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1. Spontaneous spreading depolarizations originate subcortically in a novel mouse model of familial hemiplegic migraine type 2

Author

Nico A. Jansen, Chelsey Linnenbank, Maarten Schenke, Rob A. Voskuyl, Maria S. Jorge, Georgii Krivoshein, Cor Breukel, Margot M. Linssen, Jill W.C. Claassens, Conny Brouwers, Sandra H. van Heiningen, Anders Heuck, Karin Lykke-Hartmann, Else A. Tolner, and Arn M.J.M. van den Maagdenberg

Subjects
Spreading depolarization, Na+/K+-ATPase, Familial hemiplegic migraine, Knock-in mouse model, T345A, Sodium current, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

The mechanisms of initiation of spreading depolarization (SD) are understudied due to a paucity of disease models with spontaneously occurring events. We here present a novel mouse model of familial hemiplegic migraine type 2 (FHM2), expressing the missense T345A-mutated α2 subunit of the Na+/K+ adenosine triphosphatase pump (Atp1a2T345A). Homozygous Atp1a2T345A mice showed regular spontaneous SDs that exhibit a diurnal rhythm and typically originate from the hippocampus. Heterozygous Atp1a2T345A mice rarely exhibited spontaneous SDs and, for electrically induced SDs, only showed an increased propagation speed, whereas homozygotes showed both increased propagation and decreased threshold. Remarkably, despite hippocampal hyperexcitability, spontaneous SDs in Atp1a2T345A mice were only rarely associated with epileptic behavior, and seizure expression during kindling was decreased. Spontaneous SDs could be prevented by modulation of persistent sodium currents. Hippocampal SDs occurred in the presence of an NMDA-receptor antagonist, but these events did not reach the cortex, suggesting that initiation and propagation of SD depend on different mechanisms in this model.

Published
2024
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2. Methotrexate treatment hampers induction of vaccine-specific CD4 T cell responses in patients with IMID

Author

Sander W Tas, Joep Killestein, Joost Raaphorst, Taco W Kuijpers, Alexandre E Voskuyl, Gertjan Wolbink, Theo Rispens, Anneke J van der Kooi, Anja Ten Brinke, Karina de Leeuw, Abraham Rutgers, Juan J Garcia-Vallejo, Frederike J Bemelman, YK Onno Teng, Phyllis I Spuls, Mark Löwenberg, Jelle de Wit, Diane van der Woude, Marcel W Bekkenk, Luuk Wieske, Esther Brusse, Laura Boekel, Filip Eftimov, Eileen W Stalman, Maurice Steenhuis, Sofie Keijzer, Olvi Cristianawati, Koos P J van Dam, Adriaan G Volkers, Annelie H Musters, Nicoline F Post, Angela L Bosma, Marc L Hilhorst, Yosta Vegting, Bo Broens, Barbara Horváth, Annabel M Ruiter, Matthias H Busch, Dirk Jan Hijnen, Niels J M Verstegen, Pieter A van Doorn, Jan JGM Verschuuren, Laura Y L Kummer, Ruth R Hagen, Christine Kreher, Lisan H Kuijper, Mariël C Duurland, Veronique A L Konijn, Carolien E van de Sandt, Laura Fernández Blanco, Amélie Bos, Charlotte Menage, Tineke Jorritsma, Jet van den Dijssel, Rivka de Jongh, Tom Ashhurst, Marit J van Gils, Mathieu Claireaux, Sija Marieke van Ham, Renée CF van Allaart, Adája E Baars, George Elias, Cécile ACM van Els, H Stephan Goedee, Geert RAM D’Haens, Papay BP Jallah, Elham S Mirfazeli, Jim BD Keijser, Lotte van Ouwerkerk, Pieter van Paassen, Agner R Parra Sanchez, W Ludo van der Pol, Corine RG Schreurs, R Bart Takkenberg, and Koos AH Zwinderman

Subjects
Medicine
Abstract

Objectives Methotrexate (MTX) is one of the most commonly used medications to treat rheumatoid arthritis (RA). However, the effect of MTX treatment on cellular immune responses remains incompletely understood. This raises concerns about the vulnerability of these patients to emerging infections and following vaccination.Methods In the current study, we investigated the impact of MTX treatment in patients with immune-mediated inflammatory disease on B and CD4 T cell SARS-CoV-2 vaccination responses. Eighteen patients with RA and two patients with psoriatic arthritis on MTX monotherapy were included, as well as 10 patients with RA without immunosuppressive treatment, and 29 healthy controls. CD4 T and B cell responses were analysed 7 days and 3–6 months after two SARS-CoV-2 messenger RNA vaccinations. High-dimensional flow cytometry analysis was used to analyse fresh whole blood, an activation-induced marker assay to measure antigen-specific CD4 T cells, and spike probes to study antigen-specific B cells.Results Seven days following two SARS-CoV-2 vaccinations, total B and T cell counts were similar between MTX-treated patients and controls. In addition, spike-specific B cell frequencies were unaffected. Remarkably, the frequency of antigen-specific CD4 T cells was reduced in patients using MTX and correlated strongly with anti-RBD IgG antibodies. These results suggest that decreased CD4 T cell activity may result in slower vaccination antibody responses in MTX-treated patients.Conclusion Taken together, MTX treatment reduces vaccine-induced CD4 T cell activation, which correlates with lower antibody responses.Trial registration number NL8900.

Published
2024
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3. Intercurrent infection as a risk factor for disease flares in patients with systemic lupus erythematosus

Author

Alexandre E Voskuyl, Irene E M Bultink, Birgit I Lissenberg-Witte, Michel W P Tsang-A-Sjoe, and Fatma el Hadiyen

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

Objective To determine whether intercurrent infections are a risk factor for subsequent disease flares in systemic lupus erythematosus (SLE).Methods Demographic and clinical characteristics of 203 patients with SLE participating in the Amsterdam SLE cohort were collected at baseline and during follow-up. Collection of data on infections and SLE flares was registry-based and infections and flares were categorised as minor or major, based on predefined criteria. Proportional hazard models with recurrent events and time-varying covariates were used to estimate the HR of SLE flares.Results The incidence rates of major and minor infections were 5.3 per 100 patient years and 63.9 per 100 patient years, respectively. The incidence rates of flares were 3.6 and 15.1 per 100 patient years for major flares and minor flares, respectively.In the proportional hazard model, intercurrent infections (major and minor combined) were associated with the occurrence of SLE flares (major and minor combined; HR 1.9, 95% CI: 1.3 to 2.9). The hazard ratio for a major SLE flare following a major infection was 7.4 (95% CI: 2.2 to 24.6). Major infections were not associated with the occurrence of minor flares.Conclusions The results of the present study show that intercurrent infections are associated with subsequent SLE flares, which supports the hypothesis that infections may trigger SLE flares.

