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1. A protein-truncating R179X variant in RNF186 confers protection against ulcerative colitis.

Author

Rivas, Manuel, Graham, Daniel, Sulem, Patrick, Stevens, Christine, Desch, A, Goyette, Philippe, Gudbjartsson, Daniel, Jonsdottir, Ingileif, Thorsteinsdottir, Unnur, Degenhardt, Frauke, Mucha, Sören, Kurki, Mitja, Li, Dalin, DAmato, Mauro, Annese, Vito, Vermeire, Severine, Weersma, Rinse, Halfvarson, Jonas, Paavola-Sakki, Paulina, Lappalainen, Maarit, Lek, Monkol, Cummings, Beryl, Tukiainen, Taru, Haritunians, Talin, Halme, Leena, Koskinen, Lotta, Ananthakrishnan, Ashwin, Luo, Yang, Heap, Graham, Visschedijk, Marijn, MacArthur, Daniel, Neale, Benjamin, Ahmad, Tariq, Anderson, Carl, Brant, Steven, Duerr, Richard, Silverberg, Mark, Cho, Judy, Palotie, Aarno, Saavalainen, Päivi, Kontula, Kimmo, Färkkilä, Martti, McGovern, Dermot, Franke, Andre, Stefansson, Kari, Rioux, John, Xavier, Ramnik, Daly, Mark, Barrett, J, de Lane, K, Edwards, C, Hart, A, Hawkey, C, Jostins, L, Kennedy, N, Lamb, C, Lee, J, Lees, C, Mansfield, J, Mathew, C, Mowatt, C, Newman, B, Nimmo, E, Parkes, M, Pollard, M, Prescott, N, Randall, J, Rice, D, Satsangi, J, Simmons, A, Tremelling, M, Uhlig, H, Wilson, D, Abraham, C, Achkar, J, Bitton, A, Boucher, G, Croitoru, K, Fleshner, P, Glas, J, Kugathasan, S, Limbergen, J, Milgrom, R, Proctor, D, Regueiro, M, Schumm, P, Sharma, Y, Stempak, J, Targan, S, and Wang, M

Subjects
Alleles, Colitis, Ulcerative, Genetic Association Studies, Genetic Predisposition to Disease, Genetic Testing, Humans, Mutation, Protein Transport, RNA, Messenger, Reproducibility of Results, Sequence Analysis, DNA, Ubiquitin-Protein Ligases
Abstract

Protein-truncating variants protective against human disease provide in vivo validation of therapeutic targets. Here we used targeted sequencing to conduct a search for protein-truncating variants conferring protection against inflammatory bowel disease exploiting knowledge of common variants associated with the same disease. Through replication genotyping and imputation we found that a predicted protein-truncating variant (rs36095412, p.R179X, genotyped in 11,148 ulcerative colitis patients and 295,446 controls, MAF=up to 0.78%) in RNF186, a single-exon ring finger E3 ligase with strong colonic expression, protects against ulcerative colitis (overall P=6.89 × 10(-7), odds ratio=0.30). We further demonstrate that the truncated protein exhibits reduced expression and altered subcellular localization, suggesting the protective mechanism may reside in the loss of an interaction or function via mislocalization and/or loss of an essential transmembrane domain.

Published
2016

2. Haematopoietic stem cell transplantation for severe autoimmune diseases in children: A review of current literature, registry activity and future directions on behalf of the autoimmune diseases and paediatric diseases working parties of the European Society for Blood and Marrow Transplantation

Author

Achini-Gutzwiller, F, Snowden, J, Corbacioglu, S, Greco, R, Alexander, T, Badoglio, M, Labopin, M, Abinun, M, Apte, S, Arnold, R, Domenech, A, Brierley, C, Burman, J, Castilla-Llorente, C, Cooper, N, Daghia, G, Daikeler, T, del Papa, N, de Vries-Bouwstra, J, Farge, D, Finke, J, Hagglund, H, Hawkey, C, Henes, J, Hiepe, F, Jessop, H, Kiely, D, Kazmi, M, Kirgizov, K, Kramer, E, Mancardi, G, Marjanovic, Z, Martin, R, Martin, T, Ma, D, Moore, J, Miller, P, Muraro, P, Oliveira, M, Polushin, A, Onida, F, Simoes, B, Puyade, M, Resnick, I, Ricart, E, Rovira, M, Saccardi, R, Saif, M, Sakellari, I, Sharrack, B, Snarski, E, Scherer, H, Sossa, C, Withers, B, Wulffraat, N, Zaccara, E, Amrolia, P, Ansari, M, Balduzzi, A, Dalassier, A, Dalle, J, Diaz, C, Feuchtinger, T, Locatelli, F, Lucchini, G, Galimard, J, Vincent, M, Handgretinger, R, Kleinschmidt, K, Lawitschka, A, Martinez, A, Peters, C, Rocha, V, Ruggeri, A, Sedlacek, P, Svec, P, Toporski, J, Yesilipek, A, Achini-Gutzwiller F. R., Snowden J. A., Corbacioglu S., Greco R., Alexander T., Snowden J., Badoglio M., Labopin M., Abinun M., Apte S., Arnold R., Domenech A., Brierley C., Burman J., Castilla-Llorente C., Cooper N., Daghia G., Daikeler T., del Papa N., de Vries-Bouwstra J., Farge D., Finke J., Hagglund H., Hawkey C., Henes J., Hiepe F., Jessop H., Kiely D., Kazmi M., Kirgizov K., Kramer E., Mancardi G., Marjanovic Z., Martin R., Martin T., Ma D., Moore J., Miller P., Muraro P., Oliveira M. -C., Polushin A., Onida F., Simoes B., Puyade M., Resnick I., Ricart E., Rovira M., Saccardi R., Saif M., Sakellari I., Sharrack B., Snarski E., Scherer H. U., Sossa C., Withers B., Wulffraat N., Zaccara E., Amrolia P., Ansari M., Balduzzi A., Dalassier A., Dalle J. -H., Diaz C. H., Feuchtinger T., Locatelli F., Lucchini G., Galimard J. -E., Vincent M. G., Handgretinger R., Kleinschmidt K., Lawitschka A., Martinez A. P., Peters C., Rocha V., Ruggeri A., Sedlacek P., Svec P., Toporski J., Yesilipek A., Achini-Gutzwiller, F, Snowden, J, Corbacioglu, S, Greco, R, Alexander, T, Badoglio, M, Labopin, M, Abinun, M, Apte, S, Arnold, R, Domenech, A, Brierley, C, Burman, J, Castilla-Llorente, C, Cooper, N, Daghia, G, Daikeler, T, del Papa, N, de Vries-Bouwstra, J, Farge, D, Finke, J, Hagglund, H, Hawkey, C, Henes, J, Hiepe, F, Jessop, H, Kiely, D, Kazmi, M, Kirgizov, K, Kramer, E, Mancardi, G, Marjanovic, Z, Martin, R, Martin, T, Ma, D, Moore, J, Miller, P, Muraro, P, Oliveira, M, Polushin, A, Onida, F, Simoes, B, Puyade, M, Resnick, I, Ricart, E, Rovira, M, Saccardi, R, Saif, M, Sakellari, I, Sharrack, B, Snarski, E, Scherer, H, Sossa, C, Withers, B, Wulffraat, N, Zaccara, E, Amrolia, P, Ansari, M, Balduzzi, A, Dalassier, A, Dalle, J, Diaz, C, Feuchtinger, T, Locatelli, F, Lucchini, G, Galimard, J, Vincent, M, Handgretinger, R, Kleinschmidt, K, Lawitschka, A, Martinez, A, Peters, C, Rocha, V, Ruggeri, A, Sedlacek, P, Svec, P, Toporski, J, Yesilipek, A, Achini-Gutzwiller F. R., Snowden J. A., Corbacioglu S., Greco R., Alexander T., Snowden J., Badoglio M., Labopin M., Abinun M., Apte S., Arnold R., Domenech A., Brierley C., Burman J., Castilla-Llorente C., Cooper N., Daghia G., Daikeler T., del Papa N., de Vries-Bouwstra J., Farge D., Finke J., Hagglund H., Hawkey C., Henes J., Hiepe F., Jessop H., Kiely D., Kazmi M., Kirgizov K., Kramer E., Mancardi G., Marjanovic Z., Martin R., Martin T., Ma D., Moore J., Miller P., Muraro P., Oliveira M. -C., Polushin A., Onida F., Simoes B., Puyade M., Resnick I., Ricart E., Rovira M., Saccardi R., Saif M., Sakellari I., Sharrack B., Snarski E., Scherer H. U., Sossa C., Withers B., Wulffraat N., Zaccara E., Amrolia P., Ansari M., Balduzzi A., Dalassier A., Dalle J. -H., Diaz C. H., Feuchtinger T., Locatelli F., Lucchini G., Galimard J. -E., Vincent M. G., Handgretinger R., Kleinschmidt K., Lawitschka A., Martinez A. P., Peters C., Rocha V., Ruggeri A., Sedlacek P., Svec P., Toporski J., and Yesilipek A.

Abstract

Although modern clinical management strategies have improved the outcome of paediatric patients with severe autoimmune and inflammatory diseases over recent decades, a proportion will experience ongoing or recurrent/relapsing disease activity despite multiple therapies often leading to irreversible organ damage, and compromised quality of life, growth/development and long-term survival. Autologous and allogeneic haematopoietic stem cell transplantation (HSCT) have been used successfully to induce disease control and often apparent cure of severe treatment-refractory autoimmune diseases (ADs) in children. However, transplant-related outcomes are disease-dependent and long-term outcome data are limited in respect to efficacy and safety. Moreover, balancing risks of HSCT against AD prognosis with continually evolving non-transplant options is challenging. This review appraises published literature on HSCT strategies and outcomes in individual paediatric ADs. We also provide a summary of the European Society for Blood and Marrow Transplantation (EBMT) Registry, where 343 HSCT procedures (176 autologous and 167 allogeneic) have been reported in 326 children (<18 years) for a range of AD indications. HSCT is a promising treatment modality, with potential long-term disease control or cure, but therapy-related morbidity and mortality need to be reduced. Further research is warranted to establish the position of HSCT in paediatric ADs via registries and prospective clinical studies to support evidence-based interspeciality guidelines and recommendations.

Published
2022

3. Haematopoietic stem cell transplantation for severe autoimmune diseases in children : a review of current literature, registry activity and future directions on behalf of the autoimmune diseases and paediatric diseases working parties of the European Society for Blood and Marrow Transplantation

Author

Achini‐Gutzwiller, FR, Snowden, JA, Corbacioglu, S, Greco, R, Alexander, T, Snowden, J, Badoglio, M, Labopin, M, Abinun, M, Apte, S, Arnold, R, Domenech, A, Brierley, C, Burman, J, Castilla‐Llorente, C, Cooper, N, Daghia, G, Daikeler, T, del Papa, N, de Vries‐Bouwstra, J, Farge, D, Finke, J, Hagglund, H, Hawkey, C, Henes, J, Hiepe, F, Jessop, H, Kiely, D, Kazmi, M, Kirgizov, K, Kramer, E, Mancardi, G, Marjanovic, Z, Martin, R, Martin, T, Ma, D, Moore, J, Miller, P, Muraro, P, Oliveira, M, Polushin, A, Onida, F, Simoes, B, Puyade, M, Resnick, I, Ricart, E, Rovira, M, Saccardi, R, Saif, M, Sakellari, I, Sharrack, B, Snarski, E, Scherer, HU, Sossa, C, Withers, B, Wulffraat, N, Zaccara, E, Amrolia, P, Ansari, M, Balduzzi, A, Dalassier, A, Dalle, J, Diaz, CH, Feuchtinger, T, Locatelli, F, Lucchini, G, Galimard, J, Vincent, MG, Handgretinger, R, Kleinschmidt, K, Lawitschka, A, Martinez, AP, Peters, C, Rocha, V, Ruggeri, A, Sedlacek, P, Svec, P, Toporski, J, Yesilipek, A, Achini-Gutzwiller, F, Snowden, J, Corbacioglu, S, Greco, R, Alexander, T, Badoglio, M, Labopin, M, Abinun, M, Apte, S, Arnold, R, Domenech, A, Brierley, C, Burman, J, Castilla-Llorente, C, Cooper, N, Daghia, G, Daikeler, T, del Papa, N, de Vries-Bouwstra, J, Farge, D, Finke, J, Hagglund, H, Hawkey, C, Henes, J, Hiepe, F, Jessop, H, Kiely, D, Kazmi, M, Kirgizov, K, Kramer, E, Mancardi, G, Marjanovic, Z, Martin, R, Martin, T, Ma, D, Moore, J, Miller, P, Muraro, P, Oliveira, M, Polushin, A, Onida, F, Simoes, B, Puyade, M, Resnick, I, Ricart, E, Rovira, M, Saccardi, R, Saif, M, Sakellari, I, Sharrack, B, Snarski, E, Scherer, H, Sossa, C, Withers, B, Wulffraat, N, Zaccara, E, Amrolia, P, Ansari, M, Balduzzi, A, Dalassier, A, Dalle, J, Diaz, C, Feuchtinger, T, Locatelli, F, Lucchini, G, Galimard, J, Vincent, M, Handgretinger, R, Kleinschmidt, K, Lawitschka, A, Martinez, A, Peters, C, Rocha, V, Ruggeri, A, Sedlacek, P, Svec, P, Toporski, J, and Yesilipek, A

Subjects
autoimmune diseases, haematopoietic stem cell transplantation, paediatric, ddc:610, paediatric, surgical procedures, operative, Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA, haematopoietic stem cell transplantation, 610 Medizin, autoimmune diseases, autoimmune disease, Hematology
Abstract

Although modern clinical management strategies have improved the outcome of paediatric patients with severe autoimmune and inflammatory diseases over recent decades, a proportion will experience ongoing or recurrent/relapsing disease activity despite multiple therapies often leading to irreversible organ damage, and compromised quality of life, growth/development and long-term survival. Autologous and allogeneic haematopoietic stem cell transplantation (HSCT) have been used successfully to induce disease control and often apparent cure of severe treatment-refractory autoimmune diseases (ADs) in children. However, transplant-related outcomes are disease-dependent and long-term outcome data are limited in respect to efficacy and safety. Moreover, balancing risks of HSCT against AD prognosis with continually evolving non-transplant options is challenging. This review appraises published literature on HSCT strategies and outcomes in individual paediatric ADs. We also provide a summary of the European Society for Blood and Marrow Transplantation (EBMT) Registry, where 343 HSCT procedures (176 autologous and 167 allogeneic) have been reported in 326 children (

Published
2022

4. Helicobacter pylori eradication for primary prevention of peptic ulcer bleeding in older patients prescribed aspirin (HEAT): a randomised placebo-controlled trial in primary care

Author

Hawkey, C, Avery, A, Coupland, CAC, and Hobbs, F

Abstract

Background Peptic ulcers in patients receiving aspirin are associated with Helicobacter pylori infection. We aimed to investigate whether H pylori eradication would protect against aspirin-associated ulcer bleeding. Methods We conducted a randomised, double-blind, placebo-controlled trial (Helicobacter Eradication Aspirin Trial [HEAT]) at 1208 primary care centres in the UK, using routinely collected clinical data. Eligible patients were aged 60 years or older who were receiving aspirin at a daily dose of 325 mg or less (with four or more 28-day prescriptions in the past year) and had a positive C13 urea breath test for H pylori at screening. Patients receiving ulcerogenic or gastroprotective medication were excluded. Participants were randomly assigned (1:1) to receive either a combination of oral clarithromycin 500 mg, metronidazole 400 mg, and lansoprazole 30 mg (active eradication), or oral placebo (control), twice daily for 1 week. Participants, their general practitioners and health-care providers, and the research nurses, trial team, adjudication committee, and analysis team were all masked to group allocation throughout the trial. Follow-up was by scrutiny of electronic data in primary and secondary care. The primary outcome was time to hospitalisation or death due to definite or probable peptic ulcer bleeding, and was analysed by Cox proportional hazards methods in the intention-to-treat population. This trial is registered with EudraCT, 2011-003425-96. Findings Between Sept 14, 2012, and Nov 22, 2017, 30 166 patients had breath testing for H pylori, 5367 had a positive result, and 5352 were randomly assigned to receive active eradication (n=2677) or placebo (n=2675) and were followed up for a median of 5·0 years (IQR 3·9–6·4). Analysis of the primary outcome showed a significant departure from proportional hazards assumptions (p=0·0068), requiring analysis over separate time periods. There was a significant reduction in incidence of the primary outcome in the active eradication group in the first 2·5 years of follow-up compared with the control group (six episodes adjudicated as definite or probable peptic ulcer bleeds, rate 0·92 [95% CI 0·41–2·04] per 1000 person-years vs 17 episodes, rate 2·61 [1·62–4·19] per 1000 person-years; hazard ratio [HR] 0·35 [95% CI 0·14–0·89]; p=0·028). This advantage remained significant after adjusting for the competing risk of death (p=0·028) but was lost with longer follow-up (HR 1·31 [95% CI 0·55–3·11] in the period after the first 2·5 years; p=0·54). Reports of adverse events were actively solicited; taste disturbance was the most common event (787 patients). Interpretation H pylori eradication protects against aspirin-associated peptic ulcer bleeding, but this might not be sustained in the long term. Funding National Institute for Health and Care Research Health Technology Assessment.

Published
2022
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5. Helicobacter pylori eradication for primary prevention of peptic ulcer bleeding in older patients prescribed aspirin (HEAT): a randomised placebo-controlled trial in primary care

Author

Hawkey, C J, Avery, Anthony J, Coupland, Carol A C, Crooks, Colin J, Dumbleton, Jennifer S, Hobbs, F D Richard, Kendrick, Denise, Moore, Michael, Morris, Clive, Rubin, Gregory, Smith, Murray D, and Stevenson, Diane

Abstract

Background: Peptic ulcers in patients on aspirin are associated with Helicobacter pylori infection. We investigated whether H. pylori eradication would protect against aspirin associated ulcer bleeding Methods: The Helicobacter Eradication Aspirin Trial (HEAT) was a randomised placebo-controlled trial (EudraCT 2011-003425-96), conducted in UK primary care using routinely collected clinical data. Consenting patients aged >60 years prescribed aspirin < 325 mg but not ulcerogenic or gastroprotective medication underwent C13 urea breath testing for H. pylori. Those with a positive test were randomised to receive either a combination of clarithromycin 500mg, metronidazole 400 mg and lansoprazole 30mg, or placebos twice daily for seven days . Follow up was by scrutiny of electronic data in primary and secondary care. The primary outcome, time to hospitalisation due to definite or probable peptic ulcer bleeding, was analysed by Cox proportional hazards methods

Published
2022

6. Author Correction: Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease (Nature Communications, (2020), 11, 1, (995), 10.1038/s41467-019-14275-y)

