Article
Pharmacology & Pharmacy
Luis Sainz, Pau Riera, Patricia Moya, Sara Bernal, Jordi Casademont, Cesar Diaz-Torne, Ana Milena Millan, Hye Sang Park, Adriana Lasa, Hector Corominas
Summary: Rheumatoid arthritis (RA) is a common autoimmune disease, and Tocilizumab (TCZ) is a commonly used treatment. This study found that the genetic variant rs4845625 in the IL6R gene is associated with the response to TCZ treatment, which may help predict the treatment effect for patients.
Article
Immunology
Jose Manuel Sanchez-Maldonado, Rafael Caliz, Miguel Angel Lopez-Nevot, Antonio Jose Cabrera-Serrano, Ana Moniz-Diez, Helena Canhao, Rob Ter Horst, Luca Quartuccio, Signe B. Sorensen, Bente Glintborg, Merete L. Hetland, Ileana Filipescu, Eva Perez-Pampin, Pablo Conesa-Zamora, Jerzy Swierkot, Alfons A. den Broeder, Salvatore De Vita, Eva Rabing Brix Petersen, Yang Li, Miguel A. Ferrer, Alejandro Escudero, Mihai G. Netea, Marieke J. H. Coenen, Vibeke Andersen, Joao E. Fonseca, Manuel Jurado, Katarzyna Bogunia-Kubik, Eduardo Collantes, Juan Sainz
Summary: This study confirmed the influence of the LINC02549 and LRRC55 loci on determining the response to TNFi in RA patients, while suggesting a weak effect of the MAFB and CNTN5 loci that require further investigation.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Genetics & Heredity
Shicheng Guo, Yehua Jin, Jieru Zhou, Qi Zhu, Ting Jiang, Yanqin Bian, Runrun Zhang, Cen Chang, Lingxia Xu, Jie Shen, Xinchun Zheng, Yi Shen, Yingying Qin, Jihong Chen, Xiaorong Tang, Peng Cheng, Qin Ding, Yuanyuan Zhang, Jia Liu, Qingqing Cheng, Mengru Guo, Zhaoyi Liu, Weifang Qiu, Yi Qian, Yang Sun, Yu Shen, Hong Nie, Steven J. Schrodi, Dongyi He
Summary: Genome-wide association studies have identified over 100 genetic risk factors for rheumatoid arthritis, but they can only explain less than 40% of its heritability. To address the missing heritability, novel functional SNPs were identified through genotyping HLA SNPs and common SNPs located in miRNA. The study discovered new SNPs significantly associated with rheumatoid arthritis and demonstrated significant epistasis effects between certain SNPs.
FRONTIERS IN GENETICS
(2021)
Article
Genetics & Heredity
Yasir Ali, Yangchao Chen, Zia Ul Islam, Aisha Aman, Mashal M. Almutairi, Abdulaziz Alouffi, Aymen Mohammed, Aftab Ali Shah, Zia Ur Rehman, Ibrar Hussain, Abid Ali, Fazal Jalil
Summary: This study aimed to investigate the association of single nucleotide variants with rheumatoid arthritis (RA) in the Pakistani population. The researchers recruited and genotyped 600 individuals and found a significant association of rs2292832 in MIR149 and rs3746444 in MIR499 with RA.
Article
Medicine, Research & Experimental
Yu Cao, Ying Yang, Qingfeng Hu, Guojun Wei
Summary: This study identifies seven potential drug targets for RA through Mendelian randomization (MR) analysis, with support from two independent cohorts. These genes are strongly associated with immune function in terms of biological significance. Drug prediction and molecular docking further validate the medicinal value of these targets.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Medicine, General & Internal
Xiaoli Liu, Linna Peng, Dandan Li, Chunjuan He, Shishi Xing, Yuhe Wang, Yongjun He
Summary: Certain genetic variants of IL1R1 and IL1R2 were found to be associated with the susceptibility to rheumatoid arthritis (RA) in the Chinese Han population in this study.
INTERNATIONAL JOURNAL OF GENERAL MEDICINE
(2021)
Article
Rheumatology
Haruka Tsuchiya, Mineto Ota, Shuji Sumitomo, Kazuyoshi Ishigaki, Akari Suzuki, Toyonori Sakata, Yumi Tsuchida, Hiroshi Inui, Jun Hirose, Yuta Kochi, Yuho Kadono, Katsuhiko Shirahige, Sakae Tanaka, Kazuhiko Yamamoto, Keishi Fujio
Summary: Objectives: Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation in the synovium, where synovial fibroblasts (SFs) play a major role. This study aimed to understand the genetic contribution to molecular regulatory networks in SFs under inflammatory conditions. Methods: SFs from RA and osteoarthritis (OA) patients were stimulated with various cytokines and immune cell subsets were analyzed. Integrative analyses including mRNA expression, histone modifications, 3D genome architecture, and genetic variations were performed. Results: Unstimulated SFs from RA patients showed differences in transcriptome and epigenome compared to OA SFs. Most responses to stimulations were shared between the diseases. SFs expressed pathogenic genes and chromatin remodeling in activated SFs revealed enrichment of RA risk loci in clusters of enhancers induced by proinflammatory cytokines. A RA risk SNP formed 3D contact with the promoter of a gene related to arthritis, and inhibition of this gene suppressed cytokine and chemokine production in SFs. Conclusions: This study identified potential therapeutic targets associated with genetic risk of RA and established a dynamic landscape of activated SFs.
ANNALS OF THE RHEUMATIC DISEASES
(2021)
Article
Biochemistry & Molecular Biology
Ana Triguero-Martinez, Emilia Roy-Vallejo, Nuria Montes, Hortensia de la Fuente, Ana Maria Ortiz, Santos Castaneda, Isidoro Gonzalez-Alvaro, Amalia Lamana
Summary: A study found that genetic variants in the LGALS1 gene are associated with Gal1 serum levels, and these genetic variants can explain the differences in Gal1 levels among patients, with higher levels of Gal1 being associated with lower levels of IL-6.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, General & Internal
Lin-Lin Zhang, Xiao-Xiao Wu, Xu-Fan Wang, Dong-Sheng Di, Qian Huang, Rui-Shan Liu, Zong-Wen Shuai, Dong-Qing Ye, Rui-Xue Leng
Summary: The study investigated the association between SNPs in the miR-146a gene and susceptibility of RA, finding that the SNP rs2431697 in miR-146a gene is associated with RA risk. The effect size of this SNP was larger in Asian population compared to European population. Plasma TNF-alpha levels in healthy controls were inversely associated with the risk allele T of the SNP rs2431697.
ANNALS OF MEDICINE
(2021)
Article
Orthopedics
Youguo Hao, Lijun Xie, Jing Xia, Zhen Liu, Baoxiu Yang, Minqin Zhang
Summary: The study revealed that IL-21 plays a crucial role in the pathogenesis of rheumatoid arthritis (RA), with the rs2055979 polymorphism of IL-21 associated with IL-21 plasma levels and predisposition to RA development in the Chinese population. Elevated plasma IL-21 levels were found in RA patients, indicating a positive correlation with disease severity.
BMC MUSCULOSKELETAL DISORDERS
(2021)
Article
Health Care Sciences & Services
Alaa S. Wahba, Maha E. Ibrahim, Dina M. Abo-elmatty, Eman T. Mehanna
Summary: This study demonstrated that adipokines chemerin and vaspin were elevated in patients with rheumatoid arthritis, while apelin and omentin levels were lower. Specific genetic variants of chemerin, vaspin, and omentin were associated with increased susceptibility to RA.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Review
Immunology
Cen Chang, Lingxia Xu, Runrun Zhang, Yehua Jin, Ping Jiang, Kai Wei, Linshuai Xu, Yiming Shi, Jianan Zhao, Momiao Xiong, Shicheng Guo, Dongyi He
Summary: MicroRNAs (miRNAs) play crucial roles in the pathogenesis, diagnosis, and therapeutic intervention of rheumatoid arthritis (RA). They regulate gene expression, immune system differentiation, and serve as potential biomarkers and therapeutic targets.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Medicine, General & Internal
Chia-Chun Tseng, Yuan-Zhao Lin, Chia-Hui Lin, Daw-Yang Hwang, Ruei-Nian Li, Wen-Chan Tsai, Tsan-Teng Ou, Cheng-Chin Wu, Yu-Chih Lin, Wan-Yu Sung, Kuan-Yu Chen, Shun-Jen Chang, Jeng-Hsien Yen
Summary: This study found that CREM hypomethylation and upregulation occur in rheumatoid arthritis (RA), and CREM variants are associated with the development of serositis and lymphadenopathy in RA.
