Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Expert recommendation
  • Published:

Precision medicine in monogenic inflammatory bowel disease: proposed mIBD REPORT standards

Nature Reviews Gastroenterology & Hepatology volume 20, pages 810–828 (2023)Cite this article

Subjects

Abstract

Owing to advances in genomics that enable differentiation of molecular aetiologies, patients with monogenic inflammatory bowel disease (mIBD) potentially have access to genotype-guided precision medicine. In this Expert Recommendation, we review the therapeutic research landscape of mIBD, the reported response to therapies, the medication-related risks and systematic bias in reporting. The mIBD field is characterized by the absence of randomized controlled trials and is dominated by retrospective observational data based on case series and case reports. More than 25 off-label therapeutics (including small-molecule inhibitors and biologics) as well as cellular therapies (including haematopoietic stem cell transplantation and gene therapy) have been reported. Heterogeneous reporting of outcomes impedes the generation of robust therapeutic evidence as the basis for clinical decision making in mIBD. We discuss therapeutic goals in mIBD and recommend standardized reporting (mIBD REPORT (monogenic Inflammatory Bowel Disease Report Extended Phenotype and Outcome of Treatments) standards) to stratify patients according to a genetic diagnosis and phenotype, to assess treatment effects and to record safety signals. Implementation of these pragmatic standards should help clinicians to assess the therapy responses of individual patients in clinical practice and improve comparability between observational retrospective studies and controlled prospective trials, supporting future meta-analysis.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Proposed mechanisms of action for targeted therapies in mIBD.
Fig. 2: Examples of precision medicine in four mIBD groups.
Fig. 3: Therapeutic studies in mIBD and the mIBD REPORT standards.

Similar content being viewed by others

References

  1. Uhlig, H. H. et al. Clinical genomics for the diagnosis of monogenic forms of inflammatory bowel disease: a position paper from the Paediatric IBD Porto group of European Society of Paediatric Gastroenterology, Hepatology and Nutrition. J. Pediatr. Gastroenterol. Nutr. 72, 456–473 (2021).

    PubMed  PubMed Central  Google Scholar 

  2. Bolton, C. et al. An integrated taxonomy for monogenic inflammatory bowel disease. Gastroenterology 122, 859–876 (2022).

    Google Scholar 

  3. Uhlig, H. H. & Powrie, F. Translating immunology into therapeutic concepts for inflammatory bowel disease. Annu. Rev. Immunol. 36, 755–781 (2018).

    CAS  PubMed  Google Scholar 

  4. Charbit-Henrion, F., Parlato, M., Malamut, G., Ruemmele, F. & Cerf-Bensussan, N. Intestinal immunoregulation: lessons from human mendelian diseases. Mucosal Immunol. 14, 1017–1037 (2021).

    CAS  PubMed  Google Scholar 

  5. Sullivan, K. E., Conrad, M. & Kelsen, J. R. Very early-onset inflammatory bowel disease: an integrated approach. Curr. Opin. Allergy Clin. Immunol. 18, 459–469 (2018).

    PubMed  PubMed Central  Google Scholar 

  6. Ouahed, J. et al. Very early onset inflammatory bowel disease: a clinical approach with a focus on the role of genetics and underlying immune deficiencies. Inflamm. Bowel Dis. 26, 820–842 (2020).

    PubMed  Google Scholar 

  7. Kammermeier, J. et al. Genomic diagnosis and care co-ordination for monogenic inflammatory bowel disease in children and adults: consensus guideline on behalf of the British Society of Gastroenterology and British Society of Paediatric Gastroenterology, Hepatology and Nutrition. Lancet Gasteroenterol. Hepatol. 8, 271–286 (2023).

    Google Scholar 

  8. Crowley, E. et al. Prevalence and clinical features of inflammatory bowel diseases associated with monogenic variants, identified by whole-exome sequencing in 1000 children at a single center. Gastroenterology 158, 2208–2220 (2020).

    CAS  PubMed  Google Scholar 

  9. Nambu, R. et al. A systematic review of monogenic inflammatory bowel disease. Clin. Gastroenterol. Hepatol. 20, e653–e663 (2022).

    CAS  PubMed  Google Scholar 

  10. Crowley, E. et al. Impact of drug approval pathways for paediatric inflammatory bowel disease. J. Crohns Colitis 23, 331–335 (2021).

    Google Scholar 

  11. Both, T. et al. Inflammatory bowel disease in primary immunodeficiency disorders is a heterogeneous clinical entity requiring an individualized treatment strategy: a systematic review. Autoimmun. Rev. 20, 102872 (2021).

    CAS  PubMed  Google Scholar 

  12. Boztug, K. et al. Stem-cell gene therapy for the Wiskott–Aldrich syndrome. N. Engl. J. Med. 363, 1918–1927 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Kawai, T. et al. A gene therapy clinical study of a patient with X-linked chronic granulomatous disease. Mol. Ther. 24, S87–S88 (2016).

    Google Scholar 

  14. Kohn, D. B. et al. Lentiviral gene therapy for X-linked chronic granulomatous disease. Nat. Med. 26, 200–206 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Glocker, E.-O. et al. Infant colitis – it’s in the genes. Lancet 376, 1272 (2010).

    PubMed  Google Scholar 

  16. Glocker, E. O. et al. Inflammatory bowel disease and mutations affecting the interleukin-10 receptor. N. Engl. J. Med. 361, 2033–2045 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Forbes, L. R. et al. Jakinibs for the treatment of immune dysregulation in patients with gain-of-function signal transducer and activator of transcription 1 (STAT1) or STAT3 mutations. J. Allergy Clin. Immunol. 142, 1665–1669 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Rudra, S. et al. Ruxolitinib: targeted approach for treatment of autoinflammatory very early onset inflammatory bowel disease. Clin. Gastroenterol. Hepatol. 20, 1408–1410 (2022).