Published
2024
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5. Clinical and humoral response after SARS-CoV-2 breakthrough infection in patients receiving immunosuppressant therapy

Author

Stalman, Eileen W., Wieske, Luuk, Keijser, Jim B.D., van Dam, Koos P.J., Kummer, Laura Y.L., Wilbrink, Maarten F., van Kempen, Zoé L.E., Killestein, Joep, Volkers, Adriaan G., Tas, Sander W., Boekel, Laura, Wolbink, Gerrit J., van der Kooi, Anneke J., Raaphorst, Joost, Löwenberg, Mark, Takkenberg, R. Bart, D’Haens, Geert R.A.M., Spuls, Phyllis I., Bekkenk, Marcel W., Musters, Annelie H., Post, Nicoline F., Bosma, Angela L., Hilhorst, Marc L., Vegting, Yosta, Bemelman, Frederique J., Voskuyl, Alexandre E., Broens, Bo, Parra Sanchez, Agner, van Els, Cécile A.C. M., de Wit, Jelle, Rutgers, Abraham, de Leeuw, Karina, Horváth, Barbara, Verschuuren, Jan J.G.M., Ruiter, Annabel M., van Ouwerkerk, Lotte, van der Woude, Diane, Allaart, Renée C.F., Onno Teng, Y.K., van Paassen, Pieter, Busch, Matthias H., Brusse, Esther, van Doorn, Pieter A., Baars, Adája E., Hijnen, Dirkjan, Schreurs, Corine R.G., van der Pol, W. Ludo, Goedee, H. Stephan, Steenhuis, Maurice, Keijzer, Sofie, Cristianawati, Olvi, Brinke, Anja ten, Verstegen, Niels J.M., Zwinderman, Koos A.H., van Ham, S. Marieke, Rispens, Theo, Welkers, Matthijs R., Jonges, Marcel, Eftimov, Filip, and Kuijpers, Taco W.

Published
2024
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6. Risk loci involved in giant cell arteritis susceptibility: a genome-wide association study

Author

Callejas, José Luis, Caminal-Montero, Luis, Corbera-Bellalta, Marc, de Miguel, Eugenio, Díaz-López, J. Bernardino, García-Villanueva, María Jesús, Gómez-Vaquero, Carmen, Guijarro-Rojas, Mercedes, Hidalgo-Conde, Ana, Marí-Alfonso, Begoña, Martínez-Berriochoa, Agustín, Morado, Inmaculada C., Narváez, Javier, Ramentol-Sintas, Marc, Martínez-Zapico, Aleida, Martínez-Taboada, Víctor Manuel, Miranda-Filloy, José A., Monfort, Jordi, Pérez-Conesa, Mercedes, Prieto-González, Sergio, Raya, Enrique, Ríos-Fenández, Raquel, Sánchez-Martín, Julio, Sopeña, Bernardo, Tío, Laura, Unzurrunzaga, Ainhoa, Wordsworth, Oliver, Whitwell, Isobel, Brock, Jessica, Douglas, Victoria, Hettiarachchi, Chamila, Bartholomew, Jacqui, Jarrett, Stephen, Smithson, Gayle, Green, Michael, Brown, Pearl Clark, Lawson, Cathy, Gordon, Esther, Lane, Suzanne, Francis, Rebecca, Dasgupta, Bhaskar, Masunda, Bridgett, Calver, Jo, Patel, Yusuf, Thompson, Charlotte, Gregory, Louise, Levy, Sarah, Menon, Ajit, Thompson, Amy, Dyche, Lisa, Martin, Michael, Li, Charles, Laxminarayan, Ramasharan, Wilcox, Louise, de Guzman, Ralph, Isaacs, John, Lorenzi, Alice, Farley, Ross, Hinchcliffe-Hume, Helain, Bejarano, Victoria, Hope, Susan, Nandi, Pradip, Stockham, Lynne, Wilde, Catherine, Durrant, Donna, Lloyd, Mark, Ye, Chee-Seng, Stevens, Rob, Jilani, Amjad, Collins, David, Pegler, Suzannah, Rivett, Ali, Price, Liz, McHugh, Neil, Skeoch, Sarah, O'Kane, Diana, Kirkwood, Sue, Vadivelu, Saravanan, Pugmire, Susan, Sultan, Shabina, Dooks, Emma, Armstrong, Lisa, Sadik, Hala, Nandagudi, Anupama, Abioye, Tolu, Ramos, Angelo, Gumus, Steph, Sofat, Nidhi, Harrison, Abiola, Seward, Abi, Mollan, Susan, Rahan, Ray, Hawkins, Helen, Emsley, Hedley, Bhargava, Anna, Fleming, Vicki, Hare, Marianne, Raj, Sonia, George, Emmanuel, Allen, Nicola, Hunter, Karl, O'Sullivan, Eoin, Bird, Georgina, Magliano, Malgorzata, Manzo, Katarina, Sanghera, Bobbie, Hutchinson, David, Hammonds, Fiona, Sharma, Poonam, Cooper, Richard, McLintock, Graeme, Al-Saffar, Zaid S., Green, Mike, Elliott, Kerry, Neale, Tania, Mallinson, Janine, Lanyon, Peter, Pradere, Marie-Josephe, Jordan, Natasha, Htut, Ei Phyu, Mushapaidzi, Thelma, Abercrombie, Donna, Wright, Sam, Rowlands, Jane, Mukhtyar, Chetan, Kennedy, James, Makkuni, Damodar, Wilhelmsen, Elva, Kouroupis, Michael, John, Lily, Hughes, Rod, Walsh, Margaret, Buckley, Marie, Mackay, Kirsten, Camden-Woodley, Tracey, Redome, Joan, Pearce, Kirsty, Marianayagam, Thiraupathy, Cruz, Carina, Warner, Elizabeth, Atchia, Ishmael, Walker, Claire, Black, Karen, Duffy, Stacey, Fothergill, Lynda, Jefferey, Rebecca, Toomey, Jackie, Rhys-Dillon, Ceril, Pothecary, Carla, Green, Lauren, Toms, Tracey, Maher, Linda, Davis, Diana, Sayan, Amrinder, Thankachen, Mini, Abusalameh, Mahdi, Record, Jessica, Khan, Asad, Stafford, Sam, Hussein, Azza, Williams, Clare, Fletcher, Alison, Johson, Laura, Burnett, Richard, Moots, Robert, Frankland, Helen, Dale, James, Moar, Kirsten, Hollas, Carol, Parker, Ben, Ridings, Derek, Eapen, Sandhya, John, Sindhu, Robson, Jo, Guthrie, Lucy Belle, Fyfe, Rose, Tait, Moira, Marks, Jonathan, Gunter, Emma, Hernandez, Rochelle, Bhat, Smita, Johnston, Paul, Khurshid, Muhammad, Barclay, Charlotte, Kapur, Deepti, Jeffrey, Helen, Hughes, Anna, Slack, Lauren, Thomas, Eleri, Royon, Anna, Hall, Angela, King, Jon, Nyathi, Sindi, Morris, Vanessa, Castelino, Madhura, Hawkins, Ellie, Tomson, Linda, Singh, Animesh, Nunag, Annalyn, O'Connor, Stella, Rushby, Nathan, Hewitson, Nicola, O'Sunmboye, Kenny, Lewszuk, Adam, Boyles, Louise, Perry, Martin, Williams, Emma, Graver, Christine, Defever, Emmanuel, Kamanth, Sanjeet, Kay, Dominic, Ogor, Joe, Winter, Louise, Horton, Sarah, Welch, Gillian, Hollinshead, Kath, Peters, James, Labao, Julius, Dmello, Andrea, Dawson, Julie, Graham, Denise, De Lord, Denise, Deery, Jo, Hazelton, Tracy, Carette, Simon, Chung, Sharon, Cuthbertson, David, Forbess, Lindsy J., Gewurz-Singer, Ora, Hoffman, Gary S., Koening, Curry L., Maksimowicz-McKinnon, Kathleen M., McAlear, Carol A., Moreland, Larry W., Pagnoux, Christian, Seo, Philip, Specks, Ulrich, Spiera, Robert F., Sreih, Antoine, Warrington, Kenneth J., Monach, Paul A., Weisman, Michael, Borrego-Yaniz, Gonzalo, Ortiz-Fernández, Lourdes, Madrid-Paredes, Adela, Kerick, Martin, Hernández-Rodríguez, José, Mackie, Sarah L, Vaglio, Augusto, Castañeda, Santos, Solans, Roser, Mestre-Torres, Jaume, Khalidi, Nader, Langford, Carol A, Ytterberg, Steven, Beretta, Lorenzo, Govoni, Marcello, Emmi, Giacomo, Cimmino, Marco A, Witte, Torsten, Neumann, Thomas, Holle, Julia, Schönau, Verena, Pugnet, Gregory, Papo, Thomas, Haroche, Julien, Mahr, Alfred, Mouthon, Luc, Molberg, Øyvind, Diamantopoulos, Andreas P, Voskuyl, Alexandre, Daikeler, Thomas, Berger, Christoph T, Molloy, Eamonn S, Blockmans, Daniel, van Sleen, Yannick, Iles, Mark, Sorensen, Louise, Luqmani, Raashid, Reynolds, Gary, Bukhari, Marwan, Bhagat, Shweta, Ortego-Centeno, Norberto, Brouwer, Elisabeth, Lamprecht, Peter, Klapa, Sebastian, Salvarani, Carlo, Merkel, Peter A, Cid, María C, González-Gay, Miguel A, Morgan, Ann W, Martin, Javier, and Márquez, Ana

Published
2024
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8. Primary SARS-CoV-2 infection in patients with immune-mediated inflammatory diseases: long-term humoral immune responses and effects on disease activity

Author

van Dam, Koos P. J., Volkers, Adriaan G., Wieske, Luuk, Stalman, Eileen W., Kummer, Laura Y. L., van Kempen, Zoé L. E., Killestein, Joep, Tas, Sander W., Boekel, Laura, Wolbink, Gerrit J., van der Kooi, Anneke J., Raaphorst, Joost, Takkenberg, R. Bart, D’Haens, Geert R. A. M., Spuls, Phyllis I., Bekkenk, Marcel W., Musters, Annelie H., Post, Nicoline F., Bosma, Angela L., Hilhorst, Marc L., Vegting, Yosta, Bemelman, Frederike J., Voskuyl, Alexandre E., Broens, Bo, Sanchez, Agner Parra, van Els, Cécile A. C. M., de Wit, Jelle, Rutgers, Abraham, de Leeuw, Karina, Horváth, Barbara, Verschuuren, Jan J. G. M., Ruiter, Annabel M., van Ouwerkerk, Lotte, van der Woude, Diane, Allaart, Renée C. F., Teng, Y. K. Onno, van Paassen, Pieter, Busch, Matthias H., Jallah, Papay B. P., Brusse, Esther, van Doorn, Pieter A., Baars, Adája E., Hijnen, Dirk Jan, Schreurs, Corine R. G., van der Pol, W. Ludo, Goedee, H. Stephan, Steenhuis, Maurice, Keijzer, Sofie, Keijser, Jim B. D., Cristianawati, Olvi, ten Brinke, Anja, Verstegen, Niels J. M., van Ham, S. Marieke, Rispens, Theo, Kuijpers, Taco W., Löwenberg, Mark, and Eftimov, Filip

Published
2023
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10. Spontaneous and optogenetically induced cortical spreading depolarization in familial hemiplegic migraine type 1 mutant mice

Author

Inge C.M. Loonen, Rob A. Voskuyl, Maarten Schenke, Sandra H. van Heiningen, Arn M.J.M. van den Maagdenberg, and Else A. Tolner

Subjects
Behaviour, Cortical excitability, Cortical spreading depolarization, Mouse model, Optogenetics, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Mechanisms underlying the migraine aura are incompletely understood, which to large extent is related to a lack of models in which cortical spreading depolarization (CSD), the correlate of the aura, occurs spontaneously. Here, we investigated electrophysiological and behavioural CSD features in freely behaving mice expressing mutant CaV2.1 Ca2+ channels, either with the milder R192Q or the severer S218L missense mutation in the α1 subunit, known to cause familial hemiplegic migraine type 1 (FHM1) in patients. Very rarely, spontaneous CSDs were observed in mutant but never in wildtype mice. In homozygous Cacna1aR192Q mice exclusively single-wave CSDs were observed whereas heterozygous Cacna1aS218L mice displayed multiple-wave events, seemingly in line with the more severe clinical phenotype associated with the S218L mutation. Spontaneous CSDs were associated with body stretching, one-directional slow head turning, and rotating movement of the body. Spontaneous CSD events were compared with those induced in a controlled manner using minimally invasive optogenetics. Also in the optogenetic experiments single-wave CSDs were observed in Cacna1aR192Q and Cacna1aS218L mice (whereas the latter also showed multiple-wave events) with movements similar to those observed with spontaneous events. Compared to wildtype mice, FHM1 mutant mice exhibited a reduced threshold and an increased propagation speed for optogenetically induced CSD with a more profound CSD-associated dysfunction, as indicated by a prolonged suppression of transcallosal evoked potentials and a reduction of unilateral forepaw grip performance. When induced during sleep, the optogenetic CSD threshold was particularly lowered, which may explain why spontaneous CSD events predominantly occurred during sleep. In conclusion, our data show that key neurophysiological and behavioural features of optogenetically induced CSDs mimic those of rare spontaneous events in FHM1 R192Q and S218L mutant mice with differences in severity in line with FHM1 clinical phenotypes seen with these mutations.

Published
2024
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13. Differential expression pattern of Bcl-2 family members in B and T cells in systemic lupus erythematosus and rheumatoid arthritis

Author

K Kielbassa, L Van der Weele, AE Voskuyl, N de Vries, E Eldering, and TW Kuijpers

Subjects
Systemic lupus erythematosus, Rheumatoid arthritis, Apoptosis, Bcl-2 family member expression, Diseases of the musculoskeletal system, RC925-935
Abstract

Abstract Objective This study aimed to evaluate the expression level of anti-apoptotic Bcl-2 family proteins in B and T cells in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in relation to disease activity and the effect of various Bcl-2 family inhibitors (BH3 mimetics) as potential treatment. Methods We included 14 SLE patients, 12 RA patients, and 13 healthy controls to study anti-apoptotic Bcl-2, Bcl-XL, and Mcl-1 expression and cell survival in different B and T cell subsets using stimulation assays and intracellular flow cytometry. Effect of various BH3 mimetics was assessed by cell viability analyses. Results In SLE, significant differences in Bcl-2 family members were confined to the B cell compartment with decreased induction of Bcl-XL (p ≤ 0.05) and Mcl-1 (p ≤ 0.001) upon CpG stimulation. In RA, we did not observe any differences in expression levels of Bcl-2 family proteins. Expression patterns did not correlate with disease activity apart from decreased induction of Mcl-1 in B cells in active SLE. After in vitro stimulation with CpG, plasmablasts were more viable after treatment with three different BH3 mimetics compared to naïve or memory B cells in control and patient cells. After activation, Mcl-1 inhibition was most effective in reducing plasmablast and T cell viability, however, less in patients than controls. Conclusion Our study provides evidence for the increased differential expression pattern of Bcl-2 family members in B and T cell subsets of patients with SLE compared to controls. Tested BH3 mimetics showed higher efficacy in controls compared to both autoimmune diseases, though nonsignificant due to low patient numbers.

Published
2023
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15. mRNA-1273 vaccinated inflammatory bowel disease patients receiving TNF inhibitors develop broad and robust SARS-CoV-2-specific CD8+ T cell responses

Author

van Allaart, Renée CF., Baars, Adája E., Bekkenk, Marcel W., Bemelman, Frederike J., Boekel, Laura, Bos, Amélie V., Bosma, Angela L., Broens, Bo, Brusse, Esther, Busch, Matthias H., Cristianawati, Olvi, van Doorn, Pieter A., Elias, George, van Els, Cécile ACM., van Gils, Marit J., Goedee, H Stephan, Hijnen, Dirk Jan, Hilhorst, Marc L., Horváth, Barbara, Jallah, Papay BP., de Jongh, Rivka, Mirfazeli, Elham S., Musters, Annelie H., Keijser, Jim BD., van Kempen, Zoé LE., Killestein, Joep, Kreher, Christine, de Leeuw, Karina, van der Kooi, Anneke J., van Ouwerkerk, Lotte, van Paassen, Pieter, Cabeza, Virginia Palomares, Parra Sanchez, Agner R., Ludo van der Pol, W., Post, Nicoline F., Raaphorst, Joop, Ruiter, Annabel M., Rutgers, Abraham, Schreurs, Corine RG., Spuls, Phyllis I., Takkenberg, R Bart, Tas, Sander W., Teng, YK Onno, Vegting, Yosta, Verschuuren, Jan JGM., Voskuyl, Alexandre E., de Wit, Jelle, Wolbink, Gerrit J., van der Woude, Diane, Zwinderman, Koos AH., van den Dijssel, Jet, Duurland, Mariël C., Konijn, Veronique AL., Kummer, Laura YL., Hagen, Ruth R., Kuijper, Lisan H., Wieske, Luuk, van Dam, Koos PJ., Stalman, Eileen W., Steenhuis, Maurice, Geerdes, Dionne M., Mok, Juk Yee, Kragten, Angela HM., Menage, Charlotte, Koets, Lianne, Veldhuisen, Barbera, Verstegen, Niels JM., van der Schoot, C Ellen, van Esch, Wim JE., D'Haens, Geert RAM., Löwenberg, Mark, Volkers, Adriaan G., Rispens, Theo, Kuijpers, Taco W., Eftimov, Filip, van Gisbergen, Klaas PJM., van Ham, S Marieke, ten Brinke, Anja, and van de Sandt, Carolien E.

Published
2024
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17. [18F]Fluoride PET provides distinct information on disease activity in ankylosing spondylitis as compared to MRI and conventional radiography

Author

de Jongh, Jerney, Verweij, Nicki J. F., Yaqub, Maqsood, van Denderen, Christiaan J., van der Horst-Bruinsma, Irene E., Bot, Joost C. J., Boden, Bouke J. H., Hemke, Robert, Smithuis, Frank F., Lems, Willem F., Lammertsma, Adriaan A., Voskuyl, Alexandre E., Boers, Maarten, Zwezerijnen, Gerben J. C., and van der Laken, Conny J.

Published
2023
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18. Primary SARS-CoV-2 infection in patients with immune-mediated inflammatory diseases: long-term humoral immune responses and effects on disease activity

Author

Koos P. J. van Dam, Adriaan G. Volkers, Luuk Wieske, Eileen W. Stalman, Laura Y. L. Kummer, Zoé L. E. van Kempen, Joep Killestein, Sander W. Tas, Laura Boekel, Gerrit J. Wolbink, Anneke J. van der Kooi, Joost Raaphorst, R. Bart Takkenberg, Geert R. A. M. D’Haens, Phyllis I. Spuls, Marcel W. Bekkenk, Annelie H. Musters, Nicoline F. Post, Angela L. Bosma, Marc L. Hilhorst, Yosta Vegting, Frederike J. Bemelman, Alexandre E. Voskuyl, Bo Broens, Agner Parra Sanchez, Cécile A. C. M. van Els, Jelle de Wit, Abraham Rutgers, Karina de Leeuw, Barbara Horváth, Jan J. G. M. Verschuuren, Annabel M. Ruiter, Lotte van Ouwerkerk, Diane van der Woude, Renée C. F. Allaart, Y. K. Onno Teng, Pieter van Paassen, Matthias H. Busch, Papay B. P. Jallah, Esther Brusse, Pieter A. van Doorn, Adája E. Baars, Dirk Jan Hijnen, Corine R. G. Schreurs, W. Ludo van der Pol, H. Stephan Goedee, Maurice Steenhuis, Sofie Keijzer, Jim B. D. Keijser, Olvi Cristianawati, Anja ten Brinke, Niels J. M. Verstegen, S. Marieke van Ham, Theo Rispens, Taco W. Kuijpers, Mark Löwenberg, Filip Eftimov, and on behalf of the T2B! Immunity against SARS-CoV-2 study group

Subjects
SARS-CoV-2, Covid-19, Autoimmune disease, Immune-mediated inflammatory diseases, Immunosuppression, TNF, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressants (ISPs) may have impaired long-term humoral immune responses and increased disease activity after SARS-CoV-2 infection. We aimed to investigate long-term humoral immune responses against SARS-CoV-2 and increased disease activity after a primary SARS-CoV-2 infection in unvaccinated IMID patients on ISPs. Methods IMID patients on active treatment with ISPs and controls (i.e. IMID patients not on ISP and healthy controls) with a confirmed SARS-CoV-2 infection before first vaccination were included from an ongoing prospective cohort study (T2B! study). Clinical data on infections and increased disease activity were registered using electronic surveys and health records. A serum sample was collected before first vaccination to measure SARS-CoV-2 anti-receptor-binding domain (RBD) antibodies. Results In total, 193 IMID patients on ISP and 113 controls were included. Serum samples from 185 participants were available, with a median time of 173 days between infection and sample collection. The rate of seropositive IMID patients on ISPs was 78% compared to 100% in controls (p

Published
2023
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20. Post-COVID condition in patients with inflammatory rheumatic diseases: a prospective cohort study in the Netherlands

Author

Boekel, Laura, Atiqi, Sadaf, Leeuw, Maureen, Hooijberg, Femke, Besten, Yaëlle R., Wartena, Rosa, Steenhuis, Maurice, Vogelzang, Erik, Webers, Casper, Boonen, Annelies, Gerritsen, Martijn, Lems, Willem F, Tas, Sander W, van Vollenhoven, Ronald F, Voskuyl, Alexandre E, van der Horst-Bruinsma, Irene, Nurmohamed, Mike, Rispens, Theo, and Wolbink, Gertjan

Published
2023
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22. Web-based eHealth Clinical Decision Support System as a tool for the treat-to-target management of patients with systemic lupus erythematosus: development and initial usability evaluation

Author

Ronald van Vollenhoven, Alexandre Voskuyl, Agner Russo Parra Sanchez, Max G Grimberg, Myrthe Hanssen, Moon Aben, Elianne Jairth, Prishent Dhoeme, and Hendrik Jan Jansen

Subjects
Computer applications to medicine. Medical informatics, R858-859.7
Abstract

Background Treat-to-target (T2T) is a therapeutic strategy currently being studied for its application in systemic lupus erythematosus (SLE). Patients and rheumatologists have little support in making the best treatment decision in the context of a T2T strategy, thus, the use of information technology for systematically processing data and supporting information and knowledge may improve routine decision-making practices, helping to deliver value-based care.Objective To design and develop an online Clinical Decision Support Systems (CDSS) tool “SLE-T2T”, and test its usability for the implementation of a T2T strategy in the management of patients with SLE.Methods A prototype of a CDSS was conceived as a web-based application with the task of generating appropriate treatment advice based on entered patients’ data. Once developed, a System Usability Score (SUS) questionnaire was implemented to test whether the eHealth tool was user-friendly, comprehensible, easy-to-deliver and workflow-oriented. Data from the participants’ comments were synthesised, and the elements in need for improvement were identified.Results The beta version web-based system was developed based on the interim usability and acceptance evaluation. 7 participants completed the SUS survey. The median SUS score of SLE-T2T was 79 (scale 0 to 100), categorising the application as ‘good’ and indicating the need for minor improvements to the design.Conclusions SLE-T2T is the first eHealth tool to be designed for the management of SLE patients in a T2T context. The SUS score and unstructured feedback showed high acceptance of this digital instrument for its future use in a clinical trial.

Published
2023
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25. Breakthrough SARS-CoV-2 infections with the delta (B.1.617.2) variant in vaccinated patients with immune-mediated inflammatory diseases using immunosuppressants: a substudy of two prospective cohort studies

Author

de Jongh, Rivka, van de Sandt, Carolien, Kuijper, Lisan, Duurland, Mariel, Hagen, Ruth, van den Dijssel, Jet, Kreher, Christine, Bos, Amelie, Palomares Cabeza, Viriginia, Konijn, Veronique, Elias, George, Vallejo, Juan, van Gils, Marrit, Ashhurst, Tom, Nejentsev, Sergey, Mirfazeli, Elham, Boekel, Laura, Stalman, Eileen W, Wieske, Luuk, Hooijberg, Femke, van Dam, Koos P J, Besten, Yaëlle R, Kummer, Laura Y L, Steenhuis, Maurice, van Kempen, Zoé L E, Killestein, Joep, Volkers, Adriaan G, Tas, Sander W, van der Kooi, Anneke J, Raaphorst, Joost, Löwenberg, Mark, Takkenberg, R Bart, D'Haens, Geert R A M, Spuls, Phyllis I, Bekkenk, Marcel W, Musters, Annelie H, Post, Nicoline F, Bosma, Angela L, Hilhorst, Marc L, Vegting, Yosta, Bemelman, Frederike J, Voskuyl, Alexandre E, Broens, Bo, Parra Sanchez, Agner, van Els, Cécile A C M, de Wit, Jelle, Rutgers, Abraham, de Leeuw, Karina, Horváth, Barbara, Verschuuren, Jan J G M, Ruiter, Annabel M, van Ouwerkerk, Lotte, van der Woude, Diane, Allaart, Cornelia F, Teng, Y K Onno, van Paassen, Pieter, Busch, Matthias H, Jallah, Papay B P, Brusse, Esther, van Doorn, Pieter A, Baars, Adája E, Hijnen, Dirk Jan, Schreurs, Corine R G, van der Pol, W Ludo, Goedee, H Stephan, Vogelzang, Erik H, Leeuw, Maureen, Atiqi, Sadaf, van Vollenhoven, Ronald, Gerritsen, Martijn, van der Horst-Bruinsma, Irene E, Lems, Willem F, Nurmohamed, Mike T, Boers, Maarten, Keijzer, Sofie, Keijser, Jim, Boogaard, Arend, Cristianawati, Olvi, ten Brinke, Anja, Verstegen, Niels J M, Zwinderman, Koos A H, van Ham, S Marieke, Rispens, Theo, Kuijpers, Taco W, Wolbink, Gertjan, and Eftimov, Filip

Published
2022
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26. Physician Global Assessment International Standardisation COnsensus in Systemic Lupus Erythematosus: the PISCOS study

Author

Appenzeller, Simone, Aranow, Cynthia, Askanase, Anca, Avcin, Tadej, Bae, Sang-Cheol, Bertsias, George, Bonfa, Eloisa, Cairoli, Ernesto, Cardiel, Mario H, Cervera, Ricard, Chasset, François, Chizzolini, Carlo, Clarke, Ann E, Conti, Fabrizio, Costedoat-Chalumeau, Nathalie, Czirják, László, Doria, Andrea, Dörner, Thomas, Espinosa, Gerard, Fischer-Betz, Rebecca, Garcìa, Mercedes, Gladman, Dafna D, González, Luis A, Gunnarsson, Iva, Hamijoyo, Laniyati, Hanly, John G, Hasni, Sarfaraz A, Houssiau, Frédéric A, Inanç, Murat, Inês, Luís S, Isenberg, David, Jacobsen, Soren, Jan Wu, Yeong-Jian, Kaneko, Yuko, Katsumata, Yasuhiro, Lau, Chak S, Legge, Alexandra C, Lerang, Karoline, Limper, Maarten, Louthrenoo, Worawit, Luo, Shue-Fen, Marinho, António, Massardo, Loreto, Mathian, Alexis, Mosca, Marta, Nikpour, Mandana, Pego-Reigosa, José M, Peschken, Christine A, Pons-Estel, Bernardo A, Pons-Estel, Guillermo J, Rahman, Anisur, Rednic, Simona, Ribi, Camillo, Ruiz-Irastorza, Guillermo, Sato, Emilia I, Saxena, Amit, Schneider, Matthias, Sebastiani, Gian Domenico, Strand, Vibeke, Svenungsson, Elisabet, Tanaka, Yoshiya, Tazi Mezalek, Zoubida, Tee, Michael L, Tincani, Angela, Touma, Zahi, Troldborg, Anne, Vasconcelos, Carlos, Vinet, Évelyne, Vital, Edward M, Voskuyl, Alexandre E, Voss, Anne, Wallace, Daniel, Ward, Michael, Zamora, Leonid D, Piga, Matteo, Chessa, Elisabetta, Morand, Eric F, Ugarte-Gil, Manuel F, Tektonidou, Maria, van Vollenhoven, Ronald, Petri, Michelle, and Arnaud, Laurent

Published
2022
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28. Risk factors associated with short-term adverse events after SARS-CoV-2 vaccination in patients with immune-mediated inflammatory diseases

Author

Wieske, Luuk, Kummer, Laura Y. L., van Dam, Koos P. J., Stalman, Eileen W., van der Kooi, Anneke J., Raaphorst, Joost, Löwenberg, Mark, Takkenberg, R. Bart, Volkers, Adriaan G., D’Haens, Geert R. A. M., Tas, Sander W., Spuls, Phyllis I., Bekkenk, Marcel W., Musters, Annelie H., Post, Nicoline F., Bosma, Angela L., Hilhorst, Marc L., Vegting, Yosta, Bemelman, Frederike J., Killestein, Joep, van Kempen, Zoé L. E., Voskuyl, Alexandre E., Broens, Bo, Sanchez, Agner Parra, Wolbink, Gertjan, Boekel, Laura, Rutgers, Abraham, de Leeuw, Karina, Horváth, Barbara, Verschuuren, Jan J. G. M., Ruiter, Annabel M., van Ouwerkerk, Lotte, van der Woude, Diane, Allaart, Cornelia F., Teng, Y. K. Onno, van Paassen, Pieter, Busch, Matthias H., Jallah, B. Papay, Brusse, Esther, van Doorn, Pieter A., Baars, Adája E., Hijnen, Dirkjan, Schreurs, Corine R. G., van der Pol, W. Ludo, Goedee, H. Stephan, Steenhuis, Maurice, Rispens, Theo, ten Brinke, Anja, Verstegen, Niels J. M., Zwinderman, Koos A. H., van Ham, S. Marieke, Kuijpers, Taco W., and Eftimov, Filip

Published
2022
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29. Risk factors associated with short-term adverse events after SARS-CoV-2 vaccination in patients with immune-mediated inflammatory diseases

Author

Luuk Wieske, Laura Y. L. Kummer, Koos P. J. van Dam, Eileen W. Stalman, Anneke J. van der Kooi, Joost Raaphorst, Mark Löwenberg, R. Bart Takkenberg, Adriaan G. Volkers, Geert R. A. M. D’Haens, Sander W. Tas, Phyllis I. Spuls, Marcel W. Bekkenk, Annelie H. Musters, Nicoline F. Post, Angela L. Bosma, Marc L. Hilhorst, Yosta Vegting, Frederike J. Bemelman, Joep Killestein, Zoé L. E. van Kempen, Alexandre E. Voskuyl, Bo Broens, Agner Parra Sanchez, Gertjan Wolbink, Laura Boekel, Abraham Rutgers, Karina de Leeuw, Barbara Horváth, Jan J. G. M. Verschuuren, Annabel M. Ruiter, Lotte van Ouwerkerk, Diane van der Woude, Cornelia F. Allaart, Y. K. Onno Teng, Pieter van Paassen, Matthias H. Busch, B. Papay Jallah, Esther Brusse, Pieter A. van Doorn, Adája E. Baars, Dirkjan Hijnen, Corine R. G. Schreurs, W. Ludo van der Pol, H. Stephan Goedee, Maurice Steenhuis, Theo Rispens, Anja ten Brinke, Niels J. M. Verstegen, Koos A. H. Zwinderman, S. Marieke van Ham, Taco W. Kuijpers, Filip Eftimov, and on behalf of the T2B! immunity against SARS-CoV-2 study group