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
(2022)
Editorial Material
Rheumatology
Ana C. Medeiros-Ribeiro, Nadia E. Aikawa
Summary: Patients with autoimmune rheumatic disease on methotrexate therapy exhibit poor immune response to vaccines, including those for COVID-19. Emerging evidence suggests temporarily discontinuing this treatment to improve immunogenicity.
NATURE REVIEWS RHEUMATOLOGY
(2022)
Article
Rheumatology
Luis Sainz, Pau Riera, Patricia Moya, Sara Bernal, Jordi Casademont, Cesar Diaz-Torne, Ana Milena Millan, Hye Sang Park, Adriana Lasa, Hector Corominas
Summary: A retrospective cohort study of 62 patients treated with Sarilumab found that SNPs in the IL6R gene may predict efficacy and toxicity responses. Specifically, three SNPs were significantly associated with response outcomes.
ARTHRITIS RESEARCH & THERAPY
(2023)
Article
Nutrition & Dietetics
Nuno M. P. Mendonca, Linda M. Hengeveld, Nancy Presse, Helena Canhao, Eleanor Simonsick, Stephen B. Kritchevsky, Samaneh Farsijani, Pierrette Gaudreau, Carol Jagger, Marjolein Visser
Summary: This study aimed to investigate the relationship between protein intake and grip strength, as well as the interaction between protein intake and physical activity, in relation to the rate of grip strength decline in older adults. The findings showed no evidence to support the hypothesis that higher protein intake, alone or in combination with higher physical activity, slowed the rate of grip strength decline in older adults.
BRITISH JOURNAL OF NUTRITION
(2023)
Article
Oncology
Marco Dicanio, Matteo Giaccherini, Alyssa Clay-Gilmour, Angelica Macauda, Juan Sainz, Mitchell J. Machiela, Malwina Rybicka-Ramos, Aaron D. Norman, Agata Tyczynska, Stephen J. Chanock, Torben Barington, Shaji K. Kumar, Parveen Bhatti, Wendy Cozen, Elizabeth E. Brown, Anna Suska, Eva K. Haastrup, Robert Z. Orlowski, Marek Dudzinski, Ramon Garcia-Sanz, Marcin Kruszewski, Joaquin Martinez-Lopez, Katia Beider, Elzbieta Iskierka-Jazdzewska, Matteo Pelosini, Sonja Berndt, Malgorzata Razny, Krzysztof Jamroziak, S. Vincent Rajkumar, Artur Jurczyszyn, Annette Juul Vangsted, Pilar Garrido Collado, Ulla Vogel, Jonathan N. Hofmann, Mario Petrini, Aleksandra Butrym, Susan L. Slager, Elad Ziv, Edyta Subocz, Graham G. Giles, Niels Frost Andersen, Grzegorz Mazur, Marzena Watek, Fabienne Lesueur, Michelle A. T. Hildebrandt, Daria Zawirska, Lene Hyldahl Ebbesen, Herlander Marques, Federica Gemignani, Charles Dumontet, Judit Varkonyi, Gabriele Buda, Arnon Nagler, Agnieszka Druzd-Sitek, Xifeng Wu, Katalin Kadar, Nicola J. Camp, Norbert Grzasko, Rosalie G. Waller, Celine Vachon, Federico Canzian, Daniele Campa
Summary: The aim of this study was to identify novel pleiotropic variants involved in multiple myeloma (MM) risk. Through analysis of 28,684 single nucleotide polymorphisms (SNPs), DNAJB4-rs34517439-A was found to be associated with an increased risk of developing MM.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Health Care Sciences & Services
Helena Santos, Ana Rita Henriques, Jaime Branco, Pedro M. Machado, Helena Canhao, Fernando M. Pimentel-Santos, Ana Maria Rodrigues
Summary: The study found that both spondyloarthritis and chronic low back pain have similar impacts on health-related quality of life (HRQoL), including mental, physical, and social domains. Patients with spondyloarthritis and chronic low back pain reported significantly lower HRQoL compared to those without rheumatic diseases. Modifiable factors such as multimorbidity, active disease, obesity, and regular physical exercise were associated with HRQoL in these conditions.