    CAS  PubMed  Google Scholar 

  19. Geerlinks, A. V., Dvorak, A. M. & XIAP Deficiency Treatment Consortium. A case of XIAP deficiency successfully managed with tadekinig alfa (rhIL-18BP). J. Clin. Immunol. 42, 901–903 (2022).

    PubMed  Google Scholar 

  20. Egg, D. et al. Therapeutic options for CTLA-4 insufficiency. J. Allergy Clin. Immunol. 149, 736–746 (2022).

    CAS  PubMed  Google Scholar 

  21. Kammermeier, J. et al. Phenotypic and genotypic characterisation of inflammatory bowel disease presenting before the age of 2 years. J. Crohns Colitis 11, 60–69 (2017).

    PubMed  Google Scholar 

  22. Torres, J. et al. ECCO guidelines on therapeutics in Crohn’s disease: medical treatment. J. Crohns Colitis 14, 4–22 (2020).

    PubMed  Google Scholar 

  23. Raine, T. et al. ECCO guidelines on therapeutics in ulcerative colitis: medical treatment. J. Crohns Colitis 16, 2–17 (2022).

    PubMed  Google Scholar 

  24. Passerini, L. et al. Treatment with rapamycin can restore regulatory T-cell function in IPEX patients. J. Allergy Clin. Immunol. 145, 1262–1271.e13 (2020).

    CAS  PubMed  Google Scholar 

  25. Azizi, G. et al. New therapeutic approach by sirolimus for enteropathy treatment in patients with LRBA deficiency. Eur. Ann. Allergy Clin. Immunol. 49, 235–239 (2017).

    CAS  PubMed  Google Scholar 

  26. Maccari, M. E. et al. Disease evolution and response to rapamycin in activated phosphoinositide 3-kinase δ syndrome: the European Society for Immunodeficiencies–Activated Phosphoinositide 3-Kinase δ Syndrome Registry. Front. Immunol. 9, 543 (2018).

    PubMed  PubMed Central  Google Scholar 

  27. Gruber, C. N. et al. Complex autoinflammatory syndrome unveils fundamental principles of JAK1 kinase transcriptional and biochemical function. Immunity 53, 672 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Talbot, J. W. et al. Management of enteritis associated with tricohepatoenteric syndrome due to SKIV2L mutation using the combination of JAK1/2 inhibition and azathioprine. JPGN Rep. 3, e264 (2022).

    PubMed  PubMed Central  Google Scholar 

  29. Ye, Z. et al. Clinical and genetic spectrum of children with congenital diarrhea and enteropathy in China. Genet. Med. 21, 2224–2230 (2019).

    PubMed  Google Scholar 

  30. Noel, N. et al. Efficacy and safety of thalidomide in patients with inflammatory manifestations of chronic granulomatous disease: a retrospective case series. J. Allergy Clin. Immunol. 132, 997–1000.e4 (2013).

    CAS  PubMed  Google Scholar 

  31. Dai, R. et al. Altered functions of neutrophils in two Chinese patients with severe congenital neutropenia type 4 caused by G6PC3 mutations. Front. Immunol. 12, 699743 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Sokol, H. et al. Thalidomide as a treatment for refractory CGD colitis. Am. J. Gastroenterol. 104, 1069 (2009).

    PubMed  Google Scholar 

  33. Kuloglu, Z. et al. An infant with severe refractory Crohn’s disease and homozygous MEFV mutation who dramatically responded to colchicine. Rheumatol. Int. 32, 783–785 (2012).

    PubMed  Google Scholar 

  34. Veenbergen, S. et al. IL-10 signaling in dendritic cells controls IL-1β-mediated IFNγ secretion by human CD4+ T cells: relevance to inflammatory bowel disease. Mucosal Immunol. 12, 1201–1211 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Egg, D. et al. Increased risk for malignancies in 131 affected CTLA4 mutation carriers. Front. Immunol. 9, 2012 (2018).

    PubMed  PubMed Central  Google Scholar 

  36. Uhlig, H. H. Mendelian diseases and inflammatory bowel disease – data mining for genetic risk and disease-associated confounders. Inflamm. Bowel Dis. 24, 467–470 (2018).

    PubMed  Google Scholar 

  37. Schmitt, M. M. et al. Mycophenolate-induced colitis in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy patients. JPGN Rep. 2, e131 (2021).

    PubMed  PubMed Central  Google Scholar 

  38. Naviglio, S. et al. Severe inflammatory bowel disease associated with congenital alteration of transforming growth factor beta signaling. J. Crohns Colitis 8, 770–774 (2014).

    PubMed  Google Scholar 

  39. van Andel, M. M. et al. Long-term clinical outcomes of losartan in patients with Marfan syndrome: follow-up of the multicentre randomized controlled COMPARE trial. Eur. Heart J. 41, 4181–4187 (2020).

    PubMed  PubMed Central  Google Scholar 

  40. Asgharzadeh, F. et al. The beneficial effect of combination therapy with sulfasalazine and valsartan in the treatment of ulcerative colitis. EXCLI J. 20, 236–247 (2021).

    PubMed  PubMed Central  Google Scholar 

  41. Wengrower, D. et al. Losartan reduces trinitrobenzene sulphonic acid-induced colorectal fibrosis in rats. Can. J. Gastroenterol. 26, 33–39 (2012).

    PubMed  PubMed Central  Google Scholar 

  42. Liu, T. J., Shi, Y. Y., Wang, E. B., Zhu, T. & Zhao, Q. AT1R blocker losartan attenuates intestinal epithelial cell apoptosis in a mouse model of Crohn’s disease. Mol. Med. Rep. 13, 1156–1162 (2016).

    CAS  PubMed  Google Scholar 

  43. Bolton, C. et al. Remission of inflammatory bowel disease in glucose-6-phosphatase 3 deficiency by allogeneic haematopoietic stem cell transplantation. J. Crohns Colitis 14, 142–147 (2020).

    PubMed  Google Scholar 

  44. Dieckgraefe, B. K., Korzenik, J. R., Husain, A. & Dieruf, L. Association of glycogen storage disease 1b and Crohn disease: results of a North American survey. Eur. J. Pediatr. 161, S88–S92 (2002).

    PubMed  Google Scholar 

  45. Veiga-da-Cunha, M. et al. Failure to eliminate a phosphorylated glucose analog leads to neutropenia in patients with G6PT and G6PC3 deficiency. Proc. Natl Acad. Sci. USA 116, 1241–1250 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Wortmann, S. B. et al. Treating neutropenia and neutrophil dysfunction in glycogen storage disease type Ib with an SGLT2 inhibitor. Blood 136, 1033–1043 (2020).

    PubMed  PubMed Central  Google Scholar 

  47. Grunert, S. C. et al. Improved inflammatory bowel disease, wound healing and normal oxidative burst under treatment with empagliflozin in glycogen storage disease type Ib. Orphanet J. Rare Dis. 15, 218 (2020).

    PubMed  PubMed Central  Google Scholar 

  48. Williams, I. et al. Anti-TNF therapy for inflammatory bowel disease in patients with neurodegenerative Niemann–Pick disease type C. Wellcome Open Res. 7, 11 (2022).

    PubMed  PubMed Central  Google Scholar 

  49. O’Brien, K. J. et al. Inflammatory bowel disease in HermanskyPudlak syndrome: a retrospective single-centre cohort study. J. Intern. Med. 290, 129–140 (2021).

    PubMed  Google Scholar 

  50. Mao, L. et al. Loss-of-function CARD8 mutation causes NLRP3 inflammasome activation and Crohn’s disease. J. Clin. Invest. 128, 1793–1806 (2018).

    PubMed  PubMed Central  Google Scholar 

  51. Levy, M. et al. Severe early-onset colitis revealing mevalonate kinase deficiency. Pediatrics 132, e779–e783 (2013).

    PubMed  Google Scholar 

  52. Shouval, D. S. et al. Interleukin 1β mediates intestinal inflammation in mice and patients with interleukin 10 receptor deficiency. Gastroenterology 151, 1100–1104 (2016).

    CAS  PubMed  Google Scholar 

  53. Li, J., Shouval, D. S., Doty, A. L., Snapper, S. B. & Glover, S. C. Increased mucosal IL-22 production of an IL-10RA mutation patient following anakin treatment suggests further mechanism for mucosal healing. J. Clin. Immunol. 37, 104–107 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Canna, S. W. et al. Life-threatening NLRC4-associated hyperinflammation successfully treated with IL-18 inhibition. J. Allergy Clin. Immunol. 139, 1698–1701 (2017).

    CAS  PubMed  Google Scholar 

  55. Wada, T. et al. Sustained elevation of serum interleukin-18 and its association with hemophagocytic lymphohistiocytosis in XIAP deficiency. Cytokine 65, 74–78 (2014).

    CAS  PubMed  Google Scholar 

  56. Lo, B. et al. Patients with LRBA deficiency show CTLA4 loss and immune dysregulation responsive to abatacept therapy. Science 349, 436–440 (2015).

    CAS  PubMed  Google Scholar 

  57. Tesch, V. K. et al. Long-term outcome of LRBA deficiency in 76 patients after various treatment modalities as evaluated by the immune deficiency and dysregulation activity (IDDA) score. J. Allergy Clin. Immunol. 145, 1452–1463 (2020).

    CAS  PubMed  Google Scholar 

  58. Ozen, A. et al. Broadly effective metabolic and immune recovery with C5 inhibition in CHAPLE disease. Nat. Immunol. 22, 128–139 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Danese, S., Solitano, V., Jairath, V. & Peyrin-Biroulet, L. The future of drug development for inflammatory bowel disease: the need to ACT (advanced combination treatment). Gut 71, 2380–2387 (2022).

    CAS  PubMed  Google Scholar 

  60. Hudson, A. A., Almeida, P. & Huynh, H. Dual biologic therapy in a patient with Niemann–Pick type C and Crohn disease: a case report and literature review. JPGN Rep. 3, e225 (2022).

    PubMed  PubMed Central  Google Scholar 

  61. Goenka, A. et al. Neutrophil dysfunction triggers inflammatory bowel disease in G6PC3 deficiency. J. Leukoc. Biol. 109, 1147–1154 (2021).

    CAS  PubMed  Google Scholar 

  62. Barmettler, S. et al. Gastrointestinal manifestations in X-linked agammaglobulinemia. J. Clin. Immunol. 37, 287–294 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Aydemir, S. et al. Inflammatory bowel disease and Guillain Barre syndrome in FCHO1 deficiency. J. Clin. Immunol. 41, 1406–1410 (2021).

    PubMed  Google Scholar 

  64. Marsh, R. A. et al. Chronic granulomatous disease-associated IBD resolves and does not adversely impact survival following allogeneic HCT. J. Clin. Immunol. 39, 653–667 (2019).

    PubMed  PubMed Central  Google Scholar 

  65. Peng, K. et al. Umbilical cord blood transplantation corrects very early-onset inflammatory bowel disease in Chinese patients with IL10RA-associated immune deficiency. Inflamm. Bowel Dis. 24, 1416–1427 (2018).

    PubMed  Google Scholar 

  66. Ashton, J. J., Gavin, J. & Beattie, R. M. Exclusive enteral nutrition in Crohn’s disease: evidence and practicalities. Clin. Nutr. 38, 80–89 (2019).

    PubMed  Google Scholar 

  67. Murugan, D. et al. Very early onset inflammatory bowel disease associated with aberrant trafficking of IL-10R1 and cure by T cell replete haploidentical bone marrow transplantation. J. Clin. Immunol. 34, 331–339 (2014).

    CAS  PubMed  Google Scholar 

  68. Freudenberg, F. et al. Therapeutic strategy in p47-phox deficient chronic granulomatous disease presenting as inflammatory bowel disease. J. Allergy Clin. Immunol. 125, 943–946.e1 (2010).

    CAS  PubMed  Google Scholar 

  69. Norsa, L. et al. Inflammatory bowel disease in patients with congenital chloride diarrhoea. J. Crohns Colitis 15, 1679–1685 (2021).

    PubMed  Google Scholar 

  70. Janecke, A. R. et al. Reduced sodium/proton exchanger NHE3 activity causes congenital sodium diarrhea. Hum. Mol. Genet. 24, 6614–6623 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Fiskerstrand, T. et al. Familial diarrhea syndrome caused by an activating GUCY2C mutation. N. Engl. J. Med. 366, 1586–1595 (2012).

    CAS  PubMed  Google Scholar 

  72. Sokol, H. et al. Intestinal dysbiosis in inflammatory bowel disease associated with primary immunodeficiency. J. Allergy Clin. Immunol. 143, 775–778.e6 (2019).

    PubMed  Google Scholar 

  73. Xue, A. J. et al. Intestinal dysbiosis in pediatric Crohn’s disease patients with IL10RA mutations. World J. Gastroenterol. 26, 3098–3109 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Wang, L. et al. Gain-of-function variants in SYK cause immune dysregulation and systemic inflammation in humans and mice. Nat. Genet. 53, 500–510 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Ono, S. et al. Hematopoietic cell transplantation rescues inflammatory bowel disease and dysbiosis of gut microbiota in XIAP deficiency. J. Allergy Clin. Immunol. Pract. 9, 3767–3780 (2021).

    CAS  PubMed  Google Scholar 

  76. Huang, Z. et al. Mutations in interleukin-10 receptor and clinical phenotypes in patients with very early onset inflammatory bowel disease: a Chinese VEO-IBD Collaboration Group survey. Inflamm. Bowel Dis. 23, 578–590 (2017).

    PubMed  Google Scholar 

  77. Quaranta, M. et al. Consequences of identifying XIAP deficiency in an adult patient with inflammatory bowel disease. Gastroenterology 155, 231–234 (2018).

    PubMed  Google Scholar 

  78. Arnold, D. E. et al. Reduced-intensity/reduced-toxicity conditioning approaches are tolerated in XIAP deficiency but patients fare poorly with acute GVHD. J. Clin. Immunol. 42, 36–45 (2022).

    PubMed  Google Scholar 

  79. Ruemmele, F. M. et al. Outcome measures for clinical trials in paediatric IBD: an evidence-based, expert-driven practical statement paper of the paediatric ECCO committee. Gut 64, 438–446 (2015).

    PubMed  Google Scholar 

  80. Turner, D. et al. STRIDE-II: an update on the selecting therapeutic targets in inflammatory bowel disease (STRIDE) initiative of the International Organization for the Study of IBD (IOIBD): determining therapeutic goals for treat-to-target strategies in IBD. Gastroenterology 160, 1570–1583 (2021).

    CAS  PubMed  Google Scholar 

  81. Opréa, A. C.-F. et al. Therapeutic approach of very early-onset inflammatory bowel disease in a Loeys–Dietz syndrome child. JPGN Rep. 3, e139 (2022).

    PubMed  Google Scholar 

  82. Attauabi, M. et al. Comparative onset of effect of biologics and small molecules in moderate-to-severe ulcerative colitis: a systematic review and network meta-analysis. EClinicalMedicine 57, 101866 (2023).

    PubMed  PubMed Central  Google Scholar 

  83. Dike, C. R., Bernat, J., Bishop, W. & DeGeeter, C. Niemann–Pick disease type C presenting as very early onset inflammatory bowel disease. BMJ Case Rep. 12, e229780 (2019).

    PubMed  PubMed Central  Google Scholar 

  84. Uzel, G. et al. Complications of tumor necrosis factor-α blockade in chronic granulomatous disease-related colitis. Clin. Infect. Dis. 51, 1429–1434 (2010).

    PubMed  PubMed Central  Google Scholar 

  85. Conrad, A. et al. Infections in patients with chronic granulomatous disease treated with tumor necrosis factor alpha blockers for inflammatory complications. J. Clin. Immunol. 41, 185–193 (2021).

    CAS  PubMed  Google Scholar 

  86. Braun, C. J. et al. Gene therapy for Wiskott-Aldrich syndrome – long-term efficacy and genotoxicity. Sci. Transl Med. 6, 227–233 (2014).

    Google Scholar 

  87. Vogelin, M. et al. The impact of azathioprine-associated lymphopenia on the onset of opportunistic infections in patients with inflammatory bowel disease. PLoS ONE 11, e0155218 (2016).

    PubMed  PubMed Central  Google Scholar 

  88. Nori, M. ‘Negative’ clinical trials in rare diseases and beyond: reclassification and potential solutions. Future Rare Dis. 1, 10.2217/frd-2020-0005 (2021).

  89. de Luca, A. et al. IL-1 receptor blockade restores autophagy and reduces inflammation in chronic granulomatous disease in mice and in humans. Proc. Natl Acad. Sci. USA 111, 3526–3531 (2014).

    PubMed  PubMed Central  Google Scholar 

  90. Hahn, K. J. et al. Treatment with anakinra, a recombinant IL-1 receptor antagonist, unlikely to induce lasting remission in patients with CGD colitis. Am. J. Gastroenterol. 110, 938–939 (2015).

    CAS  PubMed  Google Scholar 

  91. Aschenbrenner, D. et al. Pathogenic interleukin-10 receptor alpha variants in humans – balancing natural selection and clinical implications. J. Clin. Immunol. 43, 495–511 (2023).

    CAS  PubMed  Google Scholar 

  92. Marsh, R. A. et al. Allogeneic hematopoietic cell transplantation for XIAP deficiency: an international survey reveals poor outcomes. Blood 121, 877–883 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Kuehn, H. S. et al. Immune dysregulation in human subjects with heterozygous germline mutations in CTLA4. Science 345, 1623–1627 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Schubert, D. et al. Autosomal dominant immune dysregulation syndrome in humans with CTLA4 mutations. Nat. Med. 20, 1410–1416 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Gagne, J. J., Thompson, L., O’Keefe, K. & Kesselheim, A. S. Innovative research methods for studying treatments for rare diseases: methodological review. BMJ 349, g6802 (2014).

    PubMed  PubMed Central  Google Scholar 

  96. Whicher, D., Philbin, S. & Aronson, N. An overview of the impact of rare disease characteristics on research methodology. Orphanet J. Rare Dis. 13, 14 (2018).

    PubMed  PubMed Central  Google Scholar 

  97. Santoro, M. et al. Rare disease registries classification and characterization: a data mining approach. Public Health Genomics 18, 113–122 (2015).

    PubMed  Google Scholar 

  98. European Commission. Set of common data elements for rare diseases registration. EU RD Platform https://eu-rd-platform.jrc.ec.europa.eu/set-of-common-data-elements_en (2023).

  99. Salter, C. G. et al. Biallelic PI4KA variants cause neurological, intestinal and immunological disease. Brain 144, 3597–3610 (2021).

    PubMed  PubMed Central  Google Scholar 

  100. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research (US Department of Health and Human Services, 1979).

  101. Borysowski, J., Ehni, H. J. & Gorski, A. Ethics review in compassionate use. BMC Med. 15, 136 (2017).

    PubMed  PubMed Central  Google Scholar 

  102. Vohra, S. et al. CONSORT extension for reporting N-of-1 trials (CENT) 2015 Statement. J. Clin. Epideminol 76, 9–17 (2016).

    Google Scholar 

  103. Turner, D. et al. Designing clinical trials in paediatric inflammatory bowel diseases: a PIBDnet commentary. Gut 69, 32–41 (2020).

    PubMed  Google Scholar 

  104. Faingelernt, Y. et al. Correlation between the Nancy Histopathology Index and markers of disease activity in pediatric ulcerative colitis. J. Pediatr. Gastroenterol. Nutr. 76, 782–785 (2023).

    CAS  PubMed  Google Scholar 

  105. Ricciuto, A. et al. Prospective evaluation of endoscopic and histologic indices in pediatric ulcerative colitis using centralized review. Am. J. Gastroenterol. 116, 2052–2059 (2021).

    PubMed  Google Scholar 

  106. Walsh, A. J., Bryant, R. V. & Travis, S. P. Current best practice for disease activity assessment in IBD. Nat. Rev. Gastroenterol. Hepatol. 13, 567–579 (2016).

    CAS  PubMed  Google Scholar 

  107. Tran, F. et al. Patient reported outcomes in chronic inflammatory diseases: current state, limitations and perspectives. Front. Immunol. 12, 614653 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  108. Grassly, N. C. et al. The effect of azithromycin on the immunogenicity of oral poliovirus vaccine: a double-blind randomised placebo-controlled trial in seronegative Indian infants. Lancet Infect. Dis. 16, 905–914 (2016).

    CAS  PubMed  Google Scholar 

  109. Subbiah, V. The next generation of evidence-based medicine. Nat. Med. 29, 49–58 (2023).

    CAS  PubMed  Google Scholar 

  110. Raine, T. et al. Establishment of a validated central reading system for ileocolonoscopy in an academic setting. Gut 71, 661–664 (2022).

    PubMed  Google Scholar 

  111. Byrne, M. F. et al. Application of deep learning models to improve ulcerative colitis endoscopic disease activity scoring under multiple scoring systems. J. Crohns Colitis 19, 463–471 (2023).

    Google Scholar 

  112. Sutton, R. T., Zai Ane, O. R., Goebel, R. & Baumgart, D. C. Artificial intelligence enabled automated diagnosis and grading of ulcerative colitis endoscopy images. Sci. Rep. 12, 2748 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  113. Crowley, E., Griffiths, A. M. & Jairath, V. pIBD Clinical Trials Outcome Group Heterogeneity in efficacy and safety endpoints for pediatric clinical trials in inflammatory bowel disease: a need for harmonization. Gastroenterology 163, 1137–1144 (2022).

    PubMed  Google Scholar 

  114. Cavounidis, A. et al. Hermansky-Pudlak syndrome type 1 causes impaired anti-microbial immunity and inflammation due to dysregulated immunometabolism. Mucosal Immunol. 15, 1431–1446 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  115. Friedrich, M. et al. IL-1-driven stromal-neutrophil interactions define a subset of patients with inflammatory bowel disease that does not respond to therapies. Nat. Med. 27, 1970–1981 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  116. Huang, C. et al. Genetic risk for inflammatory bowel disease is a determinant of Crohn’s disease development in chronic granulomatous disease. Inflamm. Bowel Dis. 22, 2794–2801 (2016).

    PubMed  Google Scholar 

  117. Jardine, S. et al. Drug screen identifies leflunomide for treatment of inflammatory bowel disease caused by TTC7A deficiency. Gastroenterology 158, 1000–1015 (2020).

    CAS  PubMed  Google Scholar 

  118. Ip, W. K. E., Hoshi, N., Shouval, D. S., Snapper, S. & Medzhitov, R. Anti-inflammatory effect of IL-10 mediated by metabolic reprogramming of macrophages. Science 356, 513–519 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  119. Omarjee, O. et al. LACC1 deficiency links juvenile arthritis with autophagy and metabolism in macrophages. J. Exp. Med. 218, e20201006 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  120. Coulter, T. I. & Cant, A. J. The treatment of activated PI3Kδ syndrome. Front. Immunol. 9, 2043 (2018).

    PubMed  PubMed Central  Google Scholar 

  121. Minshawi, F. et al. The generation of an engineered interleukin-10 protein with improved stability and biological function. Front. Immunol. 11, 1794 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  122. Zurita-Turk, M. et al. Attenuation of intestinal inflammation in IL-10 deficient mice by a plasmid carrying Lactococcus lactis strain. BMC Biotechnol. 20, 38 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  123. Braat, H. et al. A phase I trial with transgenic bacteria expressing interleukin-10 in Crohn’s disease. Clin. Gastroenterol. Hepatol. 4, 754–759 (2006).

    CAS  PubMed  Google Scholar 

  124. Bruijnen, S. T. G. et al. F8-IL10: a new potential antirheumatic drug evaluated by a PET-guided translational approach. Mol. Pharm. 16, 273–281 (2019).

    CAS  PubMed  Google Scholar 

  125. Watanabe, S. et al. Transplantation of intestinal organoids into a mouse model of colitis. Nat. Protoc. 17, 649–671 (2022).

    CAS  PubMed  Google Scholar 

  126. Ko, J. Z., Johnson, S. & Dave, M. Efficacy and safety of mesenchymal stem/stromal cell therapy for inflammatory bowel diseases: an up-to-date systematic review. Biomolecules 11, 82 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  127. Sweeney, C. L. et al. Correction of X-CGD patient HSPCs by targeted CYBB cDNA insertion using CRISPR/Cas9 with 53BP1 inhibition for enhanced homology-directed repair. Gene Ther. 28, 373–390 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  128. Madsen, K. L. et al. Antibiotic therapy attenuates colitis in interleukin 10 gene-deficient mice. Gastroenterology 118, 1094–1105 (2000).

    CAS  PubMed  Google Scholar 

  129. Li, S. et al. Intermittent antibiotic treatment accelerated the development of colitis in IL-10 knockout mice. Biomed. Pharmacother. 146, 112486 (2021).

    PubMed  Google Scholar 

  130. Vetizou, M. et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science 350, 1079–1084 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  131. de la Morena-Barrio, M. E. et al. MPI-CDG with transient hypoglycosylation and antithrombin deficiency. Haematologica 104, e79–e82 (2019).

    PubMed  PubMed Central  Google Scholar 

  132. Yang, L. et al. Phenotype, genotype, treatment, and survival outcomes in patients with X-linked inhibitor of apoptosis deficiency. J. Allergy Clin. Immunol. 150, 456–466 (2022).

    CAS  PubMed  Google Scholar 

  133. Čechová, A. et al. Consensus guideline for the diagnosis and management of mannose phosphate isomerase-congenital disorder of glycosylation. J. Inherit. Metab. Dis. 43, 671–693 (2020).

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors thank patients and their families who have shared their experiences and contributed to research. The authors thank the Crohn’s in Childhood Research Association (CICRA), the XLP Research Trust and the Chronic Granulomatous Disorder Society (CGD Society) for their supportive feedback. A.M.M., H.H.U., C.K., D.K., S.B.S., J.C. and D.P.B.McG. are supported by the Leona M. and Harry B. Helmsley Charitable Trust. S.P.T. and H.H.U. are supported by the NIHR Oxford Biomedical Research Centre, University of Oxford; K.J. and C.B. are supported by the GOSH NIHR Biomedical Research Centre, London. B.G. is supported by RESIST-EXC 2155-Project (ID 390874280) and the BMBF (GAIN 01GM1910A). S.B.S is funded by the Wolpow Family Chair in IBD Treatment and Research, the Egan Family Foundation Chair, the Children’s Rare Disease Cohort Initiative, and NIDDK RC2DK122532. A.M.M. is funded by the Canada Research Chair (Tier 1) in Paediatric IBD, CIHR Foundation Grant, and NIDDK NIH (RC2DK118640 and RC2DK122532).

Author information

Authors and Affiliations

  1. Translational Gastroenterology Unit, University of Oxford, Oxford, UK

    Holm H. Uhlig & Simon P. Travis

  2. Department of Paediatrics, University of Oxford, Oxford, UK

    Holm H. Uhlig

  3. Biomedical Research Centre, University of Oxford, Oxford, UK

    Holm H. Uhlig & Simon P. Travis

  4. UCL Great Ormond Street Institute of Child Health, London, UK

    Claire Booth

  5. Department of Paediatric Immunology and Gene Therapy, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK

    Claire Booth

  6. Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Judy Cho

  7. Department of Paediatric Gastroenterology, Susan and Leonard Feinstein IBD Clinical Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Marla Dubinsky

  8. SickKids Inflammatory Bowel Disease Centre and Cell Biology Program, Research Institute, Toronto, Canada

    Anne M. Griffiths & Aleixo M. Muise

  9. Division of Gastroenterology, Hepatology, and Nutrition, Department of Paediatrics, University of Toronto, Toronto, Canada

    Anne M. Griffiths & Aleixo M. Muise

  10. Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center, Faculty of Medicine, Albert Ludwig University of Freiburg, Freiburg, Germany

    Bodo Grimbacher

  11. Department of Rheumatology and Clinical Immunology, Medical Center, Faculty of Medicine, Albert Ludwig University of Freiburg, Freiburg, Germany

    Bodo Grimbacher

  12. Institute of Immunology and Transplantation, Royal Free Hospital, University College London, London, UK

    Bodo Grimbacher

  13. Primary Immunodeficiency Group, Newcastle University Translational and Clinical Research Institute, Newcastle upon Tyne, UK

    Sophie Hambleton

  14. Department of Gastroenterology, National Children’s Medical Center, Children’s Hospital of Fudan University, Shanghai, China

    Ying Huang

  15. Paediatric Gastroenterology, Great Ormond Street Hospital, London, UK

    Kelsey Jones

  16. Kennedy Institute, University of Oxford, Oxford, UK

    Kelsey Jones & Simon P. Travis

  17. Gastroenterology Department, Evelina London Children’s Hospital, London, UK

    Jochen Kammermeier

  18. Department of Child Health and Development, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan

    Hirokazu Kanegane

  19. Dr. von Hauner Children’s Hospital, Department of Paediatrics, University Hospital, LMU Munich, Munich, Germany

    Sibylle Koletzko, Daniel Kotlarz & Christoph Klein

  20. Department of Paediatrics, Gastroenterology and Nutrition, School of Medicine Collegium Medicum University of Warmia and Mazury, Olsztyn, Poland

    Sibylle Koletzko

  21. German Center for Child and Adolescent Health, Munich, Germany

    Daniel Kotlarz & Christoph Klein

  22. Institute of Translational Genomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany

    Daniel Kotlarz

  23. Molecular Development of the Immune System Section, Laboratory of Immune System Biology, and Clinical Genomics Program, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA

    Michael J. Lenardo

  24. Research Branch, Sidra Medicine, Doha, Qatar

    Bernice Lo

  25. College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar

    Bernice Lo

  26. F. Widjaja Foundation, Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA

    Dermot P. B. McGovern

  27. Marmara University Division of Allergy and Immunology, Istanbul, Turkey

    Ahmet Özen

  28. Department of Paediatric Gastroenterology, Erasmus University Medical Center Sophia Children’s Hospital, Rotterdam, Netherlands

    Lissy de Ridder

  29. Université Paris Cité, APHP, Hôpital Necker Enfants Malades, Service de Gastroentérologie pédiatrique, Paris, France

    Frank Ruemmele

  30. Institute of Gastroenterology, Nutrition and Liver Diseases, Schneider Children’s Medical Center of Israel, Petah Tikva, Israel

    Dror S. Shouval

  31. Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Dror S. Shouval

  32. Division of Gastroenterology and Nutrition, Boston Children’s Hospital, Boston, MA, USA

    Scott B. Snapper

  33. Department of Paediatrics and Department of Medicine, Harvard Medical School, Boston, MA, USA

    Scott B. Snapper

  34. Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel

    Dan Turner

  35. Child Life and Health, Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK

    David C. Wilson

  36. Department of Paediatric Gastroenterology, The Royal Hospital for Children, and Young People, Edinburgh, UK

    David C. Wilson

  37. Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada

    Aleixo M. Muise

  38. Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada

    Aleixo M. Muise

  39. Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada

    Aleixo M. Muise

Authors
  1. Holm H. Uhlig
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Claire Booth
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Judy Cho
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Marla Dubinsky
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Anne M. Griffiths
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Bodo Grimbacher
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sophie Hambleton
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ying Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Kelsey Jones
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jochen Kammermeier
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Hirokazu Kanegane
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Sibylle Koletzko
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Daniel Kotlarz
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Christoph Klein
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Michael J. Lenardo
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Bernice Lo
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Dermot P. B. McGovern
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Ahmet Özen
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Lissy de Ridder
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Frank Ruemmele
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Dror S. Shouval
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Scott B. Snapper
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Simon P. Travis
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. Dan Turner
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. David C. Wilson
    View author publications

    You can also search for this author in PubMed Google Scholar

  26. Aleixo M. Muise
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

H.H.U., S.P.T. and A.M.M. researched data for the article, made a substantial contribution to discussion of content, wrote the article, and reviewed/edited the manuscript before submission. C.B., J.C., M.D., B.G., J.K., D.K., C.K., B.L., D.P.B.McG., F.R., D.S.S., S.B.S. and D.C.W. made a substantial contribution to discussion of content, and reviewed/edited the manuscript before submission. A.M.G., S.H., K.J., M.J.L., L.d.R. and D.T. made a substantial contribution to discussion of content, wrote the article, and reviewed/edited the manuscript before submission. Y.H., H.K., S.K. and A.Ö. researched data for the article, made a substantial contribution to discussion of content, and reviewed/edited the manuscript before submission.

Corresponding author

Correspondence to Holm H. Uhlig.