Subjects
Medicine
Abstract

Abstract Background Studies have suggested incremental short-term adverse events (AE) after repeated vaccination. In this report, we assessed occurrence and risk factors for short-term AEs following repeated SARS-CoV-2 vaccination in patients with various immune-mediated inflammatory diseases (IMIDs). Methods Self-reported daily questionnaires on AEs during the first 7 days after vaccination were obtained of 2259 individuals (2081 patients and 178 controls) participating in an ongoing prospective multicenter cohort study on SARS-CoV-2 vaccination in patients with various IMIDs in the Netherlands (T2B-COVID). Relative risks were calculated for potential risk factors associated with clinically relevant AE (rAE), defined as AE lasting longer than 2 days or impacting daily life. Results In total, 5454 vaccinations were recorded (1737 first, 1992 second and 1478 third vaccinations). Multiple sclerosis, Crohn’s disease and rheumatoid arthritis were the largest disease groups. rAEs were reported by 57.3% (95% CI 54.8–59.8) of patients after the first vaccination, 61.5% (95% CI 59.2–63.7) after the second vaccination and 58% (95% CI 55.3–60.6) after the third vaccination. At day 7 after the first, second and third vaccination, respectively, 7.6% (95% CI 6.3–9.1), 7.4% (95% CI 6.2–8.7) and 6.8% (95% CI 5.4–8.3) of patients still reported AEs impacting daily life. Hospital admissions and allergic reactions were uncommon (

Published
2022
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30. Humoral responses after second and third SARS-CoV-2 vaccination in patients with immune-mediated inflammatory disorders on immunosuppressants: a cohort study

Author

de Jongh, R., van de Sandt, C.E., Kuijper, L., Duurland, M., Hagen, R.R., van den Dijssel, J., Kreher, C., Bos, A., Palomares Cabeza, V., Konijn, V.A.L., Elias, G., Vallejo, J.G., van Gils, M.J., Ashhurst, T.M., Nejentsev, S., Mirfazeli, E.S., Wieske, Luuk, van Dam, Koos P J, Steenhuis, Maurice, Stalman, Eileen W, Kummer, Laura Y L, van Kempen, Zoé L E, Killestein, Joep, Volkers, Adriaan G, Tas, Sander W, Boekel, Laura, Wolbink, Gerrit J, van der Kooi, Anneke J, Raaphorst, Joost, Löwenberg, Mark, Takkenberg, R Bart, D'Haens, Geert R A M, Spuls, Phyllis I, Bekkenk, Marcel W, Musters, Annelie H, Post, Nicoline F, Bosma, Angela L, Hilhorst, Marc L, Vegting, Yosta, Bemelman, Frederike J, Voskuyl, Alexandre E, Broens, Bo, Sanchez, Agner Parra, van Els, Cécile A C M, de Wit, Jelle, Rutgers, Abraham, de Leeuw, Karina, Horváth, Barbara, Verschuuren, Jan J G M, Ruiter, Annabel M, van Ouwerkerk, Lotte, van der Woude, Diane, Allaart, Renée C F, Teng, Y K Onno, van Paassen, Pieter, Busch, Matthias H, Jallah, Papay B P, Brusse, Esther, van Doorn, Pieter A, Baars, Adája E, Hijnen, Dirk Jan, Schreurs, Corine R G, van der Pol, W Ludo, Goedee, H Stephan, Keijzer, Sofie, Keijser, Jim B D, Boogaard, Arend, Cristianawati, Olvi, ten Brinke, Anja, Verstegen, Niels J M, Zwinderman, Koos A H, van Ham, S Marieke, Kuijpers, Taco W, Rispens, Theo, and Eftimov, Filip

Published
2022
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31. Does Adding Single‐Nucleotide Polymorphisms to Risk Algorithms Improve Cardiovascular Disease Risk Prediction in Rheumatoid Arthritis? An Internal and External Validation of a Clinical Risk Score.

Author

Agca, Rabia, Popa, Calin D., Heymans, Martijn W., Crusius, Bart, Voskuyl, Alexandre E., and Nurmohamed, Michael T.

Subjects
DISEASE risk factors, SYSTOLIC blood pressure, LOGISTIC regression analysis, BODY mass index, SINGLE nucleotide polymorphisms
Abstract

Objective: Current risk algorithms do not accurately predict cardiovascular disease (CVD) risk in rheumatoid arthritis (RA). An area of interest is that of single‐nucleotide polymorphisms (SNPs), of which several have been associated with CVD in the general population. We investigated whether these SNPs are associated with CVD in RA and whether SNPs could improve CVD risk prediction in RA. Methods: Sixty SNPs were genotyped in 353 patients with RA. Logistic and Cox regression analyses were performed to identify SNPs that were associated with CVD (n = 99). A prediction model with clinical variables was made. SNPs were added to investigate the additional predictive value. Both models were internally validated. External validation was done in a separate cohort (n = 297). Results: rs3184504, rs4773144, rs12190287, and rs445925 were significantly associated with new CVD. The clinical prediction model consisted of age, sex, body mass index, systolic blood pressure, high‐density lipoprotein cholesterol (HDLc), and creatinine, with an area under the curve (AUC) of 0.74 (P = 0.03). Internal validation resulted in an AUC of 0.76 (P < 0.01). A new model was made including SNPs and resulted in a model with rs17011666 and rs801426, age, total cholesterol, and HDLc, which performed slightly better with an AUC of 0.77 (P < 0.01). External validation resulted in a good fit for the clinical model, but a poor fit for the SNP model. Conclusion: Several SNPs were associated with CVD in RA. Risk prediction slightly improved after adding SNPs to the models, but the clinical relevance is debatable. However, larger studies are needed to determine more accurately the additional value of these SNPs to CVD risk prediction algorithms. [ABSTRACT FROM AUTHOR]

Published
2024
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32. Evaluating the Construct of Damage in Systemic Lupus Erythematosus

Author

Johnson, Sindhu R., Gladman, Dafna D., Brunner, Hermine I., Isenberg, David, Clarke, Ann E., Barber, Megan R. W., Arnaud, Laurent, Fortin, Paul R., Mosca, Marta, Voskuyl, Alexandre E., Manzi, Susan, Aranow, Cynthia, Askanase, Anca, Alarcón, Graciela S., Bae, Sang‐Cheol, Costedoat‐Chalumeau, Nathalie, English, Jessica A., Pons‐Estel, Guillermo J., Pons‐Estel, Bernardo A., Gilman, Rebecca, Ginzler, Ellen M., Hanly, John G., Jacobsen, Soren, Kalunian, Kenneth, Kamen, Diane L., Lambalgen, Chynace, Legge, Alexandra, Lim, S. Sam, Mak, Anselm, Morand, Eric F., Peschken, Christine A., Petri, Michelle, Rahman, Anisur, Ramsey‐Goldman, Rosalind, Reynolds, John A., Romero‐Diaz, Juanita, Ruiz‐Irastorza, Guillermo, Sanchez‐Guerrero, Jorge, Svenungsson, Elisabet, Touma, Zahi, Urowitz, Murray, Vinet, Evelyne, van Vollenhoven, Ronald F., Waldhauser, Heather, Wallace, Daniel J., Zoma, Asad, and Bruce, Ian N.