Author

Serra E. G., Schwerd T., Moutsianas L., Cavounidis A., Fachal L., Pandey S., Kammermeier J., Croft N. M., Posovszky C., Rodrigues A., Russell R. K., Barakat F., Auth M. K. H., Heuschkel R., Zilbauer M., Fyderek K., Braegger C., Travis S. P., Satsangi J., Parkes M., Thapar N., Ferry H., Matte J. C., Gilmour K. C., Wedrychowicz A., Sullivan P., Moore C., Sambrook J., Ouwehand W., Roberts D., Danesh J., Baeumler T. A., Fulga T. A., Carrami E. M., Ahmed A., Wilson R., Barrett J. C., Elkadri A., Griffiths A. M., Zurek M., Strisciuglio C., Elawad M., Lo B., Arancibia-Carcamo C., Bailey A., Barnes E., Bird-Lieberman E. L., Brain O., Braden B., Collier J., East J., Howarth L., Keshav S., Klenerman P., Leedham S., Palmer R., Powrie F., Simmons A., Walker M., Tolkien Z., Kaptoge S., Allen D., Mehenny S., Mant J., Di Angelantonio E., Thompson S. G., Yilmaz B., Juillerat P., Geuking M., Wiest R., Macpherson A. J., Bravo F. D., Brugger L., Carstens O., Bigler U. G., Heimgartner B., Rusticeanu M., Schmid-Uebelhart S., Strebel B., Tatu A., Tutuian R., Oyas O., Ramon C., Stelling J., Franc Y., Fournier N., Pittet V. E. H., Burnand B., Egger M., Golay D., Marot A., Musso L., Rossel J. -B., Seematter V., Sommer J., Vulliamy R., Michetti P., Maillard M. H., Keller C., Nydegger A., Schoepfe A., Archanioti E., Ezri J., Fraga M., Schoepfer A., Muller C., Rogler G., Biedermann L., Blattmann M., Burk S., Dora B., Fried M., Misselwitz B., Mullhaupt B., Obialo N., Pohl D., Raschle N., Scharl M., Vavricka S., Von Kanel R., Zeitz J., Abdelrahman K., Ademi G., Borovicka J., Brand S., Frei R., Haarer J., Knellwolf-Grieger C., Krieger-Grubel C., Kunzler P., Meyenberger C., Meyer P., Rohrich N., Sawatzki M., Schelling M., Semadeni G. -M., Sulz M., Zimmermann D., Aepli P., Criblez D. H., Hess C., Richterich J. -P., Spalinger J., Staudenmann D., Stulz A., Wohrle S., Thomas A., Anderegg C., Kohler H., Kusche R., Antonino A. -T., Arrigoni E., Bengoa J. M., Cunningham S., de Saussure P., Girard L., de Jong D. B., Basturk P., Brunner S., Degen L., Hruz P., Bakker C. K. -D., Niess J., Balsiger B., Haldemann J., Saner G., Seibold F., Bauerfeind P., Becocci A., Belli D., Binek J., Hengstler P., Boehm S., Boldanov T., Buhr P., Koller R., Rueger V., Senning A., Burri E., Buyse S., Cao D. -T., D'Angelo F., Delarive J., Doerig C., Hessler R., Preissler C., Rentsch R., Risti B., Ritz M. A., Steuerwald M., Vogtlin J., Sagmeister M., Sauter B., Schibli S., Sokollik C., Schlauri H., Schnegg J. -F., Seirafi M., Spangenberger H., Stadler P., Staub P., Stenz V., Tempia-Caliera M., Thorens J., Truninger K., Urfer P., Viani F., Vouillamoz D., Zander S., Wyli T., Jostins L., Kennedy N. A., Ahmad T., Lamb C. A., Edwards C., Hart A., Hawkey C., Mansfield J. C., Mowat C., Newman W. G., Tremelling M., Lee J. C., Prescott N. J., Mathew C. G., Lees C. W., McGovern D. P. B., Targan S. R., Botwin G., Mengesha E., Fleshner P., Landers C., Li D., Rioux J. D., Bitton A., Cote-Daigneault J., Daly M. J., Xavier R., Morris K., Boucher G., Cho J. H., Abraham C., Merad M., Sands B., Peter I., Hao K., Itan Y., Duerr R. H., Konnikova L., Schwartz M. B., Proksell S., Johnston E., Miladinova V., Chen W., Brant S. R., Datta L., Silverberg M. S., Schumm L. P., Birch S., Giri M., Gettler K., Sharma Y., Stevens C., Lazarev M., Haritunians T., Snapper S. B., Shah N., Muise A. M., Wilson D. C., Uhlig H. H., Anderson C. A., Serra, E. G., Schwerd, T., Moutsianas, L., Cavounidis, A., Fachal, L., Pandey, S., Kammermeier, J., Croft, N. M., Posovszky, C., Rodrigues, A., Russell, R. K., Barakat, F., Auth, M. K. H., Heuschkel, R., Zilbauer, M., Fyderek, K., Braegger, C., Travis, S. P., Satsangi, J., Parkes, M., Thapar, N., Ferry, H., Matte, J. C., Gilmour, K. C., Wedrychowicz, A., Sullivan, P., Moore, C., Sambrook, J., Ouwehand, W., Roberts, D., Danesh, J., Baeumler, T. A., Fulga, T. A., Carrami, E. M., Ahmed, A., Wilson, R., Barrett, J. C., Elkadri, A., Griffiths, A. M., Zurek, M., Strisciuglio, C., Elawad, M., Lo, B., Arancibia-Carcamo, C., Bailey, A., Barnes, E., Bird-Lieberman, E. L., Brain, O., Braden, B., Collier, J., East, J., Howarth, L., Keshav, S., Klenerman, P., Leedham, S., Palmer, R., Powrie, F., Simmons, A., Walker, M., Tolkien, Z., Kaptoge, S., Allen, D., Mehenny, S., Mant, J., Di Angelantonio, E., Thompson, S. G., Yilmaz, B., Juillerat, P., Geuking, M., Wiest, R., Macpherson, A. J., Bravo, F. D., Brugger, L., Carstens, O., Bigler, U. G., Heimgartner, B., Rusticeanu, M., Schmid-Uebelhart, S., Strebel, B., Tatu, A., Tutuian, R., Oyas, O., Ramon, C., Stelling, J., Franc, Y., Fournier, N., Pittet, V. E. H., Burnand, B., Egger, M., Golay, D., Marot, A., Musso, L., Rossel, J. -B., Seematter, V., Sommer, J., Vulliamy, R., Michetti, P., Maillard, M. H., Keller, C., Nydegger, A., Schoepfe, A., Archanioti, E., Ezri, J., Fraga, M., Schoepfer, A., Muller, C., Rogler, G., Biedermann, L., Blattmann, M., Burk, S., Dora, B., Fried, M., Misselwitz, B., Mullhaupt, B., Obialo, N., Pohl, D., Raschle, N., Scharl, M., Vavricka, S., Von Kanel, R., Zeitz, J., Abdelrahman, K., Ademi, G., Borovicka, J., Brand, S., Frei, R., Haarer, J., Knellwolf-Grieger, C., Krieger-Grubel, C., Kunzler, P., Meyenberger, C., Meyer, P., Rohrich, N., Sawatzki, M., Schelling, M., Semadeni, G. -M., Sulz, M., Zimmermann, D., Aepli, P., Criblez, D. H., Hess, C., Richterich, J. -P., Spalinger, J., Staudenmann, D., Stulz, A., Wohrle, S., Thomas, A., Anderegg, C., Kohler, H., Kusche, R., Antonino, A. -T., Arrigoni, E., Bengoa, J. M., Cunningham, S., de Saussure, P., Girard, L., de Jong, D. B., Basturk, P., Brunner, S., Degen, L., Hruz, P., Bakker, C. K. -D., Niess, J., Balsiger, B., Haldemann, J., Saner, G., Seibold, F., Bauerfeind, P., Becocci, A., Belli, D., Binek, J., Hengstler, P., Boehm, S., Boldanov, T., Buhr, P., Koller, R., Rueger, V., Senning, A., Burri, E., Buyse, S., Cao, D. -T., D'Angelo, F., Delarive, J., Doerig, C., Hessler, R., Preissler, C., Rentsch, R., Risti, B., Ritz, M. A., Steuerwald, M., Vogtlin, J., Sagmeister, M., Sauter, B., Schibli, S., Sokollik, C., Schlauri, H., Schnegg, J. -F., Seirafi, M., Spangenberger, H., Stadler, P., Staub, P., Stenz, V., Tempia-Caliera, M., Thorens, J., Truninger, K., Urfer, P., Viani, F., Vouillamoz, D., Zander, S., Wyli, T., Jostins, L., Kennedy, N. A., Ahmad, T., Lamb, C. A., Edwards, C., Hart, A., Hawkey, C., Mansfield, J. C., Mowat, C., Newman, W. G., Tremelling, M., Lee, J. C., Prescott, N. J., Mathew, C. G., Lees, C. W., Mcgovern, D. P. B., Targan, S. R., Botwin, G., Mengesha, E., Fleshner, P., Landers, C., Li, D., Rioux, J. D., Bitton, A., Cote-Daigneault, J., Daly, M. J., Xavier, R., Morris, K., Boucher, G., Cho, J. H., Abraham, C., Merad, M., Sands, B., Peter, I., Hao, K., Itan, Y., Duerr, R. H., Konnikova, L., Schwartz, M. B., Proksell, S., Johnston, E., Miladinova, V., Chen, W., Brant, S. R., Datta, L., Silverberg, M. S., Schumm, L. P., Birch, S., Giri, M., Gettler, K., Sharma, Y., Stevens, C., Lazarev, M., Haritunians, T., Snapper, S. B., Shah, N., Muise, A. M., Wilson, D. C., Uhlig, H. H., and Anderson, C. A.

Published
2022

8. OP021 Autologous haematopoietic stem cell transplantation for Crohn’s disease: a retrospective study from the European Society for Blood & Marrow Transplantation (EBMT) Autoimmune Diseases Working Party

Author

Brierley, C, Castilla-Llorente, C, Labopin, M, Badoglio, M, Rovira, M, Ricart, E, Dierickx, D, Vermeire, S, Hasselblatt, P, Finke, J, Onida, F, Cassinotti, A, Satsangi, J, Kazmi, M, López-Sanromán, A, Farge, D, Travis, S, Hawkey, C, and Snowden, J

Published
2018
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13. Haematopoietic stem cell transplantation for severe autoimmune diseases in children: A review of current literature, registry activity and future directions on behalf of the autoimmune diseases and paediatric diseases working parties of the European Society for Blood and Marrow Transplantation

Author

Achini-Gutzwiller, F. R., Snowden, J. A., Corbacioglu, S., Greco, R., Alexander, T., Snowden, J., Badoglio, M., Labopin, M., Abinun, M., Apte, S., Arnold, R., Domenech, A., Brierley, C., Burman, J., Castilla-Llorente, C., Cooper, N., Daghia, G., Daikeler, T., del Papa, N., de Vries-Bouwstra, J., Farge, D., Finke, J., Hagglund, H., Hawkey, C., Henes, J., Hiepe, F., Jessop, H., Kiely, D., Kazmi, M., Kirgizov, K., Kramer, E., Mancardi, G., Marjanovic, Z., Martin, R., Martin, T., Ma, D., Moore, J., Miller, P., Muraro, P., Oliveira, M. -C., Polushin, A., Onida, F., Simoes, B., Puyade, M., Resnick, I., Ricart, E., Rovira, M., Saccardi, R., Saif, M., Sakellari, I., Sharrack, B., Snarski, E., Scherer, H. U., Sossa, C., Withers, B., Wulffraat, N., Zaccara, E., Amrolia, P., Ansari, M., Balduzzi, A., Dalassier, A., Dalle, J. -H., Diaz, C. H., Feuchtinger, T., Locatelli, Franco, Lucchini, G., Galimard, J. -E., Vincent, M. G., Handgretinger, R., Kleinschmidt, K., Lawitschka, A., Martinez, A. P., Peters, C., Rocha, V., Ruggeri, A., Sedlacek, P., Svec, P., Toporski, J., Yesilipek, A., Locatelli F. (ORCID:0000-0002-7976-3654), Achini-Gutzwiller, F. R., Snowden, J. A., Corbacioglu, S., Greco, R., Alexander, T., Snowden, J., Badoglio, M., Labopin, M., Abinun, M., Apte, S., Arnold, R., Domenech, A., Brierley, C., Burman, J., Castilla-Llorente, C., Cooper, N., Daghia, G., Daikeler, T., del Papa, N., de Vries-Bouwstra, J., Farge, D., Finke, J., Hagglund, H., Hawkey, C., Henes, J., Hiepe, F., Jessop, H., Kiely, D., Kazmi, M., Kirgizov, K., Kramer, E., Mancardi, G., Marjanovic, Z., Martin, R., Martin, T., Ma, D., Moore, J., Miller, P., Muraro, P., Oliveira, M. -C., Polushin, A., Onida, F., Simoes, B., Puyade, M., Resnick, I., Ricart, E., Rovira, M., Saccardi, R., Saif, M., Sakellari, I., Sharrack, B., Snarski, E., Scherer, H. U., Sossa, C., Withers, B., Wulffraat, N., Zaccara, E., Amrolia, P., Ansari, M., Balduzzi, A., Dalassier, A., Dalle, J. -H., Diaz, C. H., Feuchtinger, T., Locatelli, Franco, Lucchini, G., Galimard, J. -E., Vincent, M. G., Handgretinger, R., Kleinschmidt, K., Lawitschka, A., Martinez, A. P., Peters, C., Rocha, V., Ruggeri, A., Sedlacek, P., Svec, P., Toporski, J., Yesilipek, A., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

Although modern clinical management strategies have improved the outcome of paediatric patients with severe autoimmune and inflammatory diseases over recent decades, a proportion will experience ongoing or recurrent/relapsing disease activity despite multiple therapies often leading to irreversible organ damage, and compromised quality of life, growth/development and long-term survival. Autologous and allogeneic haematopoietic stem cell transplantation (HSCT) have been used successfully to induce disease control and often apparent cure of severe treatment-refractory autoimmune diseases (ADs) in children. However, transplant-related outcomes are disease-dependent and long-term outcome data are limited in respect to efficacy and safety. Moreover, balancing risks of HSCT against AD prognosis with continually evolving non-transplant options is challenging. This review appraises published literature on HSCT strategies and outcomes in individual paediatric ADs. We also provide a summary of the European Society for Blood and Marrow Transplantation (EBMT) Registry, where 343 HSCT procedures (176 autologous and 167 allogeneic) have been reported in 326 children (<18 years) for a range of AD indications. HSCT is a promising treatment modality, with potential long-term disease control or cure, but therapy-related morbidity and mortality need to be reduced. Further research is warranted to establish the position of HSCT in paediatric ADs via registries and prospective clinical studies to support evidence-based interspeciality guidelines and recommendations.

Published
2022

40. Retinoid Toxicity

Author

Turton, J. A., primary, Hicks, R. M., additional, Gwynne, J., additional, Hunt, R., additional, and Hawkey, C. M., additional

Published
2008
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