estudio presentaron, de forma independiente, una respuesta terapéutica más rápida a terapia biológica en forma de un porcentaje de superficie corporal afecta menor a las 6-8 semanas de tratamiento, probablemente en relación con una mayor eliminación de células patogénicas con TNF-alfa en membrana.
Nuestros resultados tienen implicación clínica ya que, por un lado, los pacientes con PA y presencia del alelo F, podría beneficiarse de la introducción temprana de inmunosupresores y, por otro, la presencia de alelos de alta afinidad en los polimorfismos de Fc-gR podría predecir una respuesta clínica mas precoz en pacientes con psoriasis tratados con biológicos, lo cual puede ser de especial importancia en casos graves. / Fc gamma receptors (Fc-gammaR) mediate most of the immune functions of IgG. There are single-nucleotide polimorphims affecting Fc-gammaR genes that influence affinity and thus functions of Fc-gammaR. These polymorphisms have been linked clinically with infectious and autoimmune disease but also with the degree of response to monoclonal antibodies containing the Fc fragment. Bullous pemphigoid (BP) is an autoimmune disease where pathogenic antibodies bind antigens in the basal membrane of the skin. Such antibodies activate neutrophils through Fc-gammaR, which make these cells liberate proteolytic enzymes that cause tissue injury and blisters in the skin. Monoclonal agents have improved greatly the outcome of patients with psoriasis. However up to 30% does not achieve a significant response. There are not currently pharmacogenetic markers that could predict the outcome of biological therapy in psoriasis.
The main objective of this thesis was to study the influence of Fc-gammaR polymorphisms in 2 immune-mediated skin diseases: a) a possible influence, in terms of susceptibility or disease modification, of Fc-gammaR polymorphisms in BP; and b) the potential role of Fc-gammaR polymorphisms as pharmacogenetic markers in patients with psoriasis treated with anti-TNF-alpha therapy.
We performed the determination of the genotype of Fc-gammaRIIA-H131R, Fc-gammaRIIB-I187T and Fc-gammaRIIIA-V158F in 41 patients with BP and 115 controls and Fc-gammaRIIA-H131R and Fc-gammaRIIIA-V158F genotypes in 70 patients with psoriasis that underwent anti-TNF-alpha treatment. Clinical charts were reviewed in order to establish correlations.
In the BP study, we observed an association between the presence of Fc-gammaRIIIA-158F with the most severe forms of BP, defined as the need for immunosuppressants. With regard to the psoriasis study, we detected that patients with high affinity alleles (alone or in combination) presented a quick response to biologics, measured as a lower body surface area affected in the week 6-8.
Our results present clinical implications, since for example, patients with BP harboring the F allele may benefit from an early introduction of immunosuppressants. On the other hand, the presence of Fc-gammaR high affinity alleles may predict an early response to biologics in psoriasis, which may be critical especially in severe cases.
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Studies on vitamin A signaling in psoriasis : a comparison between normal and lesional keratinocytes /Karlsson, Teresa, January 2002 (has links)
Diss. (sammanfattning) Uppsala : Univ., 2002. / Härtill 4 uppsatser.
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