Pathogenic mechanisms involving the interplay between adipose tissue and auto-antibodies in rheumatoid arthritis

Rosa, I. Arias de la; Escudero‐Contreras, Alejandro; Ruiz-Ponce, M.; Cuesta-López, Laura; Román-Rodríguez, Cristóbal; Pérez-Sánchez, C.; Ruiz-Limón, P.; Ruiz, Rocío Guzman-; Leiva-Cepas, Fernando; Seguí, Pedro; Plasencia, C.; Martínez‐Feito, Ana; Font, Pilar; Ábalos, María C.; Ortega, R.; Malagón, Marı́a M.; Tinahones, Francisco J.; Collantes-Estévez, Eduardo; López‐Pedrera, Chary; Barbarroja, Nuria

doi:10.1016/j.isci.2022.104893

Cited by 6 publications

(4 citation statements)

References 58 publications

(75 reference statements)

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“…Interestingly, in RA patients, adipose tissue macrophages and crown-like structures are more represented and associated with the pro-inflammatory process and IR [ 25 ]. In addition, the presence of ACPA was also related to IR and altered adipocytokine profile [ 26 ], further reinforcing the idea of a strict connection between RA and glucose derangement. Thus, a better comprehensive control of inflammatory process and glucose alterations may improve the therapeutic management of RA patients with T2D, since the established IR of T2D may negatively influence the response of administered therapies [ 4 , 6 , 10 ].…”

Section: Discussionmentioning

confidence: 89%

“…All these observations may suggest that the JAK/STAT signalling pathway may play a crucial role in the regulation of glucose derangement and obesity, thus suggesting its manipulation as a promising therapeutic strategy in this context. In fact, in RA patients with T2D, a possible vicious circle may be perpetuated by a rheumatoid inflammatory process, the presence of ACPA, deregulated glucose homeostasis, and adiposity [ 24 – 26 ]. RA metabolic alterations are shown to be linked with the degree of pro-inflammatory process, which may have as initial target inflammation of the adipose tissue in deregulating glucose as well as lipid homeostasis [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

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The effects of suppressing inflammation by tofacitinib may simultaneously improve glycaemic parameters and inflammatory markers in rheumatoid arthritis patients with comorbid type 2 diabetes: a proof-of-concept, open, prospective, clinical study

Di Muzio,

Di Cola,

Shariat Panahi

et al. 2024

Arthritis Res Ther

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Background A consistent connection has been increasingly reported between rheumatoid arthritis (RA), insulin resistance (IR), and type 2 diabetes (T2D). The β-cell apoptosis induced by pro-inflammatory cytokines, which could be exaggerated in the context of RA, is associated with increased expression pro-apoptotic proteins, which is dependent on JAnus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) activation. On these bases, we aimed to evaluate if the administration of tofacitinib, a potent and selective JAK inhibitor, could simultaneously improve glycaemic parameters and inflammatory markers in patients with RA and comorbid T2D. Methods The primary endpoint was the change in the 1998-updated homeostatic model assessment of IR (HOMA2-IR) after 6 months of treatment with tofacitinib in RA patients with T2D. Consecutive RA patients with T2D diagnosis were included in this proof-of-concept, open, prospective, clinical study, which was planned before the recent emergence of safety signals about tofacitinib. Additional endpoints were also assessed regarding RA disease activity and metabolic parameters. Results Forty consecutive RA patients with T2D were included (female sex 68.9%, mean age of 63.4 ± 9.9 years). During 6-month follow-up, a progressive reduction of HOMA2-IR was observed in RA patients with T2D treated with tofacitinib. Specifically, a significant effect of tofacitinib was shown on the overall reduction of HOMA2-IR (β = − 1.1, p = 0.019, 95%CI − 1.5 to − 0.76). Also, HOMA2-β enhanced in these patients highlighting an improvement of insulin sensitivity. Furthermore, although a longer follow-up is required, a trend in glycated haemoglobin reduction was also recorded. The administration of tofacitinib induced an improvement in RA disease activity, and a significant reduction of DAS28-CRP and SDAI was observed; 76.8% of patients achieved a good clinical response. In this study, no major adverse events (AEs) were retrieved without the identification of new safety signals. Specifically, no life-threatening AEs and cardiovascular and/or thromboembolic events were recorded. Conclusions The administration of tofacitinib in RA with T2D led to a simultaneous improvement of IR and inflammatory disease activity, inducing a “bidirectional” benefit in these patients. However, further specific designed and powered studies are warranted to entirely evaluate the metabolic effects of tofacitinib in RA patients with T2D.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

The effects of suppressing inflammation by tofacitinib may simultaneously improve glycaemic parameters and inflammatory markers in rheumatoid arthritis patients with comorbid type 2 diabetes: a proof-of-concept, open, prospective, clinical study

Di Muzio,

Di Cola,

Shariat Panahi

et al. 2024

Arthritis Res Ther

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“…The development of RA requires the involvement of glucose and lipid metabolism. For example, Arias-de la Rosa et al proved that metabolic disturbances associated with RA, and it is depended on the degree of inflammation and identify inflammation of adipose tissue ( 16 ); moreover, Ye et al proved that RA patients should be evaluated early for the presence of IR to reduce the risk of metabolic diseases ( 17 ). Accordingly, the primary purpose of this study was to investigate the role of the changes of peripheral blood AFU activity in glucose and lipid metabolism in RA patients.…”

Section: Introductionmentioning

confidence: 99%

Changes of peripheral blood α-L-fucosidase activity in patients with rheumatoid arthritis: a cross-sectional study