Ethics declarations

Competing interests

This Expert Recommendation was not influenced or supported by any commercial entity outside the academic institutions. H.H.U. received research support or consultancy fees from Janssen, Eli Lilly, UCB Pharma, BMS/Celgene, MiroBio, OMass and Mestag. J.C. reports that Sema4 performed sequencing of BioMe biobank, RGC (Regeneron Genetics Center) supported MRGPRX2 studies, ImmuneID supported biomarker development, Renalytix supported biomarker development. M.D. received a consulting fees from AbbVie Inc., Arena Pharmaceuticals, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Celgene Corporation, Eli Lilly and Company, F. Hoffmann-La Roche Ltd., Genentech Inc, Gilead, Janssen Global Services LLB, Pfizer Inc., Prometheus Biosciences, Takeda Pharmaceuticals USA Inc. and UCB SA; performed contracted research for AbbVie Inc., Janssen Global Services LLC, Pfizer Inc. and Prometheus Biosciences; has an ownership interest in Trellus Health Inc., and has received a licensing fee from Takeda Pharmaceuticals USA Inc. A.M.G. has acted as a consultant or advisory board member for Abbvie, Amgen, Bristol-Myers Squibb, Lilly, Merck, Janssen, Pfizer and Takeda; has received speaker fees from Abbvie and Janssen; and has received investigator-initiated research support from Abbvie. B.G. receives funding for his research from the following third parties: Deutsche Forschungsgemeinschaft (DFG), the E-rare program of the EU, managed by the DFG, the Netzwerke Seltener Erkrankungen of the German Ministry of Education and Research (BMBF), Merck KGaA, Takeda Pharma Vertrieb GmbH & Co. KG, Bristol-Myers Squibb GmbH & Co. KGaA, Novartis Pharma AG, and CSL Behring GmbH. During the last 3 years B.G. was an adviser to the following companies: Bristol-Myers Squibb, Adivo Associates Germany, Pharming Group NV, Epimune GmbH, GigaGen Inc., Atheneum Partners GmbH, UCB Pharma SA and Roche Pharma AG. S.H. reports consultancy fees from Takeda, Videregen and Pharming; and honoraria from Biotest and UCB. K.J. received speaker fees from Celltrion. S.K. reports grants given to the institution from Mead Johnson, Nestec Nutrition and BioGaia, and personal fees from Nestlé, Danone, Mead Johnson, Biocodex, Shire, Abbvie, Vifor, Pharmacosmos, Celgene. ThermoFisher, Janssen and Pfizer outside the submitted work. D.K. reports a sponsor research agreement with Celsius Therapeutics Inc., D.P.B.McG. is a consultant and holds stock in Prometheus Biosciences, and has consulted for Takeda, Gilead, Pfizer and Prometheus Laboratories. A.Ö. acts as a steering committee member for a clinical trial sponsored by Regeneron Pharmaceuticals and received research funds from this company, and also has a pending patent on C5 inhibitor treatment of CHAPLE. L.d.R. reports collaboration (including involvement in industry-sponsored studies, an investigator-initiated study and consultancy) with Abbvie, Lilly, Takeda, Janssen and Pfizer. F.R. served as scientific board member or has received speaker fees from Johnson & Johnson, Centocor, AbbVie, Nestlé Nutrition Institute, Nestlé Health Science, Takeda, Celgene, Biogen and Bristol-Meyers Squibb. D.S.S. reports a research grant from Takeda, and consulting and lecturing fees from Jansen, AbbVie and Takeda. S.B.S. is supported by grants or in-kind contributions from Pfizer, Novartis, Janssen, Merck and Regeneron, is on the scientific advisory boards of Pfizer, Janssen, IFM Therapeutics, Lycera, Inc., Celgene, Lilly, Pandion Therapeutics and Applied Molecular Transport, and has consulted for Amgen and Hoffman La-Roche. S.P.T. was employed by the University of Oxford (and, until 31 March 2022, Oxford University Hospitals NHS Trust), has received graah support from AbbVie, Buhlmann, Celgene, ECCO, Helmsley Trust, IOIBD, Janssen, Lilly, Pfizer, Takeda, UCB, UKIERI, Vifor and Norman Collisson Foundation, consulting fees from Abacus, AbbVie, Actial, ai4gi, Alcimed, Allergan, Amgen, Aptel, Arena, Asahi, Aspen, Astellas, Atlantic, AstraZeneca, Barco, Biocare, Biogen, BLPharma, Boehringer Ingelheim, Bristol-Meyers Squibb, Buhlmann, Calcico, Celgene, Cellerix, Cerimon, ChemoCentryx, Chiesi, CisBio, ComCast, Coronado, Cosmo, Ducentis, Dynavax, Elan, Enterome, Equillium, Falk, Ferring, FPRT Bio, Galapagos, Genentech/Roche, Genzyme, Gilead, Glenmark, Grunenthal, GSK, GW Pharmaceuticals, Immunocore, Immunometabolism, Indigo, Janssen, Lexicon, Lilly, Medarex, Medtrix, Merck, Merrimack, Mestag. Millenium, Neovacs, Novartis, Novo Nordisk, NPS-Nycomed, Ocera, Optima, Origin, Otsuka, Palau, Pentax, Pfizer, Pharmaventure, Phesi, Phillips, P&G, Pronota, Protagonist, Proximagen, Resolute, Robarts, Sandoz, Santarus, Satisfai, Sensyne Health, Shire, SigmoidPharma, Sorriso, Souffinez, Syndermix, Synthon, Takeda, Theravance, Tigenix, Tillotts, Topivert, Trino Therapeutics with Wellcome Trust, TxCell, UCB Pharma, Vertex, VHsquared, Vifor, Warner Chilcott and Zeria, and speaker fees from AbbVie, Amgen, Biogen, Falk, Ferring, Janssen, Pfizer, Shire, Takeda and UCB, but has no stocks or share options. D.T. has received consultation fees, a research grant, royalties or honoraria from Janssen, Pfizer, Hospital for Sick Children, Ferring, Abbvie, Takeda, Atlantic Health, Shire, Celgene, Lilly, Roche, ThermoFisher, Bristol-Meyers-Squibb and SorrisoPharma. D.C.W. has received consultancy fees, speaker fees and/or travel support from Abbvie, Nestlé Health Sciences and Roche. The other authors declare no competing interests.

Peer review

Peer review information

Nature Reviews Gastroenterology & Hepatology thanks Robert Beattie, Judith Kelsen and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Related links

ClinicalTrials.gov database: https://clinicaltrials.gov/

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Uhlig, H.H., Booth, C., Cho, J. et al. Precision medicine in monogenic inflammatory bowel disease: proposed mIBD REPORT standards. Nat Rev Gastroenterol Hepatol 20, 810–828 (2023). https://doi.org/10.1038/s41575-023-00838-4

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41575-023-00838-4

Search

Advanced search

Quick links

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research