{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T23:33:23Z","timestamp":1790379203231,"version":"4.1.0"},"reference-count":22,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2019,12,24]],"date-time":"2019-12-24T00:00:00Z","timestamp":1577145600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"(Agence Nationale de la Recherche, Paris, France","award":["ANR-2011 program (RPIB  021 01),"],"award-info":[{"award-number":["ANR-2011 program (RPIB  021 01),"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Despite the development of novel therapies, inflammatory bowel diseases remain an innovative treatment challenge. Helminth therapy is a new promising approach, and a key issue is the identification of helminth-derived anti-inflammatory mediators. P28 glutathione-S-transferase (P28GST), a protein derived from schistosomes, a trematode parasitic helminth, was shown to reduce intestinal inflammation in experimental colitis by down-regulating the Th1\/Th17 response. In this multicenter, open-label, pilot Phase 2a study, we evaluated the safety of P28GST administered to patients with mild Crohn\u2019s disease (CD). We enrolled 10 patients with a baseline Crohn\u2019s disease activity index (CDAI) value &lt;220. Eight patients received two to three subcutaneous injections of recombinant P28GST with adjuvant. This three-month treatment was followed by a nine-month monitoring period. The primary endpoints were the monthly rate and seriousness of adverse events (AEs). Secondary endpoints were clinical recurrence, assessed with the CDAI as well as the levels of immunologic and inflammatory blood and tissue markers. The most common AEs were local or regional events at the injection site and gastrointestinal disorders. At three months after the first injection, CDAI scores and blood calprotectin levels decreased in parallel. These results indicate that P28GST showed promise as a safe and new therapeutic option for treating CD.<\/jats:p>","DOI":"10.3390\/jcm9010041","type":"journal-article","created":{"date-parts":[[2019,12,24]],"date-time":"2019-12-24T10:28:43Z","timestamp":1577183323000},"page":"41","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Safety of P28GST, a Protein Derived from a Schistosome Helminth Parasite, in Patients with Crohn\u2019s Disease: A Pilot Study (ACROHNEM)"],"prefix":"10.3390","volume":"9","author":[{"given":"Monique","family":"Capron","sequence":"first","affiliation":[{"name":"U995\u2013LIRIC, Lille Inflammation Research International Center, Univ. Lille, Inserm, CHU Lille, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"B\u00e9ghin","sequence":"additional","affiliation":[{"name":"U995\u2013LIRIC, Lille Inflammation Research International Center, Univ. Lille, Inserm, CHU Lille, F-59000 Lille, France"},{"name":"CIC 1403, Centre d\u2019Investigation Clinique, Univ. Lille, Inserm, CHU Lille, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Leclercq","sequence":"additional","affiliation":[{"name":"Direction de la Recherche et de l\u2019Innovation, CHU Lille, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Labreuche","sequence":"additional","affiliation":[{"name":"EA 2694\u2013Sant\u00e9 Publique: \u00e9pid\u00e9miologie et Qualit\u00e9 des Soins, Univ. Lille, CHU Lille, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4918-2223","authenticated-orcid":false,"given":"Arnaud","family":"Dendooven","sequence":"additional","affiliation":[{"name":"U995\u2013LIRIC, Lille Inflammation Research International Center, Univ. Lille, Inserm, CHU Lille, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7752-3964","authenticated-orcid":false,"given":"Annie","family":"Standaert","sequence":"additional","affiliation":[{"name":"U995\u2013LIRIC, Lille Inflammation Research International Center, Univ. Lille, Inserm, CHU Lille, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Delbeke","sequence":"additional","affiliation":[{"name":"U995\u2013LIRIC, Lille Inflammation Research International Center, Univ. Lille, Inserm, CHU Lille, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8177-2461","authenticated-orcid":false,"given":"Adeline","family":"Porcherie","sequence":"additional","affiliation":[{"name":"Par\u2019Immune, Eurasante, F-59120 Loos lez Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Nachury","sequence":"additional","affiliation":[{"name":"U995\u2013LIRIC, Lille Inflammation Research International Center, Univ. Lille, Inserm, CHU Lille, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaud","family":"Boruchowicz","sequence":"additional","affiliation":[{"name":"Service des Maladies de l\u2019Appareil Digestif, Unit\u00e9 de Recherche Clinique, Centre Hospitalier de Valenciennes, F-59300 Valenciennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Louis","family":"Dupas","sequence":"additional","affiliation":[{"name":"Service d\u2019H\u00e9pato-Gastro-Ent\u00e9rologie, CHU Amiens Picardie, F-80054 Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathurin","family":"Fumery","sequence":"additional","affiliation":[{"name":"Service d\u2019H\u00e9pato-Gastro-Ent\u00e9rologie, CHU Amiens Picardie, F-80054 Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Paupard","sequence":"additional","affiliation":[{"name":"Service d\u2019H\u00e9pato-Gastro-Ent\u00e9rologie, Unit\u00e9 de Recherche Clinique, