Detection of Type 1 Cytokines in Discoid Lupus Erythematosus

Toro, Jorge R.; Finlay, Deborah; Dou, Xiaogin; Zheng, Shi Chun; LeBoit, Philip E.; Connolly, M. Kari

doi:10.1001/archderm.136.12.1497

Cited by 45 publications

(62 citation statements)

References 19 publications

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“…Elevated levels of IFNγ messenger RNA have been described in DLE skin specimens relative to normal skin, and immunohistochemical analyses have shown a selective staining of IFNγ receptors in DLE skin samples compared to normal skin samples 4. IFNγ modulates the function of several populations of immune system cells, including B cells, T cells, and macrophages.…”

mentioning

confidence: 99%

Brief Report: Pharmacodynamics, Safety, and Clinical Efficacy of AMG 811, a Human Anti–Interferon‐γ Antibody, in Patients With Discoid Lupus Erythematosus

Werth

Fiorentino

Sullivan

et al. 2017

Arthritis & Rheumatology

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ObjectiveInterferon‐γ (IFNγ) is implicated in the pathogenesis of discoid lupus erythematosus (DLE). This study sought to evaluate a single dose of AMG 811, an anti‐IFNγ antibody, in patients with DLE.MethodsThe study was designed as a phase I randomized, double‐blind, placebo‐controlled crossover study of the pharmacodynamics, safety, and clinical efficacy of AMG 811 in patients with DLE. Patients received a single subcutaneous dose of AMG 811 (180 mg) or placebo. The patients in sequence 1 received AMG 811 followed by placebo, while those in sequence 2 received placebo followed by AMG 811. Pharmacodynamic end points included global transcriptional analyses of lesional and nonlesional skin, IFNγ blockade signature (IGBS) transcriptional scores in the skin and blood, keratinocyte IFNγ RNA scores, and serum levels of CXCL10 protein. Additional end points were efficacy outcome measures, including the Cutaneous Lupus Erythematosus Disease Area and Severity Index, and safety outcome measures.ResultsSixteen patients with DLE were enrolled in the study (9 in sequence 1 and 7 in sequence 2). AMG 811 treatment reduced the IGBS score (which was elevated in DLE patients at baseline) in both the blood and lesional skin. The keratinocyte IFNγ RNA score was not affected by administration of AMG 811. Serum CXCL10 protein levels (which were elevated in the blood of DLE patients) were reduced with AMG 811 treatment. The AMG 811 treatment was well tolerated but did not lead to statistically significant improvements in any of the efficacy outcome measures.ConclusionAMG 811 treatment led to changes in IFNγ‐associated biomarkers and was well tolerated, but no significant clinical benefit was observed in patients with DLE.

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mentioning

confidence: 99%

Brief Report: Pharmacodynamics, Safety, and Clinical Efficacy of AMG 811, a Human Anti–Interferon‐γ Antibody, in Patients With Discoid Lupus Erythematosus

Werth

Fiorentino

Sullivan

et al. 2017

Arthritis & Rheumatology

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“…antígenos, é uma forte promotora de citocinas Th1 (Toro et al, 2000;Vasconcelos, 2009). As citocinas Th2 são representadas principalmente pelas IL-4, IL-5, IL-6 e IL-10 (Toro et al, 2000;.…”

Section: Th1 O Interferon  (Ifn-) a Interleucina (Il) 2 (Il-2) E Ounclassified

“…As citocinas Th2 são representadas principalmente pelas IL-4, IL-5, IL-6 e IL-10 (Toro et al, 2000;.…”

Section: Th1 O Interferon  (Ifn-) a Interleucina (Il) 2 (Il-2) E Ounclassified

“…Alguns autores sugerem predomínio da resposta Th1 (Toro et al, 2000), enquanto outros defendem uma resposta Th2 (Stein et al, 1997).…”

