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1. NT-proBNP and sRAGE levels in early rheumatoid arthritis

Author

UMC Utrecht Holding, MS Reumatologie/Immunologie/Infectie, Infection & Immunity, Regenerative Medicine and Stem Cells, Heslinga, M., Teunissen, C., Agca, R., van der Woude, D., Huizinga, T. W.J., van Laar, J., den Broeder, A., Lems, W., Nurmohamed, M., UMC Utrecht Holding, MS Reumatologie/Immunologie/Infectie, Infection & Immunity, Regenerative Medicine and Stem Cells, Heslinga, M., Teunissen, C., Agca, R., van der Woude, D., Huizinga, T. W.J., van Laar, J., den Broeder, A., Lems, W., and Nurmohamed, M.

Published
2023

2. NT-proBNP and sRAGE levels in early rheumatoid arthritis

Author

Heslinga, M., Teunissen, C., Agca, R., Woude, D. van der, Huizinga, T., Laar, J. van, Broeder, A. den, Lems, W., Nurmohamed, M., Heslinga, M., Teunissen, C., Agca, R., Woude, D. van der, Huizinga, T., Laar, J. van, Broeder, A. den, Lems, W., and Nurmohamed, M.

Abstract

Item does not contain fulltext, OBJECTIVE: Several biomarkers of cardiovascular function are found to be increased in rheumatoid arthritis (RA), with some suggesting a relationship with disease activity and improvement with adequate anti-rheumatic treatment. Promising biomarkers include N-terminal pro-brain natriuretic peptide (NT-proBNP) and the soluble receptor form of advanced glycation end-products (sRAGE). The objective of this study was to investigate associations between NT-proBNP and sRAGE levels and markers of inflammation and disease activity in early RA patients and their changes during (effective) anti-rheumatic treatment. METHOD: Data from 342 consecutive early RA patients participating in the 'Parelsnoer' cohort were used. At baseline and after 6 months' disease activity, NT-proBNP and sRAGE levels were assessed. RESULTS: After 6 months, NT-proBNP decreased from 83 pmol/L (mean) at baseline to 69 pmol/L at follow-up (p < 0.001), while sRAGE increased from 997 pg/mL to 1125 pg/mL (p < 0.001). A larger decrease in erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) was associated with larger changes in NT-proBNP and sRAGE. For every point decrease in ESR, there was a 1.7-point decrease in NT-proBNP and a 2.2-point increase in sRAGE. For CRP, these values were 1.7 and 2.7, respectively (p < 0.001). CONCLUSION: Suppressing inflammation, independently of achieving remission, increases sRAGE levels and decreases NT-proBNP levels significantly. Whether this translates into a decrease in incident cardiovascular disease remains to be elucidated.

Published
2023

3. One year in review 2020: novelties in the treatment of rheumatoid arthritis

Author

Silvagni, E, Giollo, A, Sakellariou, G, Ughi, N, D'Amico, M, Scire, C, Huizinga, T, Silvagni E., Giollo A., Sakellariou G., Ughi N., D'Amico M. E., Scire C. A., Huizinga T. W. J., Silvagni, E, Giollo, A, Sakellariou, G, Ughi, N, D'Amico, M, Scire, C, Huizinga, T, Silvagni E., Giollo A., Sakellariou G., Ughi N., D'Amico M. E., Scire C. A., and Huizinga T. W. J.

Abstract

Rheumatoid arthritis (RA) management is driven by evidence, and new 2019 EULAR recommendations help in refining the relevant place of different disease-modifying anti-rheumatic drugs (DMARDs) in treatment schedules. At present, new drugs are in phase of development, mainly Janus Kinase inhibitors (JAKis), however, specific treatment strategies seem to count more than individual DMARDs in terms of treatment responses, given the substantial lack of head-to-head comparisons between specific biological (b) and targeted synthetic (ts)DMARDs, and with the general perception of a similar efficacy profile across drugs. In this setting, when reliable biomarkers able to predict treatment responses are lacking, treatment decisions are mainly driven by specific clinical or individual factors, given the recognised role of comorbidities, treatment-specific side effects, patients’ preferences, and costs on drug choice. In this narrative review, the authors give their specific point of view on the management of RA, based on a critical revision of the literature published in 2019, focusing on relevant novelties and future research directions.

Published
2020

4. One year in review 2020: novelties in the treatment of rheumatoid arthritis

Author

Silvagni, E, Giollo, A, Sakellariou, G, Ughi, N, D'Amico, M, Scire, C, Huizinga, T, Silvagni E., Giollo A., Sakellariou G., Ughi N., D'Amico M. E., Scire C. A., Huizinga T. W. J., Silvagni, E, Giollo, A, Sakellariou, G, Ughi, N, D'Amico, M, Scire, C, Huizinga, T, Silvagni E., Giollo A., Sakellariou G., Ughi N., D'Amico M. E., Scire C. A., and Huizinga T. W. J.

Abstract

Rheumatoid arthritis (RA) management is driven by evidence, and new 2019 EULAR recommendations help in refining the relevant place of different disease-modifying anti-rheumatic drugs (DMARDs) in treatment schedules. At present, new drugs are in phase of development, mainly Janus Kinase inhibitors (JAKis), however, specific treatment strategies seem to count more than individual DMARDs in terms of treatment responses, given the substantial lack of head-to-head comparisons between specific biological (b) and targeted synthetic (ts)DMARDs, and with the general perception of a similar efficacy profile across drugs. In this setting, when reliable biomarkers able to predict treatment responses are lacking, treatment decisions are mainly driven by specific clinical or individual factors, given the recognised role of comorbidities, treatment-specific side effects, patients’ preferences, and costs on drug choice. In this narrative review, the authors give their specific point of view on the management of RA, based on a critical revision of the literature published in 2019, focusing on relevant novelties and future research directions.

Published
2020

5. Integrated Cryo-CMOS Temperature Sensors for Quantum Control ICs

Author

't Hart, P.A. (author), Huizinga, T. (author), Babaie, M. (author), Vladimirescu, A. (author), Sebastiano, F. (author), 't Hart, P.A. (author), Huizinga, T. (author), Babaie, M. (author), Vladimirescu, A. (author), and Sebastiano, F. (author)

Abstract

This work presents an experimental study of different components (resistors, diodes, transistors) in a standard 40-nm bulk CMOS process for their suitability as integrated cryogenic temperature sensors down to a temperature of 4.2K. It was found that most devices can be employed as sensors down to temperatures of approximately 50K, below which non-ideal effects such as non-linear behaviour and decreased sensitivity start to dominate. The Dynamic-Threshold MOS (DTMOS) was found to be a very promising candidate for its linearity, low forward-voltage-drop and sensitivity down to 8K. Moreover, as previous research indicated that cryogenic self-heating raises the local chip temperature to tens of Kelvins already at moderate power levels, the aforementioned sensing limitations at very low temperatures are expected to be of less importance in realistic applications. The results presented in this work contribute to the further integration of classical cryo-CMOS control electronics and qubits, towards a fully scalable quantum computer., Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public., QCD/Sebastiano Lab, Electronics, Quantum Circuit Architectures and Technology

Published
2022
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6. Validation of the adjusted multi-biomarker disease activity score as a prognostic test for radiographic progression in rheumatoid arthritis:a combined analysis of multiple studies

Author

Curtis, Jeffrey R., Weinblatt, Michael E., Shadick, Nancy A., Brahe, Cecilie H., Østergaard, Mikkel, Hetland, Merete Lund, Saevarsdottir, Saedis, Horton, Megan, Mabey, Brent, Flake, Darl D., Ben-Shachar, Rotem, Sasso, Eric H., Huizinga, T. W., Curtis, Jeffrey R., Weinblatt, Michael E., Shadick, Nancy A., Brahe, Cecilie H., Østergaard, Mikkel, Hetland, Merete Lund, Saevarsdottir, Saedis, Horton, Megan, Mabey, Brent, Flake, Darl D., Ben-Shachar, Rotem, Sasso, Eric H., and Huizinga, T. W.

Abstract

Background: The multi-biomarker disease activity (MBDA) test measures 12 serum protein biomarkers to quantify disease activity in RA patients. A newer version of the MBDA score, adjusted for age, sex, and adiposity, has been validated in two cohorts (OPERA and BRASS) for predicting risk for radiographic progression. We now extend these findings with additional cohorts to further validate the adjusted MBDA score as a predictor of radiographic progression risk and compare its performance with that of other risk factors. Methods: Four cohorts were analyzed: the BRASS and Leiden registries and the OPERA and SWEFOT studies (total N = 953). Treatments included conventional DMARDs and anti-TNFs. Associations of radiographic progression (ΔTSS) per year with the adjusted MBDA score, seropositivity, and clinical measures were evaluated using linear and logistic regression. The adjusted MBDA score was (1) validated in Leiden and SWEFOT, (2) compared with other measures in all four cohorts, and (3) used to generate curves for predicting risk of radiographic progression. Results: Univariable and bivariable analyses validated the adjusted MBDA score and found it to be the strongest, independent predicator of radiographic progression (ΔTSS > 5) compared with seropositivity (rheumatoid factor and/or anti-CCP), baseline TSS, DAS28-CRP, CRP SJC, or CDAI. Neither DAS28-CRP, CDAI, SJC, nor CRP added significant information to the adjusted MBDA score as a predictor, and the frequency of radiographic progression agreed with the adjusted MBDA score when it was discordant with these measures. The rate of progression (ΔTSS > 5) increased from < 2% in the low (1–29) adjusted MBDA category to 16% in the high (45–100) category. A modeled risk curve indicated that risk increased continuously, exceeding 40% for the highest adjusted MBDA scores. Conclusion: The adjusted MBDA score was validated as an RA disease activity measure that is prognostic for radiographic progression. The adju

Published
2021

9. The comparative responsiveness of Hospital Universitario Princesa Index and other composite indices for assessing rheumatoid arthritis activity

Author

Gonzalez-Alvaro, Isidoro, Castrejon, Isabel, Carmona, Loreto, Dougados, M., Huizinga, T., Abu Shakra, M., Alberts, A., Alperi Lopez, M., Amital, H., Aringer, M., Aslanidis, S., Berenbaum, F., Bijlsma, H., Blanco Garcia, F. J., Bliddal, H., Borofsky, M., Brocq, O., Buldakov, S., Cantini, F., Carreno Perez, L., Chahade, W., Ciconelli, R., Codreanu, C., Dahlqvist, S. R., Damjanov, N., Diamantopoulos, A., Dimdina, L., Dimic, A., Dorokhov, A., Dubikov, A., Fadienko, G., Fano, N., Ferreira, G., Gabrielli, A., Gaffney, K., Gaudin, P., Gerlag, D. M., Gerli, R., Goncalves, C. R., Hansen, M. S., Hanvivadhanakul, P., Hoili, C., Hou, A., Hunter, J., Ilic, T., Ionescu, R., Kaine, J., Kakurina, N., Kamalova, R., Kelly, T., Knyazeva, L., Krumina, L., Kurthen, R., Lagrone, R. P., Lapadula, G., Lavrentjevs, V, Lawson, J. G., Lazic, Z., Lejnieks, A., Levy, Y., Lexberg, A., Mader, R., Mariette, X., Markovits, D., Mola, Martin E., Maugars, Y., Guarch, Maymo J., Mazurov, V., I, Mikkelsen, K., Vergles, Morovic J., Nabizadeh, S., Nanagara, R., Nasonov, E. L., Sarabia, Navarro F., Neumann, T., Novak, S., Olech, E., Oza, M., Paran, D., Parsik, E., Pegram, S., Suarez, Pombo M., Popova, T., Puechal, X., Raja, N., Ridley, D., Rosner, I, Rubbert-Roth, A., Rudin, A., Saraux, A., Saulite-Kandevica, D., Settas, L., Sfikakis, P., Sheeran, T., Sizikov, A., Stamenkovic, D., Stefanovic, D., Stolow, J. B., Tan, A. L., Tebib, J., Tishler, M., Tony, H. P., Troum, O. M., Uaratanawong, S., Ucar Angulo, E., Valenzuela, G., van der Laken, K., Van Laar, J., van Riel, P. L. C. M., Vasilopoulos, D., Veldi, T., Vinogradova, I, Vosse, D., Wassenberg, S., Weidmann, C., Weitz, M., Wollenhaupt, J., Xavier, R., Yakupova, S., Zagar, I, Zavgorodnaja, T., Zemerova, E., Zisman, D., Zonova, E., Camona, Loreto, Abasolo Alcazar, L., Alegre de Miguel, C., Andreu Sanchez, J. L., Aragon Diez, A., Balsa Criado, A., Batlle Gualda, E., Belmonte Serrano, M. A., Beltran Audera, J., Beltran Fabregat, J., Bonilla Hernan, G., Caro Fernandez, N., Casado, E., Cebrian Mendez, L., Corteguera Coro, M., Cuadra Diaz, J. L., Cuesta, E., Fiter Areste, J., Freire Gonzalez, M., Galindo Izquierdo, M., Garcia Meijide, J. A., Garcia Gomez, M. C., Gimenez Ubeda, E., Gomez Centeno, E., Gomez Vaquero, C., Gonzalez Fernandez, M. J., Gonzalez Gomez, M. L., Gonzalez Hernandez, T., Gonzalez-Alvaro, I, Gonzalez-Montagut Gomez, C., Grandal Delgado, Y., Gratacos Masmitja, J., Hernandez del Rio, A., Instxaurbe, A. R., Irigoyen Oyarzabal, M., V, Jimenez Palop, M., Juan Mas, A., Judez Navarro, E., Larrosa Padro, M., Lopez Longo, F. J., Loza Santamaria, E., Maese Manzano, J., Manero Ruiz, F. J., Mateo Bernardo, I, Mayordomo Gonzalez, L., Mazzucheli, R., Medrano San Idelfonso, M., Naranjo Hernandez, A., Pecondon Espanol, A., Peiro Callizo, E., Quiros Donate, J., Ramos Lopez, P., Rivera Redondo, J., Rodriguez Gomez, M., Rodriguez Lopez, M., Rosello Pardo, R., Sampedro Alvarez, J., Sanmarti Sala, R., Rey Rey, Santos J., Tena Marsa, X., Tenorio Martin, M., Torres Martin, M. C., Urena Garnica, I, Valdazo de Diego, J. P., Valls, M., Villaverde Garcia, V., Zarco Montejo, P., Zubieta Tabernero, J., Balsa, Alejandro, Sanmarti, Raimon, Cabezas, J. A., Cantalejo, M., Chamizo, E., Ciruelo, E., Corrales, A., Cruz, A., Diaz, C., Fiter, J., Freire, M. M., Galindo, M., Garcia de Vicuna, M. R., Gelman, S. M., Gonzalez Crespo, R., Gonzalez Fernandez, C., Gracia, A., Granados, J., Guzman, M. A., Irigoyen, M., V, Juan, A., Juanola, X., Laiz, A., Manero, F. J., Martinez, A., Martinez, F., Mata, C., Maymo, J., Navarro, F. J., Peiro, E., Perez, F., Perez, G., Perez, M., Pujol, M., Quiros, J., Ribas, B., Riera, M., Rivera, J., Rodriguez, J. M., Rosello, R., Tenorio, M., Toyos, F. J., Gonzalez-Alvaro, Isidoro, Castrejon, Isabel, Carmona, Loreto, Dougados, M., Huizinga, T., Abu Shakra, M., Alberts, A., Alperi Lopez, M., Amital, H., Aringer, M., Aslanidis, S., Berenbaum, F., Bijlsma, H., Blanco Garcia, F. J., Bliddal, H., Borofsky, M., Brocq, O., Buldakov, S., Cantini, F., Carreno Perez, L., Chahade, W., Ciconelli, R., Codreanu, C., Dahlqvist, S. R., Damjanov, N., Diamantopoulos, A., Dimdina, L., Dimic, A., Dorokhov, A., Dubikov, A., Fadienko, G., Fano, N., Ferreira, G., Gabrielli, A., Gaffney, K., Gaudin, P., Gerlag, D. M., Gerli, R., Goncalves, C. R., Hansen, M. S., Hanvivadhanakul, P., Hoili, C., Hou, A., Hunter, J., Ilic, T., Ionescu, R., Kaine, J., Kakurina, N., Kamalova, R., Kelly, T., Knyazeva, L., Krumina, L., Kurthen, R., Lagrone, R. P., Lapadula, G., Lavrentjevs, V, Lawson, J. G., Lazic, Z., Lejnieks, A., Levy, Y., Lexberg, A., Mader, R., Mariette, X., Markovits, D., Mola, Martin E., Maugars, Y., Guarch, Maymo J., Mazurov, V., I, Mikkelsen, K., Vergles, Morovic J., Nabizadeh, S., Nanagara, R., Nasonov, E. L., Sarabia, Navarro F., Neumann, T., Novak, S., Olech, E., Oza, M., Paran, D., Parsik, E., Pegram, S., Suarez, Pombo M., Popova, T., Puechal, X., Raja, N., Ridley, D., Rosner, I, Rubbert-Roth, A., Rudin, A., Saraux, A., Saulite-Kandevica, D., Settas, L., Sfikakis, P., Sheeran, T., Sizikov, A., Stamenkovic, D., Stefanovic, D., Stolow, J. B., Tan, A. L., Tebib, J., Tishler, M., Tony, H. P., Troum, O. M., Uaratanawong, S., Ucar Angulo, E., Valenzuela, G., van der Laken, K., Van Laar, J., van Riel, P. L. C. M., Vasilopoulos, D., Veldi, T., Vinogradova, I, Vosse, D., Wassenberg, S., Weidmann, C., Weitz, M., Wollenhaupt, J., Xavier, R., Yakupova, S., Zagar, I, Zavgorodnaja, T., Zemerova, E., Zisman, D., Zonova, E., Camona, Loreto, Abasolo Alcazar, L., Alegre de Miguel, C., Andreu Sanchez, J. L., Aragon Diez, A., Balsa Criado, A., Batlle Gualda, E., Belmonte Serrano, M. A., Beltran Audera, J., Beltran Fabregat, J., Bonilla Hernan, G., Caro Fernandez, N., Casado, E., Cebrian Mendez, L., Corteguera Coro, M., Cuadra Diaz, J. L., Cuesta, E., Fiter Areste, J., Freire Gonzalez, M., Galindo Izquierdo, M., Garcia Meijide, J. A., Garcia Gomez, M. C., Gimenez Ubeda, E., Gomez Centeno, E., Gomez Vaquero, C., Gonzalez Fernandez, M. J., Gonzalez Gomez, M. L., Gonzalez Hernandez, T., Gonzalez-Alvaro, I, Gonzalez-Montagut Gomez, C., Grandal Delgado, Y., Gratacos Masmitja, J., Hernandez del Rio, A., Instxaurbe, A. R., Irigoyen Oyarzabal, M., V, Jimenez Palop, M., Juan Mas, A., Judez Navarro, E., Larrosa Padro, M., Lopez Longo, F. J., Loza Santamaria, E., Maese Manzano, J., Manero Ruiz, F. J., Mateo Bernardo, I, Mayordomo Gonzalez, L., Mazzucheli, R., Medrano San Idelfonso, M., Naranjo Hernandez, A., Pecondon Espanol, A., Peiro Callizo, E., Quiros Donate, J., Ramos Lopez, P., Rivera Redondo, J., Rodriguez Gomez, M., Rodriguez Lopez, M., Rosello Pardo, R., Sampedro Alvarez, J., Sanmarti Sala, R., Rey Rey, Santos J., Tena Marsa, X., Tenorio Martin, M., Torres Martin, M. C., Urena Garnica, I, Valdazo de Diego, J. P., Valls, M., Villaverde Garcia, V., Zarco Montejo, P., Zubieta Tabernero, J., Balsa, Alejandro, Sanmarti, Raimon, Cabezas, J. A., Cantalejo, M., Chamizo, E., Ciruelo, E., Corrales, A., Cruz, A., Diaz, C., Fiter, J., Freire, M. M., Galindo, M., Garcia de Vicuna, M. R., Gelman, S. M., Gonzalez Crespo, R., Gonzalez Fernandez, C., Gracia, A., Granados, J., Guzman, M. A., Irigoyen, M., V, Juan, A., Juanola, X., Laiz, A., Manero, F. J., Martinez, A., Martinez, F., Mata, C., Maymo, J., Navarro, F. J., Peiro, E., Perez, F., Perez, G., Perez, M., Pujol, M., Quiros, J., Ribas, B., Riera, M., Rivera, J., Rodriguez, J. M., Rosello, R., Tenorio, M., and Toyos, F. J.

Abstract

Objective To evaluate the responsiveness in terms of correlation of the Hospital Universitario La Princesa Index (HUPI) comparatively to the traditional composite indices used to assess disease activity in rheumatoid arthritis (RA), and to compare the performance of HUPI-based response criteria with that of the EULAR response criteria. Methods Secondary data analysis from the following studies: ACT-RAY (clinical trial), PROAR (early RA cohort) and EMECAR (pre-biologic era long term RA cohort). Responsiveness was evaluated by: 1) comparing change from baseline (Delta) of HUPI with Delta in other scores by calculating correlation coefficients; 2) calculating standardised effect sizes. The accuracy of response by HUPI and by EULAR criteria was analyzed using linear regressions in which the dependent variable was change in global assessment by physician (Delta GDA-Phy). Results Delta HUPI correlation with change in all other indices ranged from 0.387 to 0.791); HUPI's standardized effect size was larger than those from the other indices in each database used. In ACT-RAY, depending on visit, between 65 and 80% of patients were equally classified by HUPI and EULAR response criteria. However, HUPI criteria were slightly more stringent, with higher percentage of patients classified as non-responder, especially at early visits. HUPI response criteria showed a slightly higher accuracy than EULAR response criteria when using Delta GDA-Phy as gold standard. Conclusion HUPI shows good responsiveness in terms of correlation in each studied scenario (clinical trial, early RA cohort, and established RA cohort). Response criteria by HUPI seem more stringent than EULAR's.

Published
2019

10. The comparative responsiveness of Hospital Universitario Princesa Index and other composite indices for assessing rheumatoid arthritis activity

Author

Gonzalez-Alvaro, Isidoro, Castrejon, Isabel, Carmona, Loreto, Dougados, M., Huizinga, T., Abu Shakra, M., Alberts, A., Alperi Lopez, M., Amital, H., Aringer, M., Aslanidis, S., Berenbaum, F., Bijlsma, H., Blanco Garcia, F. J., Bliddal, H., Borofsky, M., Brocq, O., Buldakov, S., Cantini, F., Carreno Perez, L., Chahade, W., Ciconelli, R., Codreanu, C., Dahlqvist, S. R., Damjanov, N., Diamantopoulos, A., Dimdina, L., Dimic, A., Dorokhov, A., Dubikov, A., Fadienko, G., Fano, N., Ferreira, G., Gabrielli, A., Gaffney, K., Gaudin, P., Gerlag, D. M., Gerli, R., Goncalves, C. R., Hansen, M. S., Hanvivadhanakul, P., Hoili, C., Hou, A., Hunter, J., Ilic, T., Ionescu, R., Kaine, J., Kakurina, N., Kamalova, R., Kelly, T., Knyazeva, L., Krumina, L., Kurthen, R., Lagrone, R. P., Lapadula, G., Lavrentjevs, V, Lawson, J. G., Lazic, Z., Lejnieks, A., Levy, Y., Lexberg, A., Mader, R., Mariette, X., Markovits, D., Mola, Martin E., Maugars, Y., Guarch, Maymo J., Mazurov, V., I, Mikkelsen, K., Vergles, Morovic J., Nabizadeh, S., Nanagara, R., Nasonov, E. L., Sarabia, Navarro F., Neumann, T., Novak, S., Olech, E., Oza, M., Paran, D., Parsik, E., Pegram, S., Suarez, Pombo M., Popova, T., Puechal, X., Raja, N., Ridley, D., Rosner, I, Rubbert-Roth, A., Rudin, A., Saraux, A., Saulite-Kandevica, D., Settas, L., Sfikakis, P., Sheeran, T., Sizikov, A., Stamenkovic, D., Stefanovic, D., Stolow, J. B., Tan, A. L., Tebib, J., Tishler, M., Tony, H. P., Troum, O. M., Uaratanawong, S., Ucar Angulo, E., Valenzuela, G., van der Laken, K., Van Laar, J., van Riel, P. L. C. M., Vasilopoulos, D., Veldi, T., Vinogradova, I, Vosse, D., Wassenberg, S., Weidmann, C., Weitz, M., Wollenhaupt, J., Xavier, R., Yakupova, S., Zagar, I, Zavgorodnaja, T., Zemerova, E., Zisman, D., Zonova, E., Camona, Loreto, Abasolo Alcazar, L., Alegre de Miguel, C., Andreu Sanchez, J. L., Aragon Diez, A., Balsa Criado, A., Batlle Gualda, E., Belmonte Serrano, M. A., Beltran Audera, J., Beltran Fabregat, J., Bonilla Hernan, G., Caro Fernandez, N., Casado, E., Cebrian Mendez, L., Corteguera Coro, M., Cuadra Diaz, J. L., Cuesta, E., Fiter Areste, J., Freire Gonzalez, M., Galindo Izquierdo, M., Garcia Meijide, J. A., Garcia Gomez, M. C., Gimenez Ubeda, E., Gomez Centeno, E., Gomez Vaquero, C., Gonzalez Fernandez, M. J., Gonzalez Gomez, M. L., Gonzalez Hernandez, T., Gonzalez-Alvaro, I, Gonzalez-Montagut Gomez, C., Grandal Delgado, Y., Gratacos Masmitja, J., Hernandez del Rio, A., Instxaurbe, A. R., Irigoyen Oyarzabal, M., V, Jimenez Palop, M., Juan Mas, A., Judez Navarro, E., Larrosa Padro, M., Lopez Longo, F. J., Loza Santamaria, E., Maese Manzano, J., Manero Ruiz, F. J., Mateo Bernardo, I, Mayordomo Gonzalez, L., Mazzucheli, R., Medrano San Idelfonso, M., Naranjo Hernandez, A., Pecondon Espanol, A., Peiro Callizo, E., Quiros Donate, J., Ramos Lopez, P., Rivera Redondo, J., Rodriguez Gomez, M., Rodriguez Lopez, M., Rosello Pardo, R., Sampedro Alvarez, J., Sanmarti Sala, R., Rey Rey, Santos J., Tena Marsa, X., Tenorio Martin, M., Torres Martin, M. C., Urena Garnica, I, Valdazo de Diego, J. P., Valls, M., Villaverde Garcia, V., Zarco Montejo, P., Zubieta Tabernero, J., Balsa, Alejandro, Sanmarti, Raimon, Cabezas, J. A., Cantalejo, M., Chamizo, E., Ciruelo, E., Corrales, A., Cruz, A., Diaz, C., Fiter, J., Freire, M. M., Galindo, M., Garcia de Vicuna, M. R., Gelman, S. M., Gonzalez Crespo, R., Gonzalez Fernandez, C., Gracia, A., Granados, J., Guzman, M. A., Irigoyen, M., V, Juan, A., Juanola, X., Laiz, A., Manero, F. J., Martinez, A., Martinez, F., Mata, C., Maymo, J., Navarro, F. J., Peiro, E., Perez, F., Perez, G., Perez, M., Pujol, M., Quiros, J., Ribas, B., Riera, M., Rivera, J., Rodriguez, J. M., Rosello, R., Tenorio, M., Toyos, F. J., Gonzalez-Alvaro, Isidoro, Castrejon, Isabel, Carmona, Loreto, Dougados, M., Huizinga, T., Abu Shakra, M., Alberts, A., Alperi Lopez, M., Amital, H., Aringer, M., Aslanidis, S., Berenbaum, F., Bijlsma, H., Blanco Garcia, F. J., Bliddal, H., Borofsky, M., Brocq, O., Buldakov, S., Cantini, F., Carreno Perez, L., Chahade, W., Ciconelli, R., Codreanu, C., Dahlqvist, S. R., Damjanov, N., Diamantopoulos, A., Dimdina, L., Dimic, A., Dorokhov, A., Dubikov, A., Fadienko, G., Fano, N., Ferreira, G., Gabrielli, A., Gaffney, K., Gaudin, P., Gerlag, D. M., Gerli, R., Goncalves, C. R., Hansen, M. S., Hanvivadhanakul, P., Hoili, C., Hou, A., Hunter, J., Ilic, T., Ionescu, R., Kaine, J., Kakurina, N., Kamalova, R., Kelly, T., Knyazeva, L., Krumina, L., Kurthen, R., Lagrone, R. P., Lapadula, G., Lavrentjevs, V, Lawson, J. G., Lazic, Z., Lejnieks, A., Levy, Y., Lexberg, A., Mader, R., Mariette, X., Markovits, D., Mola, Martin E., Maugars, Y., Guarch, Maymo J., Mazurov, V., I, Mikkelsen, K., Vergles, Morovic J., Nabizadeh, S., Nanagara, R., Nasonov, E. L., Sarabia, Navarro F., Neumann, T., Novak, S., Olech, E., Oza, M., Paran, D., Parsik, E., Pegram, S., Suarez, Pombo M., Popova, T., Puechal, X., Raja, N., Ridley, D., Rosner, I, Rubbert-Roth, A., Rudin, A., Saraux, A., Saulite-Kandevica, D., Settas, L., Sfikakis, P., Sheeran, T., Sizikov, A., Stamenkovic, D., Stefanovic, D., Stolow, J. B., Tan, A. L., Tebib, J., Tishler, M., Tony, H. P., Troum, O. M., Uaratanawong, S., Ucar Angulo, E., Valenzuela, G., van der Laken, K., Van Laar, J., van Riel, P. L. C. M., Vasilopoulos, D., Veldi, T., Vinogradova, I, Vosse, D., Wassenberg, S., Weidmann, C., Weitz, M., Wollenhaupt, J., Xavier, R., Yakupova, S., Zagar, I, Zavgorodnaja, T., Zemerova, E., Zisman, D., Zonova, E., Camona, Loreto, Abasolo Alcazar, L., Alegre de Miguel, C., Andreu Sanchez, J. L., Aragon Diez, A., Balsa Criado, A., Batlle Gualda, E., Belmonte Serrano, M. A., Beltran Audera, J., Beltran Fabregat, J., Bonilla Hernan, G., Caro Fernandez, N., Casado, E., Cebrian Mendez, L., Corteguera Coro, M., Cuadra Diaz, J. L., Cuesta, E., Fiter Areste, J., Freire Gonzalez, M., Galindo Izquierdo, M., Garcia Meijide, J. A., Garcia Gomez, M. C., Gimenez Ubeda, E., Gomez Centeno, E., Gomez Vaquero, C., Gonzalez Fernandez, M. J., Gonzalez Gomez, M. L., Gonzalez Hernandez, T., Gonzalez-Alvaro, I, Gonzalez-Montagut Gomez, C., Grandal Delgado, Y., Gratacos Masmitja, J., Hernandez del Rio, A., Instxaurbe, A. R., Irigoyen Oyarzabal, M., V, Jimenez Palop, M., Juan Mas, A., Judez Navarro, E., Larrosa Padro, M., Lopez Longo, F. J., Loza Santamaria, E., Maese Manzano, J., Manero Ruiz, F. J., Mateo Bernardo, I, Mayordomo Gonzalez, L., Mazzucheli, R., Medrano San Idelfonso, M., Naranjo Hernandez, A., Pecondon Espanol, A., Peiro Callizo, E., Quiros Donate, J., Ramos Lopez, P., Rivera Redondo, J., Rodriguez Gomez, M., Rodriguez Lopez, M., Rosello Pardo, R., Sampedro Alvarez, J., Sanmarti Sala, R., Rey Rey, Santos J., Tena Marsa, X., Tenorio Martin, M., Torres Martin, M. C., Urena Garnica, I, Valdazo de Diego, J. P., Valls, M., Villaverde Garcia, V., Zarco Montejo, P., Zubieta Tabernero, J., Balsa, Alejandro, Sanmarti, Raimon, Cabezas, J. A., Cantalejo, M., Chamizo, E., Ciruelo, E., Corrales, A., Cruz, A., Diaz, C., Fiter, J., Freire, M. M., Galindo, M., Garcia de Vicuna, M. R., Gelman, S. M., Gonzalez Crespo, R., Gonzalez Fernandez, C., Gracia, A., Granados, J., Guzman, M. A., Irigoyen, M., V, Juan, A., Juanola, X., Laiz, A., Manero, F. J., Martinez, A., Martinez, F., Mata, C., Maymo, J., Navarro, F. J., Peiro, E., Perez, F., Perez, G., Perez, M., Pujol, M., Quiros, J., Ribas, B., Riera, M., Rivera, J., Rodriguez, J. M., Rosello, R., Tenorio, M., and Toyos, F. J.

Abstract

Objective To evaluate the responsiveness in terms of correlation of the Hospital Universitario La Princesa Index (HUPI) comparatively to the traditional composite indices used to assess disease activity in rheumatoid arthritis (RA), and to compare the performance of HUPI-based response criteria with that of the EULAR response criteria. Methods Secondary data analysis from the following studies: ACT-RAY (clinical trial), PROAR (early RA cohort) and EMECAR (pre-biologic era long term RA cohort). Responsiveness was evaluated by: 1) comparing change from baseline (Delta) of HUPI with Delta in other scores by calculating correlation coefficients; 2) calculating standardised effect sizes. The accuracy of response by HUPI and by EULAR criteria was analyzed using linear regressions in which the dependent variable was change in global assessment by physician (Delta GDA-Phy). Results Delta HUPI correlation with change in all other indices ranged from 0.387 to 0.791); HUPI's standardized effect size was larger than those from the other indices in each database used. In ACT-RAY, depending on visit, between 65 and 80% of patients were equally classified by HUPI and EULAR response criteria. However, HUPI criteria were slightly more stringent, with higher percentage of patients classified as non-responder, especially at early visits. HUPI response criteria showed a slightly higher accuracy than EULAR response criteria when using Delta GDA-Phy as gold standard. Conclusion HUPI shows good responsiveness in terms of correlation in each studied scenario (clinical trial, early RA cohort, and established RA cohort). Response criteria by HUPI seem more stringent than EULAR's.

Published
2019

11. Predicting risk for radiographic damage in rheumatoid arthritis:comparative analysis of the multi-biomarker disease activity score and conventional measures of disease activity in multiple studies

Author

Curtis, Jeffrey R, Brahe, Cecilie H, Østergaard, Mikkel, Lund Hetland, Merete, Hambardzumyan, Karen, Saevarsdottir, Saedis, Wang, Xingbin, Flake Ii, Darl D, Sasso, Eric H, Huizinga, T W, Curtis, Jeffrey R, Brahe, Cecilie H, Østergaard, Mikkel, Lund Hetland, Merete, Hambardzumyan, Karen, Saevarsdottir, Saedis, Wang, Xingbin, Flake Ii, Darl D, Sasso, Eric H, and Huizinga, T W

Abstract

OBJECTIVE: To compare the multi-biomarker disease activity (MBDA) score with the DAS28-CRP and CRP for predicting risk of radiographic progression in patients with rheumatoid arthritis.METHODS: Published studies of the MBDA score and radiographic progression with ≥100 patients per cohort were evaluated. Rates of radiographic progression over 1 year were determined across the low/moderate/high categories for MBDA score (low/moderate/high: <30, 30-44, >44), DAS28-CRP (low/moderate/high: ≤2.67, >2.67-4.09, >4.09) and CRP (low/moderate/high: ≤10, >10-30, >30 mg/L), with positive and negative predictive value (PPV, NPV) and relative risk (RR) determined for high vs. not-high (i.e. low and moderate combined) categories. Patient-level data from studies having all three measures was pooled to: (1) determine a combined RR for radiographic progression in the high vs. not-high categories for each measure; and (2) compare the predictive ability of MBDA score vs. DAS28-CRP by comparing the rates of radiographic progression observed in subgroups created by cross-classifying the high and not-high categories of each measure.RESULTS: Five cohorts were identified for inclusion (total N=929). In each, radiographic progression was more frequent with increasing MBDA scores. Among the three cohorts with requisite data, PPVs were generally similar using categories of MBDA score, DAS28-CRP or CRP but NPVs were greater for MBDA score (93-97%) than DAS28-CRP or CRP (77-87%). RRs for radiographic progression were greater when based on categories of MBDA score than DAS28-CRP or CRP and the combined RR was greater for MBDA score (4.6, p < .0001) than DAS28-CRP (1.7, p = .02) or CRP (1.7, p = .002). For patients cross-classified by MBDA score and DAS28-CRP, high vs. not-high MBDA score significantly predicted radiographic progression independently of DAS28-CRP.CONCLUSIONS: High and not-high MBDA scores were associated with increased and low risk, resp

Published
2019

12. Arthritis prevention in the pre-clinical phase of RA with abatacept (the APIPPRA study): A multi-centre, randomised, double-blind, parallel-group, placebo-controlled clinical trial protocol

Author

Al-Laith, M., Jasenecova, M., Abraham, S., Bosworth, A., Bruce, I. N., Buckley, C. D., Ciurtin, C., D'Agostino, Maria Antonietta, Emery, P., Gaston, H., Isaacs, J. D., Filer, A., Fisher, B. A., Huizinga, T. W. J., Ho, P., Jacklin, C., Lempp, H., Mcinnes, I. B., Pratt, A. G., Ostor, A., Raza, K., Taylor, P. C., Van Schaardenburg, D., Shivapatham, D., Wright, A. J., Vasconcelos, J. C., Kelly, J., Murphy, C., Prevost, A. T., Cope, A. P., D'Agostino M. A. (ORCID:0000-0002-5347-0060), Al-Laith, M., Jasenecova, M., Abraham, S., Bosworth, A., Bruce, I. N., Buckley, C. D., Ciurtin, C., D'Agostino, Maria Antonietta, Emery, P., Gaston, H., Isaacs, J. D., Filer, A., Fisher, B. A., Huizinga, T. W. J., Ho, P., Jacklin, C., Lempp, H., Mcinnes, I. B., Pratt, A. G., Ostor, A., Raza, K., Taylor, P. C., Van Schaardenburg, D., Shivapatham, D., Wright, A. J., Vasconcelos, J. C., Kelly, J., Murphy, C., Prevost, A. T., Cope, A. P., and D'Agostino M. A. (ORCID:0000-0002-5347-0060)

Abstract

Trial design: We present a study protocol for a multi-centre, randomised, double-blind, parallel-group, placebo-controlled trial that seeks to test the feasibility, acceptability and effectiveness of a 52-week period of treatment with the first-in-class co-stimulatory blocker abatacept for preventing or delaying the onset of inflammatory arthritis. Methods: The study aimed to recruit 206 male or female subjects from the secondary care hospital setting across the UK and the Netherlands. Participants who were at least 18 years old, who reported inflammatory sounding joint pain (clinically suspicious arthralgia) and who were found to be positive for serum autoantibodies associated with rheumatoid arthritis (RA) were eligible for enrolment. All study subjects were randomly assigned to receive weekly injections of investigational medicinal product, either abatacept or placebo treatment over the course of a 52-week period. Participants were followed up for a further 52 weeks. The primary endpoint was defined as the time to development of at least three swollen joints or to the fulfilment of the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for RA using swollen but not tender joints, whichever endpoint was met first. In either case, swollen joints were confirmed by ultrasonography. Participants, care givers, and those assessing the outcomes were all blinded to group assignment. Clinical assessors and ultrasonographers were also blinded to each other's assessments for the duration of the study. Conclusions: There is limited experience of the design and implementation of trials for the prevention of inflammatory joint diseases. We discuss the rationale behind choice and duration of treatment and the challenges associated with defining the "at risk" state and offer pragmatic solutions in the protocol to enrolling subjects at risk of RA. Trial registration: Current Controlled Trials, ID: ISRCTN46017566. Registered

Published
2019

13. Predicting risk for radiographic damage in rheumatoid arthritis:comparative analysis of the multi-biomarker disease activity score and conventional measures of disease activity in multiple studies

Author

Curtis, Jeffrey R, Brahe, Cecilie H, Østergaard, Mikkel, Lund Hetland, Merete, Hambardzumyan, Karen, Saevarsdottir, Saedis, Wang, Xingbin, Flake Ii, Darl D, Sasso, Eric H, Huizinga, T W, Curtis, Jeffrey R, Brahe, Cecilie H, Østergaard, Mikkel, Lund Hetland, Merete, Hambardzumyan, Karen, Saevarsdottir, Saedis, Wang, Xingbin, Flake Ii, Darl D, Sasso, Eric H, and Huizinga, T W

Abstract

OBJECTIVE: To compare the multi-biomarker disease activity (MBDA) score with the DAS28-CRP and CRP for predicting risk of radiographic progression in patients with rheumatoid arthritis.METHODS: Published studies of the MBDA score and radiographic progression with ≥100 patients per cohort were evaluated. Rates of radiographic progression over 1 year were determined across the low/moderate/high categories for MBDA score (low/moderate/high: <30, 30-44, >44), DAS28-CRP (low/moderate/high: ≤2.67, >2.67-4.09, >4.09) and CRP (low/moderate/high: ≤10, >10-30, >30 mg/L), with positive and negative predictive value (PPV, NPV) and relative risk (RR) determined for high vs. not-high (i.e. low and moderate combined) categories. Patient-level data from studies having all three measures was pooled to: (1) determine a combined RR for radiographic progression in the high vs. not-high categories for each measure; and (2) compare the predictive ability of MBDA score vs. DAS28-CRP by comparing the rates of radiographic progression observed in subgroups created by cross-classifying the high and not-high categories of each measure.RESULTS: Five cohorts were identified for inclusion (total N=929). In each, radiographic progression was more frequent with increasing MBDA scores. Among the three cohorts with requisite data, PPVs were generally similar using categories of MBDA score, DAS28-CRP or CRP but NPVs were greater for MBDA score (93-97%) than DAS28-CRP or CRP (77-87%). RRs for radiographic progression were greater when based on categories of MBDA score than DAS28-CRP or CRP and the combined RR was greater for MBDA score (4.6, p < .0001) than DAS28-CRP (1.7, p = .02) or CRP (1.7, p = .002). For patients cross-classified by MBDA score and DAS28-CRP, high vs. not-high MBDA score significantly predicted radiographic progression independently of DAS28-CRP.CONCLUSIONS: High and not-high MBDA scores were associated with increased and low risk, resp

Published
2019

15. Fine-Mapping Identifies Causal Variants for RA and T1D in DNASE1L3, Sirpg, MEG3, TNFAIP3 and CD28/CTLA4 Loc

Author

Westra, Harm-Jan, Martinez-Bonet, Marta, Onengut, Suna, Lee, Annette, Luo, Yang, Teslovich, Nikola, Worthington, Jane, Martin, Javier, Huizinga, T. W. J., Klareskog, Lars, Rantapää Dahlqvist, Solbritt, Chen, Wei-Min, Quinlan, Aaron, Todd, John, Eyre, Stephen, Nigrovic, Peter, Gregersen, Peter, Rich, Stephen, Raychaudhuri, Soumya, Westra, Harm-Jan, Martinez-Bonet, Marta, Onengut, Suna, Lee, Annette, Luo, Yang, Teslovich, Nikola, Worthington, Jane, Martin, Javier, Huizinga, T. W. J., Klareskog, Lars, Rantapää Dahlqvist, Solbritt, Chen, Wei-Min, Quinlan, Aaron, Todd, John, Eyre, Stephen, Nigrovic, Peter, Gregersen, Peter, Rich, Stephen, and Raychaudhuri, Soumya

Abstract

Supplement: 10Meeting Abstract: 2826

Published
2017

16. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update

Author

Smolen, J.S., Landewe, R., Bijlsma, J., Burmester, G., Chatzidionysiou, K., Dougados, M., Nam, J., Ramiro, S., Voshaar, M., Vollenhoven, R. van, Aletaha, D., Aringer, M., Boers, M, Buckley, C.D., Buttgereit, F., Bykerk, V., Cardiel, M., Combe, B., Cutolo, M., Eijk-Hustings, Y. van, Emery, P., Finckh, A., Gabay, C., Gomez-Reino, J., Gossec, L., Gottenberg, J.-E., Hazes, J.M., Huizinga, T., Jani, M., Karateev, D., Kouloumas, M., Kvien, T., Li, Z., Mariette, X., McInnes, I., Mysler, E., Nash, P., Pavelka, K., Poor, G., Richez, C., Riel, P. van, Rubbert-Roth, A., Saag, K., Silva, J., Stamm, T., Takeuchi, T., Westhovens, R., Wit, M. de, Heijde, D. van der, Smolen, J.S., Landewe, R., Bijlsma, J., Burmester, G., Chatzidionysiou, K., Dougados, M., Nam, J., Ramiro, S., Voshaar, M., Vollenhoven, R. van, Aletaha, D., Aringer, M., Boers, M, Buckley, C.D., Buttgereit, F., Bykerk, V., Cardiel, M., Combe, B., Cutolo, M., Eijk-Hustings, Y. van, Emery, P., Finckh, A., Gabay, C., Gomez-Reino, J., Gossec, L., Gottenberg, J.-E., Hazes, J.M., Huizinga, T., Jani, M., Karateev, D., Kouloumas, M., Kvien, T., Li, Z., Mariette, X., McInnes, I., Mysler, E., Nash, P., Pavelka, K., Poor, G., Richez, C., Riel, P. van, Rubbert-Roth, A., Saag, K., Silva, J., Stamm, T., Takeuchi, T., Westhovens, R., Wit, M. de, and Heijde, D. van der

Abstract

Contains fulltext : 177336.pdf (publisher's version ) (Closed access)

Published
2017

17. Presence of anticitrullinated protein antibodies in a large population-based cohort from the Netherlands

Author

van Zanten, A, Arends, S, Roozendaal, C, Limburg, P C, Maas, F, Trouw, L A, Toes, R E M, Huizinga, T W J, Bootsma, H, Brouwer, E, van Zanten, A, Arends, S, Roozendaal, C, Limburg, P C, Maas, F, Trouw, L A, Toes, R E M, Huizinga, T W J, Bootsma, H, and Brouwer, E

Abstract

Objectives To determine the prevalence of anticitrullinated protein antibodies (ACPAs) and their association with known rheumatoid arthritis (RA) risk factors in the general population.Methods Lifelines is a multidisciplinary prospective population-based cohort study in the Netherlands. Cross-sectional data from 40 136 participants were used. The detection of ACPA was performed by measuring anti-CCP2 on the Phadia-250 analyser with levels >= 6.2 U/mL considered positive. An extensive questionnaire was taken on demographic and clinical information, including smoking, periodontal health and early symptoms of musculoskeletal disorders. RA was defined by a combination of self-reported RA, medication use for the indication of rheumatism and visiting a medical specialist within the last year.Results Of the total 40 136 unselected individuals, 401 (1.0%) had ACPA level >= 6.2 U/mL. ACPA positivity was significantly associated with older age, female gender, smoking, joint complaints, RA and first degree relatives with rheumatism. Of the ACPA-positive participants, 22.4% had RA (15.2% had defined RA according to our criteria and 7.2% self-reported RA only). In participants without RA, 311 (0.8%) were ACPA-positive. In the non-RA group, older age, smoking and joint complaints remained significantly more frequently present in ACPA-positive compared with ACPA-negative participants.Conclusions In this large population-based study, the prevalence of ACPA levels >= 6.2 U/mL was 1.0% for the total group and 0.8% when excluding patients with RA. Older age, smoking and joint complaints were more frequently present in ACPA-positive Lifelines participants. To our knowledge, this study is the largest study to date on ACPA positivity in the general, mostly Caucasian population.

Published
2017

18. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update

Author

Smolen, J.S., Landewe, R., Bijlsma, J., Burmester, G., Chatzidionysiou, K., Dougados, M., Nam, J., Ramiro, S., Voshaar, M., Vollenhoven, R. van, Aletaha, D., Aringer, M., Boers, M, Buckley, C.D., Buttgereit, F., Bykerk, V., Cardiel, M., Combe, B., Cutolo, M., Eijk-Hustings, Y. van, Emery, P., Finckh, A., Gabay, C., Gomez-Reino, J., Gossec, L., Gottenberg, J.-E., Hazes, J.M., Huizinga, T., Jani, M., Karateev, D., Kouloumas, M., Kvien, T., Li, Z., Mariette, X., McInnes, I., Mysler, E., Nash, P., Pavelka, K., Poor, G., Richez, C., Riel, P. van, Rubbert-Roth, A., Saag, K., Silva, J., Stamm, T., Takeuchi, T., Westhovens, R., Wit, M. de, Heijde, D. van der, Smolen, J.S., Landewe, R., Bijlsma, J., Burmester, G., Chatzidionysiou, K., Dougados, M., Nam, J., Ramiro, S., Voshaar, M., Vollenhoven, R. van, Aletaha, D., Aringer, M., Boers, M, Buckley, C.D., Buttgereit, F., Bykerk, V., Cardiel, M., Combe, B., Cutolo, M., Eijk-Hustings, Y. van, Emery, P., Finckh, A., Gabay, C., Gomez-Reino, J., Gossec, L., Gottenberg, J.-E., Hazes, J.M., Huizinga, T., Jani, M., Karateev, D., Kouloumas, M., Kvien, T., Li, Z., Mariette, X., McInnes, I., Mysler, E., Nash, P., Pavelka, K., Poor, G., Richez, C., Riel, P. van, Rubbert-Roth, A., Saag, K., Silva, J., Stamm, T., Takeuchi, T., Westhovens, R., Wit, M. de, and Heijde, D. van der

Abstract

Contains fulltext : 177336.pdf (publisher's version ) (Closed access)

Published
2017

19. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update

Author

Smolen, J.S., Landewe, R., Bijlsma, J., Burmester, G., Chatzidionysiou, K., Dougados, M., Nam, J., Ramiro, S., Voshaar, M., Vollenhoven, R. van, Aletaha, D., Aringer, M., Boers, M, Buckley, C.D., Buttgereit, F., Bykerk, V., Cardiel, M., Combe, B., Cutolo, M., Eijk-Hustings, Y. van, Emery, P., Finckh, A., Gabay, C., Gomez-Reino, J., Gossec, L., Gottenberg, J.-E., Hazes, J.M., Huizinga, T., Jani, M., Karateev, D., Kouloumas, M., Kvien, T., Li, Z., Mariette, X., McInnes, I., Mysler, E., Nash, P., Pavelka, K., Poor, G., Richez, C., Riel, P. van, Rubbert-Roth, A., Saag, K., Silva, J., Stamm, T., Takeuchi, T., Westhovens, R., Wit, M. de, Heijde, D. van der, Smolen, J.S., Landewe, R., Bijlsma, J., Burmester, G., Chatzidionysiou, K., Dougados, M., Nam, J., Ramiro, S., Voshaar, M., Vollenhoven, R. van, Aletaha, D., Aringer, M., Boers, M, Buckley, C.D., Buttgereit, F., Bykerk, V., Cardiel, M., Combe, B., Cutolo, M., Eijk-Hustings, Y. van, Emery, P., Finckh, A., Gabay, C., Gomez-Reino, J., Gossec, L., Gottenberg, J.-E., Hazes, J.M., Huizinga, T., Jani, M., Karateev, D., Kouloumas, M., Kvien, T., Li, Z., Mariette, X., McInnes, I., Mysler, E., Nash, P., Pavelka, K., Poor, G., Richez, C., Riel, P. van, Rubbert-Roth, A., Saag, K., Silva, J., Stamm, T., Takeuchi, T., Westhovens, R., Wit, M. de, and Heijde, D. van der

Abstract

Contains fulltext : 177336.pdf (publisher's version ) (Closed access)

Published
2017

21. Impact of commercial strain use on saccharomyces cerevisiae population structure and dynamics in pinot noir vineyards and spontaneous fermentations of a canadian Winery

Author

Rydén Aulin, M, Boumpas, D, Bultink, I, Callejas, Rubio JL, Caminal Montero, L, Castro, A, Colodro Ruiz, A, Doria, A, Dörner, T, Gonzalez Echavarri, C, Gremese, Elisa, Houssiau, Fa, Huizinga, T, Inanç, M, Isenberg, D, Iuliano, A, Jacobsen, S, Jimenéz Alonso, J, Kovács, L, Mariette, X, Mosca, M, Nived, O, Oristrell, J, Ramos Casals, M, Rascón, J, Ruiz Irastorza, G, Sáez Comet, L, Salvador Cervelló, G, Sebastiani, Gd, Squatrito, D, Szücs, G, Voskuyl, A, Van Vollenhoven, R., Gremese, Elisa (ORCID:0000-0002-2248-1058), Rydén Aulin, M, Boumpas, D, Bultink, I, Callejas, Rubio JL, Caminal Montero, L, Castro, A, Colodro Ruiz, A, Doria, A, Dörner, T, Gonzalez Echavarri, C, Gremese, Elisa, Houssiau, Fa, Huizinga, T, Inanç, M, Isenberg, D, Iuliano, A, Jacobsen, S, Jimenéz Alonso, J, Kovács, L, Mariette, X, Mosca, M, Nived, O, Oristrell, J, Ramos Casals, M, Rascón, J, Ruiz Irastorza, G, Sáez Comet, L, Salvador Cervelló, G, Sebastiani, Gd, Squatrito, D, Szücs, G, Voskuyl, A, Van Vollenhoven, R., and Gremese, Elisa (ORCID:0000-0002-2248-1058)

Abstract

Wine is produced by one of two methods: inoculated fermentation, where a commerciallyproduced, single Saccharomyces cerevisiae (S. cerevisiae) yeast strain is used; or the traditional spontaneous fermentation, where yeast present on grape and winery surfaces carry out the fermentative process. Spontaneous fermentations are characterized by a diverse succession of yeast, ending with one or multiple strains of S. cerevisiae dominating the fermentation. In wineries using both fermentation methods, commercial strains may dominate spontaneous fermentations. We elucidate the impact of the winery environment and commercial strain use on S. cerevisiae population structure in spontaneous fermentations over two vintages by comparing S. cerevisiae populations in aseptically fermented grapes from a Canadian Pinot Noir vineyard to S. cerevisiae populations in winery-conducted fermentations of grapes from the same vineyard. We also characterize the vineyard-associated S. cerevisiae populations in two other geographically separate Pinot Noir vineyards farmed by the same winery. Winery fermentations were not dominated by commercial strains, but by a diverse number of strains with genotypes similar to commercial strains, suggesting that a population of S. cerevisiae derived from commercial strains is resident in the winery. Commercial and commercial-related yeast were also identified in the three vineyards examined, although at a lower frequency. There is low genetic differentiation and S. cerevisiae population structure between vineyards and between the vineyard and winery that persisted over both vintages, indicating commercial yeast are a driver of S. cerevisiae population structure. We also have evidence of distinct and persistent populations of winery and vineyard-associated S. cerevisiae populations unrelated to commercial strains. This study is the first to characterize S. cerevisiae populations in Canadian vineyards.

Published
2016

23. Association of valine and leucine at HLA-DRB1 position 11 with radiographic progression in rheumatoid arthritis, independent of the shared epitope alleles but not independent of anti-citrullinated protein antibodies

Author

van Steenbergen, H. W., Raychaudhuri, S., Rodríguez-Rodríguez, L., Rantapää-Dahlqvist, Solbritt, Berglin, Ewa, Toes, R. E. M., Huizinga, T. W. J., Fernández-Gutiérrez, B., Gregersen, P. K., van der Helm-van Mil, A. H. M., van Steenbergen, H. W., Raychaudhuri, S., Rodríguez-Rodríguez, L., Rantapää-Dahlqvist, Solbritt, Berglin, Ewa, Toes, R. E. M., Huizinga, T. W. J., Fernández-Gutiérrez, B., Gregersen, P. K., and van der Helm-van Mil, A. H. M.

Abstract

OBJECTIVE: For decades it has been known that the HLA-DRB1 shared epitope (SE) alleles are associated with an increased risk of development and progression of rheumatoid arthritis (RA). Recently, the following variations in the peptide-binding grooves of HLA molecules that predispose to RA development have been identified: Val and Leu at HLA-DRB1 position 11, Asp at HLA-B position 9, and Phe at HLA-DPB1 position 9. This study was undertaken to investigate whether these variants are also associated with radiographic progression in RA, independent of SE and anti-citrullinated protein antibody (ACPA) status. METHODS: A total of 4,911 radiograph sets from 1,878 RA patients included in the Leiden Early Arthritis Clinic (The Netherlands), Umeå (Sweden), Hospital Clinico San Carlos-Rheumatoid Arthritis (Spain), and National Data Bank for Rheumatic Diseases (US) cohorts were studied. HLA was imputed using single-nucleotide polymorphism data from an Immunochip, and the amino acids listed above were tested in relation to radiographic progression per cohort using an additive model. Results from the 4 cohorts were combined in inverse-variance weighted meta-analyses using a fixed-effects model. Analyses were conditioned on SE and ACPA status. RESULTS: Val and Leu at HLA-DRB1 position 11 were associated with more radiographic progression (meta-analysis P = 5.11 × 10(-7)); this effect was independent of SE status (meta-analysis P = 0.022) but not independent of ACPA status. Phe at HLA-DPB1 position 9 was associated with more severe radiographic progression (meta-analysis P = 0.024), though not independent of SE status. Asp at HLA-B position 9 was not associated with radiographic progression. CONCLUSION: Val and Leu at HLA-DRB1 position 11 conferred a risk of a higher rate of radiographic progression independent of SE status but not independent of ACPA status. These findings support the relevance of these amino acids at position 11.

Published
2015
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24. A genome-wide association study of rheumatoid arthritis without antibodies against citrullinated peptides

Author

Bossini-Castillo, L., Kovel, C.G.F. de, Kallberg, H., Slot, R. van 't, Italiaander, A., Coenen, M.J., Tak, P.P., Posthumus, M.D., Wijmenga, C., Huizinga, T., Helm-van Mil, A.H. van der, Stoeken-Rijsbergen, G., Rodriguez-Rodriguez, L., Balsa, A., Gonzalez-Alvaro, I., Gonzalez-Gay, M.A., Gomez-Vaquero, C., Franke, B., Vermeulen, H.H., Horst-Bruinsma, I.E., Dijkmans, B.A., Wolbink, G.J., Ophoff, R.A., Maehlen, M.T., Riel, P. van, Merriman, M., Klareskog, L., Lie, B.A., Merriman, T., Crusius, J.B.A., Brouwer, E., Martin, J., Vries, N. de, Toes, R., Padyukov, L., Koeleman, B.P.C., Bossini-Castillo, L., Kovel, C.G.F. de, Kallberg, H., Slot, R. van 't, Italiaander, A., Coenen, M.J., Tak, P.P., Posthumus, M.D., Wijmenga, C., Huizinga, T., Helm-van Mil, A.H. van der, Stoeken-Rijsbergen, G., Rodriguez-Rodriguez, L., Balsa, A., Gonzalez-Alvaro, I., Gonzalez-Gay, M.A., Gomez-Vaquero, C., Franke, B., Vermeulen, H.H., Horst-Bruinsma, I.E., Dijkmans, B.A., Wolbink, G.J., Ophoff, R.A., Maehlen, M.T., Riel, P. van, Merriman, M., Klareskog, L., Lie, B.A., Merriman, T., Crusius, J.B.A., Brouwer, E., Martin, J., Vries, N. de, Toes, R., Padyukov, L., and Koeleman, B.P.C.

Abstract

Contains fulltext : 155045.pdf (publisher's version ) (Closed access), Introduction Rheumatoid arthritis (RA) patients can be classified based on presence or absence of anticitrullinated peptide antibodies (ACPA) in their serum. This heterogeneity among patients may reflect important biological differences underlying the disease process. To date, the majority of genetic studies have focused on the ACPA-positive group. Therefore, our goal was to analyse the genetic risk factors that contribute to ACPA-negative RA. Methods We performed a large-scale genome-wide association study (GWAS) in three Caucasian European cohorts comprising 1148 ACPA-negative RA patients and 6008 controls. All patients were screened using the Illumina Human Cyto-12 chip, and controls were genotyped using different genome-wide platforms. Population-independent analyses were carried out by means of logistic regression. Meta-analysis with previously published data was performed as follow-up for selected signals (reaching a total of 1922 ACPA-negative RA patients and 7087 controls). Imputation of classical HLA alleles, amino acid residues and single nucleotide polymorphisms was undertaken. Results The combined analysis of the studied cohorts resulted in identification of a peak of association in the HLA-region and several suggestive non-HLA associations. Meta-analysis with previous reports confirmed the association of the HLA region with this subset and an observed association in the CLYBL locus remained suggestive. The imputation and deep interrogation of the HLA region led to identification of a two amino acid model (HLA-B at position 9 and HLA-DRB1 at position 11) that accounted for the observed genome-wide associations in this region. Conclusions Our study shed light on the influence of the HLA region in ACPA-negative RA and identified a suggestive risk locus for this condition.

Published
2015

26. A genome-wide association study of rheumatoid arthritis without antibodies against citrullinated peptides

Author

Bossini-Castillo, L., de Kovel, C., Kallberg, H., van 't Slot, R., Italiaander, A., Coenen, M., Tak, P. P., Posthumus, M. D., Wijmenga, C., Huizinga, T., van der Helm-van Mil, A. H. M., Stoeken-Rijsbergen, G., Rodriguez-Rodriguez, Luis, Balsa, Alejandro, Gonzalez-Alvaro, Isidoro, Angel Gonzalez-Gay, Miguel, Gomez-Vaquero, Carmen, Franke, B., Vermeulen, S., van der Horst-Bruinsma, I. E., Dijkmans, B. A. C., Wolbink, G. J., Ophoff, R. A., Maehlen, M. T., van Riel, P., Merriman, M., Klareskog, L., Lie, B. A., Merriman, T., Crusius, J. B. A., Brouwer, E., Martin, J., de Vries, N., Toes, R., Padyukov, L., Koeleman, B. P. C., LifeLines Cohort Study, Bossini-Castillo, L., de Kovel, C., Kallberg, H., van 't Slot, R., Italiaander, A., Coenen, M., Tak, P. P., Posthumus, M. D., Wijmenga, C., Huizinga, T., van der Helm-van Mil, A. H. M., Stoeken-Rijsbergen, G., Rodriguez-Rodriguez, Luis, Balsa, Alejandro, Gonzalez-Alvaro, Isidoro, Angel Gonzalez-Gay, Miguel, Gomez-Vaquero, Carmen, Franke, B., Vermeulen, S., van der Horst-Bruinsma, I. E., Dijkmans, B. A. C., Wolbink, G. J., Ophoff, R. A., Maehlen, M. T., van Riel, P., Merriman, M., Klareskog, L., Lie, B. A., Merriman, T., Crusius, J. B. A., Brouwer, E., Martin, J., de Vries, N., Toes, R., Padyukov, L., Koeleman, B. P. C., and LifeLines Cohort Study

Published
2015

28. A genome-wide association study of rheumatoid arthritis without antibodies against citrullinated peptides

Author

Bossini-Castillo, L., de Kovel, C., Kallberg, H., van 't Slot, R., Italiaander, A., Coenen, M., Tak, P. P., Posthumus, M. D., Wijmenga, C., Huizinga, T., van der Helm-van Mil, A. H. M., Stoeken-Rijsbergen, G., Rodriguez-Rodriguez, Luis, Balsa, Alejandro, Gonzalez-Alvaro, Isidoro, Angel Gonzalez-Gay, Miguel, Gomez-Vaquero, Carmen, Franke, B., Vermeulen, S., van der Horst-Bruinsma, I. E., Dijkmans, B. A. C., Wolbink, G. J., Ophoff, R. A., Maehlen, M. T., van Riel, P., Merriman, M., Klareskog, L., Lie, B. A., Merriman, T., Crusius, J. B. A., Brouwer, E., Martin, J., de Vries, N., Toes, R., Padyukov, L., Koeleman, B. P. C., LifeLines Cohort Study, Bossini-Castillo, L., de Kovel, C., Kallberg, H., van 't Slot, R., Italiaander, A., Coenen, M., Tak, P. P., Posthumus, M. D., Wijmenga, C., Huizinga, T., van der Helm-van Mil, A. H. M., Stoeken-Rijsbergen, G., Rodriguez-Rodriguez, Luis, Balsa, Alejandro, Gonzalez-Alvaro, Isidoro, Angel Gonzalez-Gay, Miguel, Gomez-Vaquero, Carmen, Franke, B., Vermeulen, S., van der Horst-Bruinsma, I. E., Dijkmans, B. A. C., Wolbink, G. J., Ophoff, R. A., Maehlen, M. T., van Riel, P., Merriman, M., Klareskog, L., Lie, B. A., Merriman, T., Crusius, J. B. A., Brouwer, E., Martin, J., de Vries, N., Toes, R., Padyukov, L., Koeleman, B. P. C., and LifeLines Cohort Study

Published
2015

29. A genome-wide association study of rheumatoid arthritis without antibodies against citrullinated peptides

Author

Bossini-Castillo, L., Kovel, C.G.F. de, Kallberg, H., Slot, R. van 't, Italiaander, A., Coenen, M.J., Tak, P.P., Posthumus, M.D., Wijmenga, C., Huizinga, T., Helm-van Mil, A.H. van der, Stoeken-Rijsbergen, G., Rodriguez-Rodriguez, L., Balsa, A., Gonzalez-Alvaro, I., Gonzalez-Gay, M.A., Gomez-Vaquero, C., Franke, B., Vermeulen, H.H., Horst-Bruinsma, I.E. van der, Dijkmans, B.A., Wolbink, G.J., Ophoff, R.A., Maehlen, M.T., Riel, P. van, Merriman, M., Klareskog, L., Lie, B.A., Merriman, T., Crusius, J.B.A., Brouwer, E., Martin, J., Vries, N. de, Toes, R., Padyukov, L., Koeleman, B.P.C., Bossini-Castillo, L., Kovel, C.G.F. de, Kallberg, H., Slot, R. van 't, Italiaander, A., Coenen, M.J., Tak, P.P., Posthumus, M.D., Wijmenga, C., Huizinga, T., Helm-van Mil, A.H. van der, Stoeken-Rijsbergen, G., Rodriguez-Rodriguez, L., Balsa, A., Gonzalez-Alvaro, I., Gonzalez-Gay, M.A., Gomez-Vaquero, C., Franke, B., Vermeulen, H.H., Horst-Bruinsma, I.E. van der, Dijkmans, B.A., Wolbink, G.J., Ophoff, R.A., Maehlen, M.T., Riel, P. van, Merriman, M., Klareskog, L., Lie, B.A., Merriman, T., Crusius, J.B.A., Brouwer, E., Martin, J., Vries, N. de, Toes, R., Padyukov, L., and Koeleman, B.P.C.

Abstract

Contains fulltext : 155045.pdf (publisher's version ) (Closed access), Introduction Rheumatoid arthritis (RA) patients can be classified based on presence or absence of anticitrullinated peptide antibodies (ACPA) in their serum. This heterogeneity among patients may reflect important biological differences underlying the disease process. To date, the majority of genetic studies have focused on the ACPA-positive group. Therefore, our goal was to analyse the genetic risk factors that contribute to ACPA-negative RA. Methods We performed a large-scale genome-wide association study (GWAS) in three Caucasian European cohorts comprising 1148 ACPA-negative RA patients and 6008 controls. All patients were screened using the Illumina Human Cyto-12 chip, and controls were genotyped using different genome-wide platforms. Population-independent analyses were carried out by means of logistic regression. Meta-analysis with previously published data was performed as follow-up for selected signals (reaching a total of 1922 ACPA-negative RA patients and 7087 controls). Imputation of classical HLA alleles, amino acid residues and single nucleotide polymorphisms was undertaken. Results The combined analysis of the studied cohorts resulted in identification of a peak of association in the HLA-region and several suggestive non-HLA associations. Meta-analysis with previous reports confirmed the association of the HLA region with this subset and an observed association in the CLYBL locus remained suggestive. The imputation and deep interrogation of the HLA region led to identification of a two amino acid model (HLA-B at position 9 and HLA-DRB1 at position 11) that accounted for the observed genome-wide associations in this region. Conclusions Our study shed light on the influence of the HLA region in ACPA-negative RA and identified a suggestive risk locus for this condition.

Published
2015

31. A genome-wide association study of rheumatoid arthritis without antibodies against citrullinated peptides

Author

Bossini-Castillo, L., de Kovel, C., Kallberg, H., van 't Slot, R., Italiaander, A., Coenen, M., Tak, P. P., Posthumus, M. D., Wijmenga, C., Huizinga, T., van der Helm-van Mil, A. H. M., Stoeken-Rijsbergen, G., Rodriguez-Rodriguez, Luis, Balsa, Alejandro, Gonzalez-Alvaro, Isidoro, Angel Gonzalez-Gay, Miguel, Gomez-Vaquero, Carmen, Franke, B., Vermeulen, S., van der Horst-Bruinsma, I. E., Dijkmans, B. A. C., Wolbink, G. J., Ophoff, R. A., Maehlen, M. T., van Riel, P., Merriman, M., Klareskog, L., Lie, B. A., Merriman, T., Crusius, J. B. A., Brouwer, E., Martin, J., de Vries, N., Toes, R., Padyukov, L., Koeleman, B. P. C., LifeLines Cohort Study, Bossini-Castillo, L., de Kovel, C., Kallberg, H., van 't Slot, R., Italiaander, A., Coenen, M., Tak, P. P., Posthumus, M. D., Wijmenga, C., Huizinga, T., van der Helm-van Mil, A. H. M., Stoeken-Rijsbergen, G., Rodriguez-Rodriguez, Luis, Balsa, Alejandro, Gonzalez-Alvaro, Isidoro, Angel Gonzalez-Gay, Miguel, Gomez-Vaquero, Carmen, Franke, B., Vermeulen, S., van der Horst-Bruinsma, I. E., Dijkmans, B. A. C., Wolbink, G. J., Ophoff, R. A., Maehlen, M. T., van Riel, P., Merriman, M., Klareskog, L., Lie, B. A., Merriman, T., Crusius, J. B. A., Brouwer, E., Martin, J., de Vries, N., Toes, R., Padyukov, L., Koeleman, B. P. C., and LifeLines Cohort Study

Published
2015

32. A genome-wide association study of rheumatoid arthritis without antibodies against citrullinated peptides

Author

Bossini-Castillo, L., Kovel, C.G.F. de, Kallberg, H., Slot, R. van 't, Italiaander, A., Coenen, M.J., Tak, P.P., Posthumus, M.D., Wijmenga, C., Huizinga, T., Helm-van Mil, A.H. van der, Stoeken-Rijsbergen, G., Rodriguez-Rodriguez, L., Balsa, A., Gonzalez-Alvaro, I., Gonzalez-Gay, M.A., Gomez-Vaquero, C., Franke, B., Vermeulen, H.H., Horst-Bruinsma, I.E. van der, Dijkmans, B.A., Wolbink, G.J., Ophoff, R.A., Maehlen, M.T., Riel, P. van, Merriman, M., Klareskog, L., Lie, B.A., Merriman, T., Crusius, J.B.A., Brouwer, E., Martin, J., Vries, N. de, Toes, R., Padyukov, L., Koeleman, B.P.C., Bossini-Castillo, L., Kovel, C.G.F. de, Kallberg, H., Slot, R. van 't, Italiaander, A., Coenen, M.J., Tak, P.P., Posthumus, M.D., Wijmenga, C., Huizinga, T., Helm-van Mil, A.H. van der, Stoeken-Rijsbergen, G., Rodriguez-Rodriguez, L., Balsa, A., Gonzalez-Alvaro, I., Gonzalez-Gay, M.A., Gomez-Vaquero, C., Franke, B., Vermeulen, H.H., Horst-Bruinsma, I.E. van der, Dijkmans, B.A., Wolbink, G.J., Ophoff, R.A., Maehlen, M.T., Riel, P. van, Merriman, M., Klareskog, L., Lie, B.A., Merriman, T., Crusius, J.B.A., Brouwer, E., Martin, J., Vries, N. de, Toes, R., Padyukov, L., and Koeleman, B.P.C.

Abstract

Contains fulltext : 155045.pdf (publisher's version ) (Closed access), Introduction Rheumatoid arthritis (RA) patients can be classified based on presence or absence of anticitrullinated peptide antibodies (ACPA) in their serum. This heterogeneity among patients may reflect important biological differences underlying the disease process. To date, the majority of genetic studies have focused on the ACPA-positive group. Therefore, our goal was to analyse the genetic risk factors that contribute to ACPA-negative RA. Methods We performed a large-scale genome-wide association study (GWAS) in three Caucasian European cohorts comprising 1148 ACPA-negative RA patients and 6008 controls. All patients were screened using the Illumina Human Cyto-12 chip, and controls were genotyped using different genome-wide platforms. Population-independent analyses were carried out by means of logistic regression. Meta-analysis with previously published data was performed as follow-up for selected signals (reaching a total of 1922 ACPA-negative RA patients and 7087 controls). Imputation of classical HLA alleles, amino acid residues and single nucleotide polymorphisms was undertaken. Results The combined analysis of the studied cohorts resulted in identification of a peak of association in the HLA-region and several suggestive non-HLA associations. Meta-analysis with previous reports confirmed the association of the HLA region with this subset and an observed association in the CLYBL locus remained suggestive. The imputation and deep interrogation of the HLA region led to identification of a two amino acid model (HLA-B at position 9 and HLA-DRB1 at position 11) that accounted for the observed genome-wide associations in this region. Conclusions Our study shed light on the influence of the HLA region in ACPA-negative RA and identified a suggestive risk locus for this condition.

Published
2015

42. A genome-wide association study of rheumatoid arthritis without antibodies against citrullinated peptides

Author

Bossini-Castillo, L., Kovel, C.G.F. de, Kallberg, H., Slot, R. van 't, Italiaander, A., Coenen, M.J., Tak, P.P., Posthumus, M.D., Wijmenga, C., Huizinga, T., Helm-van Mil, A.H. van der, Stoeken-Rijsbergen, G., Rodriguez-Rodriguez, L., Balsa, A., Gonzalez-Alvaro, I., Gonzalez-Gay, M.A., Gomez-Vaquero, C., Franke, B., Vermeulen, H.H., Horst-Bruinsma, I.E. van der, Dijkmans, B.A., Wolbink, G.J., Ophoff, R.A., Maehlen, M.T., Riel, P. van, Merriman, M., Klareskog, L., Lie, B.A., Merriman, T., Crusius, J.B.A., Brouwer, E., Martin, J., Vries, N. de, Toes, R., Padyukov, L., Koeleman, B.P.C., Bossini-Castillo, L., Kovel, C.G.F. de, Kallberg, H., Slot, R. van 't, Italiaander, A., Coenen, M.J., Tak, P.P., Posthumus, M.D., Wijmenga, C., Huizinga, T., Helm-van Mil, A.H. van der, Stoeken-Rijsbergen, G., Rodriguez-Rodriguez, L., Balsa, A., Gonzalez-Alvaro, I., Gonzalez-Gay, M.A., Gomez-Vaquero, C., Franke, B., Vermeulen, H.H., Horst-Bruinsma, I.E. van der, Dijkmans, B.A., Wolbink, G.J., Ophoff, R.A., Maehlen, M.T., Riel, P. van, Merriman, M., Klareskog, L., Lie, B.A., Merriman, T., Crusius, J.B.A., Brouwer, E., Martin, J., Vries, N. de, Toes, R., Padyukov, L., and Koeleman, B.P.C.

Abstract

Contains fulltext : 155045.pdf (Publisher’s version ) (Closed access), Introduction Rheumatoid arthritis (RA) patients can be classified based on presence or absence of anticitrullinated peptide antibodies (ACPA) in their serum. This heterogeneity among patients may reflect important biological differences underlying the disease process. To date, the majority of genetic studies have focused on the ACPA-positive group. Therefore, our goal was to analyse the genetic risk factors that contribute to ACPA-negative RA. Methods We performed a large-scale genome-wide association study (GWAS) in three Caucasian European cohorts comprising 1148 ACPA-negative RA patients and 6008 controls. All patients were screened using the Illumina Human Cyto-12 chip, and controls were genotyped using different genome-wide platforms. Population-independent analyses were carried out by means of logistic regression. Meta-analysis with previously published data was performed as follow-up for selected signals (reaching a total of 1922 ACPA-negative RA patients and 7087 controls). Imputation of classical HLA alleles, amino acid residues and single nucleotide polymorphisms was undertaken. Results The combined analysis of the studied cohorts resulted in identification of a peak of association in the HLA-region and several suggestive non-HLA associations. Meta-analysis with previous reports confirmed the association of the HLA region with this subset and an observed association in the CLYBL locus remained suggestive. The imputation and deep interrogation of the HLA region led to identification of a two amino acid model (HLA-B at position 9 and HLA-DRB1 at position 11) that accounted for the observed genome-wide associations in this region. Conclusions Our study shed light on the influence of the HLA region in ACPA-negative RA and identified a suggestive risk locus for this condition.

Published
2015

44. A genome-wide association study of rheumatoid arthritis without antibodies against citrullinated peptides

Author

Genetica Groep Koeleman, Hersenen-Bedrijfsvoering, MMB, Child Health, Bossini-Castillo, L., de Kovel, C., Kallberg, H., van 't Slot, R., Italiaander, A., Coenen, M., Tak, P. P., Posthumus, M. D., Wijmenga, C., Huizinga, T., van der Helm-van Mil, A. H. M., Stoeken-Rijsbergen, G., Rodriguez-Rodriguez, Luis, Balsa, Alejandro, Gonzalez-Alvaro, Isidoro, Angel Gonzalez-Gay, Miguel, Gomez-Vaquero, Carmen, Franke, B., Vermeulen, S., van der Horst-Bruinsma, I. E., Dijkmans, B. A. C., Wolbink, G. J., Ophoff, R. A., Maehlen, M. T., van Riel, P., Merriman, M., Klareskog, L., Lie, B. A., Merriman, T., Crusius, J. B. A., Brouwer, E., Martin, J., de Vries, N., Toes, R., Padyukov, L., Koeleman, B. P. C., LifeLines Cohort Study, Genetica Groep Koeleman, Hersenen-Bedrijfsvoering, MMB, Child Health, Bossini-Castillo, L., de Kovel, C., Kallberg, H., van 't Slot, R., Italiaander, A., Coenen, M., Tak, P. P., Posthumus, M. D., Wijmenga, C., Huizinga, T., van der Helm-van Mil, A. H. M., Stoeken-Rijsbergen, G., Rodriguez-Rodriguez, Luis, Balsa, Alejandro, Gonzalez-Alvaro, Isidoro, Angel Gonzalez-Gay, Miguel, Gomez-Vaquero, Carmen, Franke, B., Vermeulen, S., van der Horst-Bruinsma, I. E., Dijkmans, B. A. C., Wolbink, G. J., Ophoff, R. A., Maehlen, M. T., van Riel, P., Merriman, M., Klareskog, L., Lie, B. A., Merriman, T., Crusius, J. B. A., Brouwer, E., Martin, J., de Vries, N., Toes, R., Padyukov, L., Koeleman, B. P. C., and LifeLines Cohort Study

Published
2015

45. Association of pain in knee osteoarthritis with distinct patterns of synovitis

Author

de Lange-Brokaar, B J E, Ioan-Facsinay, A, Yusuf, E, Visser, A W, Kroon, H M, van Osch, G J V M, Zuurmond, A-M, Stojanovic-Susulic, V, Bloem, J L, Nelissen, R G H H, Huizinga, T W, Kloppenburg, M, de Lange-Brokaar, B J E, Ioan-Facsinay, A, Yusuf, E, Visser, A W, Kroon, H M, van Osch, G J V M, Zuurmond, A-M, Stojanovic-Susulic, V, Bloem, J L, Nelissen, R G H H, Huizinga, T W, and Kloppenburg, M

Abstract

OBJECTIVE: To determine possible patterns of synovitis on contrast-enhanced magnetic resonance imaging (CE-MRI) and its relation to pain and severity in patients with radiographic knee osteoarthritis (OA).METHODS: In total, 86 patients (mean age 62 years, 66% women, median body mass index 29 kg/m(2) ) with symptomatic knee OA (Kellgren/Lawrence radiographic score 3) were included. T1-weighted, gadolinium-chelate-enhanced MRI with fat suppression was used to semiquantitatively score the extent of synovitis at 11 knee sites (total score range 0-22). Self-reported pain was assessed with 3 standardized questionnaires. Principal components analysis (PCA) was used to investigate patterns (the location and severity) of synovitis. Subsequently, these patterns were assessed for associations with pain measures and radiographic severity in adjusted logistic regression models.RESULTS: Synovitis was observed in 86 patients and was found to be generally mild on CE-MRI (median total synovitis score 7, range 0-16). The median pain scores were 53 (range 0-96) on the visual analog scale for pain, 51.4 (range 2.8-97.2) on the Knee Injury and Osteoarthritis Outcome Score (KOOS) for pain, 35 (range 0-75) on the Intermittent and Constant Osteoarthritis Pain (ICOAP) score for constant pain, and 40.6 (range 0-87.5) on the ICOAP score for intermittent pain. PCA resulted in extraction of 3 components, explaining 53.4% of the variance. Component 1 was characterized by synovitis at 7 sites (mainly medial parapatellar involvement) and was associated with scores on the KOOS pain subscale and the ICOAP constant pain subscale. Component 2 was characterized by synovitis at 4 sites (mainly the site adjacent to the anterior cruciate ligament), but was not associated with pain measures or with radiographic severity. Component 3, characterized by synovitis at 3 sites (mainly at the loose body site), was associated with radiographic severity.CONCLUSION: Different patterns of syno

Published
2015

46. Four-month metacarpal bone mineral density loss predicts radiological joint damage progression after 1 year in patients with early rheumatoid arthritis: exploratory analyses from the IMPROVED study

Author

Wevers-de Boer, K. V. C., Heimans, L., Visser, K., Kälvesten, Johan, Goekoop, R. J., van Oosterhout, M., Harbers, J. B., Bijkerk, C., Steup-Beekman, M., de Buck, M. P. D. M., de Sonnaville, P. B. J., Huizinga, T. W. J., Allaart, C. F., Wevers-de Boer, K. V. C., Heimans, L., Visser, K., Kälvesten, Johan, Goekoop, R. J., van Oosterhout, M., Harbers, J. B., Bijkerk, C., Steup-Beekman, M., de Buck, M. P. D. M., de Sonnaville, P. B. J., Huizinga, T. W. J., and Allaart, C. F.

Abstract

Aim To assess whether in early (rheumatoid) arthritis (RA) patients, metacarpal bone mineral density (BMD) loss after 4 months predicts radiological progression after 1 year of antirheumatic treatment. Methods Metacarpal BMD was measured 4 monthly during the first year by digital X-ray radiogrammetry (DXR-BMD) in patients participating in the IMPROVED study, a clinical trial in 610 patients with recent onset RA (2010 criteria) or undifferentiated arthritis, treated according to a remission (disease activity scoreless than1.6) steered strategy. With Sharp/van der Heijde progression greater than= 0.5 points after 1 year (yes/no) as dependent variable, univariate and multivariate logistic regression analyses were performed. Results Of 428 patients with DXR-BMD results and progression scores available, 28 (7%) had radiological progression after 1 year. Independent predictors for radiological progression were presence of baseline erosions (OR (95% CI) 6.5 (1.7 to 25)) and early DXR-BMD loss (OR (95% CI) 1.5 (1.1 to 2.0)). In 366 (86%) patients without baseline erosions, early DXR-BMD loss was the only independent predictor of progression (OR (95% CI) 2.0 (1.4 to 2.9)). Conclusions In early RA patients, metacarpal BMD loss after 4 months of treatment is an independent predictor of radiological progression after 1 year. In patients without baseline erosions, early metacarpal BMD loss is the main predictor of radiological progression., Funding Agencies|Abbott

Published
2015
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49. C1q deficient individuals have a wide variety of clinical presentation, quality of life and life expectancy

Author

van Schaarenburg, R. A., Schejbel, L., Truedsson, L., Topaloglu, R., Al-Mayouf, S. M., Riordan, A., Simon, A., Kallel-Sellami, M., Arkwright, P. D., Ahlin, A., Hagelberg, S., Nielsen, S., Shayesteh, Alexander, Morales, A., Tam, S., Genel, F., Berg, S., van den Berg, J. M., Kuijpers, T. W., Olsson, R., Huizinga, T. W. J., Lankester, A. C., Trouw, L. A., van Schaarenburg, R. A., Schejbel, L., Truedsson, L., Topaloglu, R., Al-Mayouf, S. M., Riordan, A., Simon, A., Kallel-Sellami, M., Arkwright, P. D., Ahlin, A., Hagelberg, S., Nielsen, S., Shayesteh, Alexander, Morales, A., Tam, S., Genel, F., Berg, S., van den Berg, J. M., Kuijpers, T. W., Olsson, R., Huizinga, T. W. J., Lankester, A. C., and Trouw, L. A.

Published
2014

50. MRI results from the AVERT study: a randomized, active-controlled trial to evaluate induction of remission and maintenance of drug-free remission using abatacept in combination with methotrexate or as monotherapy in patients with early RA

Author

Peterfy, C, Burmester, GR, Bykerk, V, Combe, B, Furst, D, Huizinga, T, Karyekar, C, Wong, D, Conaghan, P, Emery, P, Peterfy, C, Burmester, GR, Bykerk, V, Combe, B, Furst, D, Huizinga, T, Karyekar, C, Wong, D, Conaghan, P, and Emery, P

Published
2014

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