QUALITY OF LIFE RESEARCH
(2023)
Article
Hematology
Juan Jose Rodriguez-Sevilla, Concepcion Fernandez-Rodriguez, Leyre Bento, Ramon Diez-Feijoo, Sergio Pinzon, Joan Gibert, Lierni Fernandez-Ibarrondo, Marta Lafuente, Ana Ferrer, Blanca Sanchez-Gonzalez, Eva Gimeno, Juan Sainz, Rafael Ramos, Juan F. Garcia, Lluis Colomo, Beatriz Bellosillo, Antonio Gutierrez, Antonio Salar
Summary: Four clinical or clinicogenetic-risk models were explored in patients with symptomatic FL who received frontline immunochemotherapy. The FLIPI remains the clinical risk score with higher discrimination in patients with advanced FL treated with immunochemotherapy, but the performance of the m7-FLIPI should be further investigated in patients treated with R-B.
Article
Orthopedics
Daniela Costa, Eduardo B. Cruz, David G. Lopes, Catarina Nunes da Silva, Ana Rita Henriques, Diogo Luis, Jaime Branco, Helena Canhao, Ana M. Rodrigues
Summary: Pain due to knee and/or hip osteoarthritis is a common reason for seeking healthcare. This study aimed to estimate the prevalence of unmanageable pain levels among people with osteoarthritis, identify factors associated with unmanageable pain, and compare therapeutic strategies used by individuals with unmanageable pain versus manageable pain.
BMC MUSCULOSKELETAL DISORDERS
(2023)
Article
Medicine, General & Internal
Joao Pedro Ferreira, Adelino Leite-Moreira, Altamiro da Costa-Pereira, Antonio Jose Soares, Carlos Robalo-Cordeiro, Carmen Jeronimo, Cristina Gavina, Fausto J. Pinto, Fernando Schmitt, Francisca Saraiva, Francisco Vasques-Novoa, Helena Canhao, Henrique Cyrne-Carvalho, Isabel Palmeirim, Joana Pimenta, Joao Eurico Cabral Da Fonseca, Joao Firmino-Machado, Jorge Correia Pinto, Lino Goncalves, Miguel Castelo Branco, Nuno Sousa, Ricardo Fontes de Carvalho, Teresa Machado Luciano, Tiago Gil Oliveira, Catarina Resende Oliveira
Summary: Portugal has a chronic problem of underfunding in scientific research. Despite increasing national investment in recent years, it is still significantly insufficient. Clinical medicine, immunology, and multicenter epidemiological and cohort studies, which have huge potential for return on investment in clinical trials, are not given priority in the National Health Plan in Portugal, and researcher initiated studies in these fields are underfunded.
ACTA MEDICA PORTUGUESA
(2023)
Article
Biochemistry & Molecular Biology
Jose Manuel Sanchez-Maldonado, Antonio Jose Cabrera-Serrano, Subhayan Chattopadhyay, Daniele Campa, Maria del Pilar Garrido, Angelica Macauda, Rob Ter Horst, Andres Jerez, Mihai G. G. Netea, Yang Li, Kari Hemminki, Federico Canzian, Asta Foersti, Juan Sainz
Summary: This study found that obesity-related genetic variants do not impact the risk of developing MM, based on genomic association studies conducted in German and Spanish populations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Antonio Jose Cabrera-Serrano, Jose Manuel Sanchez-Maldonado, Rob ter Horst, Angelica Macauda, Paloma Garcia-Martin, Yolanda Benavente, Stefano Landi, Alyssa Clay-Gilmour, Yasmeen Niazi, Blanca Espinet, Juan Jose Rodriguez-Sevilla, Eva Maria Perez, Rossana Maffei, Gonzalo Blanco, Matteo Giaccherini, James R. Cerhan, Roberto Marasca, Miguel Angel Lopez-Nevot, Tzu Chen-Liang, Hauke Thomsen, Irene Gamez, Daniele Campa, Victor Moreno, Silvia de Sanjose, Rafael Marcos-Gragera, Maria Garcia-Alvarez, Trinidad Dierssen-Sotos, Andres Jerez, Aleksandra Butrym, Aaron D. Norman, Mario Luppi, Susan L. Slager, Kari Hemminki, Yang Li, Sonja I. Berndt, Delphine Casabonne, Miguel Alcoceba, Anna Puiggros, Mihai G. Netea, Asta Foersti, Federico Canzian, Juan Sainz
Summary: Chronic lymphocytic leukemia (CLL) is the most common leukemia among adults worldwide. However, a study found that the GWAS-identified risk variants for CLL do not significantly impact overall survival and disease progression in CLL patients. The polygenic risk scores (PRSs) built with these risk variants also have limited accuracy in predicting patient survival and disease progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Luis Antunes Gomes, Ana Maria Rodrigues, Jaime Branco, Helena Canhao, Eduardo Brazete Cruz
Summary: This study aimed to investigate the courses of chronic low back pain (CLBP), its cumulative impact, and the indicators for the persistence of pain. The results showed that patients with CLBP could follow a persistent or relapsing course of pain in the long-term. Being female, presenting depressive symptoms, having a manual job, and higher disability at baseline were predictors of a persistent course of LBP.