Published
2023
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33. Antibody development after COVID-19 vaccination in patients with autoimmune diseases in the Netherlands: a substudy of data from two prospective cohort studies

Author

Boekel, Laura, Steenhuis, Maurice, Hooijberg, Femke, Besten, Yaëlle R, van Kempen, Zoé L E, Kummer, Laura Y, van Dam, Koos P J, Stalman, Eileen W, Vogelzang, Erik H, Cristianawati, Olvi, Keijzer, Sofie, Vidarsson, Gestur, Voskuyl, Alexandre E, Wieske, Luuk, Eftimov, Filip, van Vollenhoven, Ronald, Kuijpers, Taco W, van Ham, S Marieke, Tas, Sander W, Killestein, Joep, Boers, Maarten, Nurmohamed, Michael T, Rispens, Theo, and Wolbink, Gertjan

Published
2021
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37. Positron Emission Tomography to Improve Assessment of Interstitial Lung Disease in Patients With Systemic Sclerosis Eligible for Autologous Stem Cell Transplantation

Author

Bo Broens, Conny J. van der Laken, Gerben J.C. Zwezerijnen, Esther J. Nossent, Lilian J. Meijboom, Julia Spierings, Jeska K. de Vries-Bouwstra, Jacob M. van Laar, and Alexandre E. Voskuyl

Subjects
systemic sclerosis, scleroderma, interstitial lung disease, lung fibrosis, stem cell transplantation, positron emission tomography, Immunologic diseases. Allergy, RC581-607
Abstract

Positron emission tomography (PET) is a promising technique to improve the assessment of systemic sclerosis associated interstitial lung disease (SSc-ILD). This technique could be of particular value in patients with severe diffuse cutaneous SSc (dcSSc) that are possibly eligible for autologous hematopoietic stem cell transplantation (aHSCT). aHSCT is a potentially effective therapy for patients with severe dcSSc and ILD, leading to stabilization or improvement of lung function. However, there is a high need to improve patient selection, which includes (1) the selection of patients with rapidly progressive ILD for early rather than last-resort aHSCT (2) the prediction of treatment response on ILD and (3) the understanding of the mechanism(s) of action of aHSCT in the lungs. As previous studies with 18F-FDG PET in SSc-ILD and other forms of ILD have demonstrated its potential value in predicting disease progression and reactivity to anti-inflammatory treatment, we discuss the potential benefit of using this technique in patients with early severe dcSSc and ILD in the context of aHSCT. In addition, we discuss the potential value of other PET tracers in the assessment of ILD and understanding the mechanisms of action of aHSCT in the lung. Finally, we provide several suggestions for future research.

Published
2022
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38. Antibody development and disease severity of COVID-19 in non-immunised patients with rheumatic immune-mediated inflammatory diseases: data from a prospective cohort study

Author

Ronald F van Vollenhoven, Sander W Tas, Taco W Kuijpers, Maarten Boers, Michael T Nurmohamed, Gertjan Wolbink, Irene E van der Horst-Bruinsma, Theo Rispens, Willem Lems, Alexandre Voskuyl, Carla A Wijbrandts, S Marieke van Ham, Martijn Gerritsen, Erik H Vogelzang, Luuk Wieske, Laura Boekel, Femke Hooijberg, Yaëlle R Besten, Maureen Leeuw, Sadaf Atiqi, C Krieckaert, Bas Dijkshoorn, Siham Bakhlakh, Juliette J Crooijmans, Filip Eftimov, Laura Y Kummer, PJ Koos van Dam, Eileen W Stalman, Maurice Steenhuis, Sofie Keijzer, Olvi Cristianawati, Jim Keijser, and Floris C Loeff

Subjects
Medicine
Published
2022
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43. 2021 DORIS definition of remission in SLE: final recommendations from an international task force

Author

Victoria P Werth, Ronald F van Vollenhoven, Laurent Arnaud, Ricard Cervera, Andrea Doria, Angela Tincani, Matthias Schneider, Marta Mosca, Nathalie Costedoat-Chalumeau, Cynthia Aranow, Michelle A Petri, Ian N Bruce, Dimitrios T Boumpas, Michael M Ward, Manuel Francisco Ugarte-Gil, Bernardo A Pons-Estel, Ann Elaine Clarke, Juanita Romero-Diaz, Caroline Gordon, Sang-Cheol Bae, Anisur Rahman, Murat Inanc, Søren Jacobsen, George Bertsias, Xavier Mariette, Thomas Dörner, Hendrika Bootsma, Josef Smolen, Mandana Nikpour, David Jayne, Martin Aringer, David Isenberg, László Czirják, Annegret Kuhn, Y K Onno Teng, Frédéric A Houssiau, Hermine Brunner, Eric Morand, Carlos Vasconcelos, Guillermo Pons-Estel, Graciela Alarcon, Eloisa Bonfa, Alexandre Voskuyl, Raquel Faria, Anne Voss, Maarten Limper, Anca D Askanase, Sandra Navarra, Cindy Coney, Ruth Fritsch-Stork, Bernadette van Leeuw, Michel Tsang-a-Sjoe, Rebecca Fischer, Marzena Helena Olesinska, Blanca Rubio, Yehuda Schoenfeld, and Elena Zakharhova

Subjects
Immunologic diseases. Allergy, RC581-607
Published
2021
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45. Impact of glucocorticoids on the incidence of lupus-related major organ damage: a systematic literature review and meta-regression analysis of longitudinal observational studies

Author

Ronald F van Vollenhoven, Laurent Arnaud, Marta Mosca, Nathalie Costedoat-Chalumeau, Elisabet Svenungsson, Daniel J Wallace, Judith A James, Kenneth Kalunian, Susan Manzi, Michelle A Petri, Jill Buyon, Rosalind Ramsey-Goldman, Ian N Bruce, Guillermo Ruiz-Irastorza, Ellen M Ginzler, Manuel Francisco Ugarte-Gil, Bernardo A Pons-Estel, Juanita Romero-Diaz, Sang-Cheol Bae, Anisur Rahman, Paul R Fortin, Dafna D Gladman, Andreas Jönsen, Murat Inanc, Diane L Kamen, Søren Jacobsen, Jorge Sanchez-Guerrero, Évelyne Vinet, Murray Urowitz, David Isenberg, Sasha Bernatsky, John Reynolds, Eric Morand, Vernon Farewell, Claudia Elera-Fitzcarrald, Cristina Reátegui-Sokolova, Alexandre Voskuyl, Anca D Askanase, John Hanly, Anselm Mak, Sung Sam Lim, Christine Peschken, Graciela S. Alarcon, Joanna Leong, Bhushan Dharmadhikari, Nien Yee Kow, Cinthia Aranow, Mary Ann Dooley, and Mike Cheung

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

Objective In systemic lupus erythematosus (SLE), disease activity and glucocorticoid (GC) exposure are known to contribute to irreversible organ damage. We aimed to examine the association between GC exposure and organ damage occurrence.Methods We conducted a literature search (PubMed (Medline), Embase and Cochrane January 1966–October 2021). We identified original longitudinal observational studies reporting GC exposure as the proportion of users and/or GC use with dose information as well as the occurrence of new major organ damage as defined in the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. Meta-regression analyses were performed. Reviews, case-reports and studies with

Published
2021
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46. A randomised, open-label trial to assess the optimal treatment strategy in early diffuse cutaneous systemic sclerosis: the UPSIDE study protocol

Author

Vanessa Smith, Ellen De Langhe, Jacob M van Laar, Alexandre E Voskuyl, Madelon C Vonk, Roger Hesselstrand, Ulrich A Walker, Dirk M Wuttge, Reinhard E Voll, Arjan A van de Loosdrecht, Julia Spierings, Joerg Henes, Anna van Rhenen, Paco MW Welsing, Anne CA Marijnissen, Nicoletta Del Papa, Daan Dierickx, Karina R Gheorghe, Tessa Kerre, Per Ljungman, Erik WAF Marijt, Miro Mayer, Marc Schmalzing, Roland Schroers, and Jeska K de Vries-Bouwstra

Subjects
Medicine
Abstract

Introduction Systemic sclerosis (SSc) is a chronic, autoimmune connective tissue disease associated with high morbidity and mortality, especially in diffuse cutaneous SSc (dcSSc). Currently, there are several treatments available in early dcSSc that aim to change the disease course, including immunosuppressive agents and autologous haematopoietic stem cell transplantation (HSCT). HSCT has been adopted in international guidelines and is offered in current clinical care. However, optimal timing and patient selection for HSCT are still unclear. In particular, it is unclear whether HSCT should be positioned as upfront therapy or rescue treatment for patients refractory to immunosuppressive therapy. We hypothesise that upfront HSCT is superior and results in lower toxicity and lower long-term medical costs. Therefore, we propose this randomised trial aiming to determine the optimal treatment strategy for early dcSSc by comparing two strategies used in standard care: (1) upfront autologous HSCT versus (2) immunosuppressive therapy (intravenous cyclophosphamide pulse therapy followed by mycophenolate mofetil) with rescue HSCT in case of treatment failure.Methods and analysis The UPSIDE (UPfront autologous hematopoietic Stem cell transplantation vs Immunosuppressive medication in early DiffusE cutaneous systemic sclerosis) study is a multicentre, randomised, open-label, controlled trial. In total, 120 patients with early dcSSc will be randomised. The primary outcome is event-free survival at 2 years after randomisation. Secondary outcomes include serious adverse events, functional status and health-related quality of life. We will also evaluate changes in nailfold capillaroscopy pattern, pulmonary function, cardiac MR and high-resolution CT of the chest. Follow-up visits will be scheduled 3-monthly for 2 years and annually in the following 3 years.Ethics and dissemination The study was approved by the Dutch Central Committee on Research Concerning Human Subjects (NL72607.041.20). The results will be disseminated through patient associations and conventional scientific channels.Trial registration numbers NCT04464434; NL 8720.

Published
2021
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48. Persistence of seroconversion at 6 months following primary immunisation in patients with immune-mediated inflammatory diseases

Author

Wieske, L., Stalman, E.W., Dam, P.J.K. van, Kummer, L.Y., Steenhuis, M., Kempen, Z.L.E. van, Killestein, J., Volkers, A.G., Tas, S.W., Boekel, L., Wolbink, G., Kooi, A. van der, Raaphorst, J., Lowenberg, M., Takkenberg, B., D'Haens, G.R.A.M., Spuls, P.I., Bekkenk, M.W., Musters, A.H., Post, N.F., Bosma, A.L., Hilhorst, M.L., Vegting, Y., Bemelman, F.J., Voskuyl, A., Broens, B., Sanchez, A.P., Els, C.A.C.M. van, Wit, J. de, Rutgers, A., Leeuw, K. de, Horvath, B., Verschuuren, J.J.G.M., Ruiter, A.M., Ouwerkerk, L. van, Woude, D. van der, Allaart, C.F., Teng, Y.K.O., Paassen, P. van, Busch, M.H., Jallah, P.B.P., Brusse, E., Doorn, P.A. van, Baars, A.E., Hijnen, D., Schreurs, C.R.G., Pol, W.L. van der, Goedee, H.S., Keijzer, S., Keijser, J., Cristianawati, O., Brinke, A. ten, Verstegen, N.J.M., Zwinderman, K.A.H., Ham, S.M. van, Kuijpers, T.W., Rispens, T., Eftimov, F., T2B Immunity SARS CoV 2 Study Grp, Interne Geneeskunde, MUMC+: MA Nefrologie (9), MUMC+: MA Klinische Immunologie (9), RS: Carim - B02 Vascular aspects thrombosis and Haemostasis, Neurology, Amsterdam Neuroscience - Neuroinfection & -inflammation, AII - Inflammatory diseases, Rheumatology, Dermatology, Nephrology, and AII - Infectious diseases

Subjects
Rheumatology, SDG 3 - Good Health and Well-being, Immunology, Vaccination, Immunology and Allergy, Tumor Necrosis Factor Inhibitors, Covid-19, General Biochemistry, Genetics and Molecular Biology, Autoimmune Diseases
Abstract

Patients with immune-mediated inflammatory diseases (IMIDs) may have impaired initial humoral responses after SARS-CoV-2 vaccination depending on the type of immunosuppression (ISP) used.1 It is largely unknown how antibody titres develop over time and whether it is needed to adjust timing of booster campaigns for patients with IMID.

Published
2023
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50. Synthesis and preliminary preclinical evaluation of fluorine-18 labelled isatin-4-(4-methoxyphenyl)-3-thiosemicarbazone ([18F]4FIMPTC) as a novel PET tracer of P-glycoprotein expression

Author

Joost Verbeek, Jonas Eriksson, Stina Syvänen, Marc Huisman, Robert C. Schuit, Carla F. M. Molthoff, Rob A. Voskuyl, Elizabeth C. de Lange, Adriaan A. Lammertsma, and Albert D. Windhorst

Subjects
P-glycoprotein, P-gp inhibitor, [18F]4FIMPTC, Radiofluorination, [18F]-fluorisatin, Medical physics. Medical radiology. Nuclear medicine, R895-920, Therapeutics. Pharmacology, RM1-950
Abstract

Abstract Background Several P-glycoprotein (P-gp) substrate tracers are available to assess P-gp function in vivo, but attempts to develop a tracer for measuring expression levels of P-gp have not been successful. Recently, (Z)-2-(5-fluoro-2-oxoindolin-3-ylidene)-N-(4-methoxyphenyl)hydrazine-carbothioamide was described as a potential selective P-gp inhibitor that is not transported by P-gp. Therefore, the purpose of this study was to radiolabel two of its analogues and to assess their potential for imaging P-gp expression using PET. Results [18F]2-(4-fluoro-2-oxoindolin-3-ylidene)-N-(4-methoxyphenyl)hydrazine-carbothioamide ([18F]5) and [18F]2-(6-fluoro-2-oxoindolin-3-ylidene)-N-(4-methoxyphenyl)hydrazine-carbothioamide ([18F]6) were synthesized and both their biodistribution and metabolism were evaluated in rats. In addition, PET scans were acquired in rats before and after tariquidar (P-gp inhibitor) administration as well as in P-gp knockout (KO) mice. Both [18F]5 and [18F]6 were synthesized in 2–3% overall yield, and showed high brain uptake in ex vivo biodistribution studies. [18F]6 appeared to be metabolically unstable in vivo, while [18F]5 showed moderate stability with limited uptake of radiolabelled metabolites in the brain. PET studies showed that transport of [18F]5 across the blood-brain barrier was not altered by pre-treatment with the P-gp inhibitor tariquidar, and uptake was significantly lower in P-gp KO than in wild-type animals and indeed transported across the BBB or bound to P-gp in endothelial cells. Conclusion In conclusion, [18F]5 and [18F]6 were successfully and reproducibly synthesized, albeit with low radiochemical yields. [18F]5 appears to be a radiotracer that binds to P-gp, as showed in P-gp knock-out animals, but is not a substrate for P-gp.

Published
2018
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