Zhou,

He,

Yuan

2024

Ann Joint

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Background Rheumatoid arthritis (RA), a systemic autoimmune disease with approximately 1% prevalent population worldwide, which the etiology is still unclear. RA cannot be completely cured at present, which seriously affects the quality of life of patients. This study is to compare the peripheral blood α-L-fucosidase (AFU) between RA and healthy persons. Methods A cross-sectional study was performed using total of 96 patients with RA served as case group and another 94 age-matched healthy volunteers served as a control group. AFU assay is detected by continuous monitoring method using Toshiba TBA-120FR (Tokyo, Japan) fully automatic biochemical analyzer in Japan, and the reagent is purchased from Zhejiang Quark Biological Company (Zhejiang, China). Statistical analysis was performed using SPSS 24.0 (SPSS, Inc., Chicago, IL, USA). Results AFU activity in peripheral blood of RA patients were lower than healthy controls. The higher AFU activity, the shorter the course of disease (r=−0.2790, P=0.0065). The activity of lactate dehydrogenase in patients with RA is higher than that of healthy control, but the activity of acetylcholinesterase is lower than that of normal people. Finally, AFU activity was negatively correlated with the activity of lactate dehydrogenase (r=−0.2381, P=0.0208) and positively correlated with the activity of acetylcholinesterase (r=0.2985, P=0.0035). Conclusions Changes of peripheral blood AFU activity might be associated with progression of disease in RA patients. The changes of AFU activity may lead to disturbances in glucose and lipid metabolism.

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“…Ademais, estudos recentes demonstram que pacientes com AR apresentam alteração na composição de gordura comparado a massa corporal, com aumento de macrófagos M1 com estrutura do tipo coroa e células B no tecido adiposo, maior sensibilidade a insulina, aumento de proteínas citrulinadas e auto-anticorpos, aumento de adipocinas como a resistina, leptina, visfatina e citocinas pró-inflamatórias, e consequente aumento da atividade da doença e DCV. Estes eventos resultam em diferenciação prejudicada dos adipócitos, com alteração no perfil celular e inflamatório, associados a resistência ao tratamento convencional, nos quais podem ser revertidos ao serem tratados com agentes biológicos(GILES et al, 2018;ARIAS-DE LA ROSA et al, 2022). Nosso estudo foi o primeiro a demonstrar a importância do PVAT para manutenção da função vascular na imunização precedente a AIA, pois as artérias com PVAT ainda mantêm a vasodilatação neste estágio da doença, além de manter seu efeito anti-contrátil.…”

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Papel da resistina via CAP1 nas alterações vasculares mediadas pelo tecido adiposo perivascular em modelo experimental de artrite reumatoide

Fedoce¹

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Primeiramente, gostaria de agradecer as agências de fomento que possibilitaram a realização deste trabalho e auxílio com a bolsa de estudo concedida. O presente trabalho foi realizado com apoio da Coordenação de Aperfeiçoamento de Pessoal de Nível Superior -Brasil (CAPES) -Código de Financiamento 001. O presente trabalho também foi realizado com apoio da Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) sob o processo número 2019/24921-4. Gostaria de agradecer a minha orientadora Prof a . Rita Tostes, no qual sempre proporcionou todo o suporte necessário para a execução deste trabalho, sejam eles materiais, profissionais ou até mesmo emocionais. Durante esta jornada, sempre demonstrou com muita humanidade o caminho da orientação e do sentido de construir o pensamento científico crítico. Agradeço também ao Prof. Mitchell A Lazar e ao Prof. Anthony Bonavia por gentilmente cederem os animais nocautes do estudo. Além, da equipe de importação do CRID e USP que auxiliaram no manejo dos animais. A Prof a Ana Paula Dantas por ter me recebido por um período em seu laboratório no August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Espanha. Muito obrigada por compartilhar tanto conhecimento e proporcionar experiências incríveis e compartilhar o laboratório com Francisco, Aline, Ana, Marta, entre tantos. Além disso, pude encontrar pessoas que me auxiliaram tecnicamente, cientificamente e pessoalmente a construir este trabalho. Ao Flávio Protássio, que sempre me motivou e acreditou na execução deste trabalho. Ao Marcos Rosa por tantas noites de citometria, muito aprendizado e amizade. A Ayda, por sempre auxiliar nas questões relacionadas a doença do estudo. A Mirelle por sempre ser amiga de laboratório e pessoal, ajudando no que fosse necessário. As outras pessoas que contribuíram para executar e além disso, tornar a ciência compartilhável. Meu muito obrigada, Isadora, Edismauro e Josiane por tantos ensinamentos. Obrigada aos Professores José Carlos F.Alves Filho e Fernando Cunha pelo suporte técnico.Aos meus companheiros de laboratório, muito obrigada por tornarem essa jornada mais leve agradável, agradeço por tantos anos

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Pathogenic mechanisms involving the interplay between adipose tissue and auto-antibodies in rheumatoid arthritis

Cited by 6 publications

References 58 publications

The effects of suppressing inflammation by tofacitinib may simultaneously improve glycaemic parameters and inflammatory markers in rheumatoid arthritis patients with comorbid type 2 diabetes: a proof-of-concept, open, prospective, clinical study

The effects of suppressing inflammation by tofacitinib may simultaneously improve glycaemic parameters and inflammatory markers in rheumatoid arthritis patients with comorbid type 2 diabetes: a proof-of-concept, open, prospective, clinical study

Changes of peripheral blood α-L-fucosidase activity in patients with rheumatoid arthritis: a cross-sectional study

Papel da resistina via CAP1 nas alterações vasculares mediadas pelo tecido adiposo perivascular em modelo experimental de artrite reumatoide

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