Article
Cell & Tissue Engineering
Sara Reis Moura, Jaime Freitas, Claudia Ribeiro-Machado, Jorge Lopes, Nuno Neves, Helena Canhao, Ana Maria Rodrigues, Mario Adolfo Barbosa, Maria Ines Almeida
Summary: This study decodes the regulatory network of the lncRNA H19 on the extracellular matrix (ECM) and reveals its impact on bone regeneration. Inhibition of H19 expression results in decreased ECM density and collagen content, and promotes adipogenic differentiation of bone marrow-derived stem cells. Furthermore, H19 is targeted by miR-29c, which is downregulated in osteoporotic bone tissue and affects MSC proliferation and collagen production. These findings suggest that H19 is a potential therapeutic target for controlling cell behavior and engineering the bone ECM.
STEM CELL RESEARCH & THERAPY
(2023)
Article
Medicine, General & Internal
Claudia M. M. Munoz-Herrera, Juan Francisco Gutierrez-Bautista, Miguel Angel Lopez-Nevot
Summary: This study evaluated the association between complement-fixing dnDSA antibodies and graft loss, as well as the possible association between non-complement-fixing antibodies and transplanted organ survival in kidney transplant recipients. The presence of C1q-binding dnDSA was significantly associated with rejection frequency and renal graft loss. These findings suggest that classifying dnDSA based on their ability to activate the complement and detecting complement-binding capacity could serve as prognostic markers for predicting AMR outcome and graft survival in kidney transplant patients who develop dnDSA.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Medicine, General & Internal
I Arias-de la Rosa, M. Ruiz-Ponce, L. Cuesta-Lopez, C. Perez-Sanchez, F. Leiva-Cepas, Md Gahete, P. Navarro, R. Ortega, J. Cordoba, E. Perez-Pampin, A. Gonzalez, A. J. Lucendo, E. Collantes-Estevez, Ch Lopez-Pedrera, A. Escudero-Contreras, N. Barbarroja
Summary: Rheumatoid arthritis patients may experience mild to moderate liver inflammation due to the infiltration of T, B cells, and macrophages, as well as the action of anticitrullinated protein antibodies (ACPAs). This phenomenon is independent of obesity or diabetes and is associated with systemic inflammation and disease activity levels.
EUROPEAN JOURNAL OF INTERNAL MEDICINE
(2023)
Letter
Rheumatology
Clementina Lopez-Medina, Antonio Doblas, Alejandro Escudero-Contreras, Eduardo Collantes-Estevez
JOURNAL OF RHEUMATOLOGY
(2023)
Article
Rheumatology
Helena Santos, Ana R. Henriques, Pedro M. Machado, Clementina Lopez-Medina, Maxime Dougados, Helena Canhao, Ana M. Rodrigues, Fernando Pimentel-Santos
Summary: The study identifies the determinants of health-related quality of life and global functioning and health in patients with axial SpA, peripheral SpA, and PsA. Disease activity and physical function were found to be major factors influencing HRQoL and GH across different types of SpA. Clinical characteristics and sociodemographic factors also play an important role, highlighting the importance of a holistic approach for individual patients.
Article
Rheumatology
David G. Lopes, Daniela Costa, Eduardo B. Cruz, Nuno Mendonca, Ana Rita Henriques, Jaime Branco, Helena Canhao, Ana M. Rodrigues
Summary: This study analyzed the impact of long-term physical activity on physical function and health-related quality of life in patients with hip and knee osteoarthritis. The results showed that frequent and very frequent physical activity were associated with improved physical function and health-related quality of life over time. These findings emphasize the importance of maintaining regular physical activity to optimize quality of life and physical function.
ARTHRITIS RESEARCH & THERAPY
(2023)