Section: Th1 O Interferon  (Ifn-) a Interleucina (Il) 2 (Il-2) E Ounclassified

“…Os estudos sobre a participação das citocinas nas lesões cutâneas de LE são pouco frequentes (Stein et al, 1997;Toro et al, 2000;. Na literatura não foram encontrados relatos da participação de citocinas nas lesões orais de LE, o que nos motivou a realizar este trabalho.…”

Section: Th1 O Interferon  (Ifn-) a Interleucina (Il) 2 (Il-2) E Ounclassified

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Manifestações orais do lúpus eritematoso: padrão das citocinas do infiltrado inflamatório

Marques¹

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Dedicatória DedicatóriaAo meu marido, Telmo, pelo seu enorme amor e dedicação a mim, pelo incentivo e apoio incondicional a todos os meus sonhos e pela satisfação com conquistas minhas mais do que com as próprias.Aos meus filhos, Gustavo e Giulia, pelo carinho, incentivo e compreensão pelas frequêntes ausências.À minha mãe, Lourdes, por ter me ensinado a prezar a busca pelo conhecimento e por sua dedicação, estímulo e presença, com seu amor incondicional, em todos os momentos da minha vida.Ao meu pai, Jarbas, pelos bons momentos que convivemos.Ao meu irmão, Jarbas Eduardo, antes de tudo um amigo, grande incentivador do meu crescimento profissional.Aos meus cunhados, Thiers, Simone e Maria Alice, que tornam a minha família ainda melhor. Agradecimentos AgradecimentosAo meu orientador, Prof. Dr. Marcello Menta S. Nico, por sua condução firme, segura e participativa, com contribuições e ensinamentos valiosos em todos os momentos do desenvolvimento deste estudo, a quem aprendi a admirar e respeitar por sua sabedoria e dedicação. Agradeço pelo privilégio de ter trabalhado ao seu lado. À Profª. Dra. Sílvia Vanessa Lourenço, pela profissional dedicada, solícita, participativa, um exemplo a ser admirado e seguido. Devo, principalmente ao seu incentivo, apoio, ajuda e ensinamentos, a realização deste estudo. À Profª. Dra. Miriam Nacami Sotto, pela confiança, incentivo e ajuda para que este estudo pudesse ser realizado. À Dona Eli Maria, pela eficiência e competência na resolução de nossas dúvidas.

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Ultraviolet radiation–induced injury, chemokines, and leukocyte recruitment: An amplification cycle triggering cutaneous lupus erythematosus

Meller¹,

Winterberg²,

Gilliet³

et al. 2005

Arthritis & Rheumatism

214

200

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Objective. To investigate the activation and recruitment pathways of relevant leukocyte subsets during the initiation and amplification of cutaneous lupus erythematosus (LE).Methods. Quantitative real-time polymerase chain reaction was used to perform a comprehensive analysis of all known chemokines and their receptors in cutaneous LE lesions, and the cellular origin of these chemokines and receptors was determined using immunohistochemistry. Furthermore, cytokine-and ultraviolet (UV) light-mediated activation pathways of relevant chemokines were investigated in vitro and in vivo. Conclusion. Taken together, our data suggest an amplification cycle in which UV light-induced injury induces apoptosis, necrosis, and chemokine production. These mechanisms, in turn, mediate the recruitment and activation of autoimmune T cells and IFN␣-producing PDCs, which subsequently release more effector cytokines, thus amplifying chemokine production Dr.

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Detection of Type 1 Cytokines in Discoid Lupus Erythematosus

Cited by 45 publications

References 19 publications

Brief Report: Pharmacodynamics, Safety, and Clinical Efficacy of AMG 811, a Human Anti–Interferon‐γ Antibody, in Patients With Discoid Lupus Erythematosus

Brief Report: Pharmacodynamics, Safety, and Clinical Efficacy of AMG 811, a Human Anti–Interferon‐γ Antibody, in Patients With Discoid Lupus Erythematosus

Manifestações orais do lúpus eritematoso: padrão das citocinas do infiltrado inflamatório

Ultraviolet radiation–induced injury, chemokines, and leukocyte recruitment: An amplification cycle triggering cutaneous lupus erythematosus

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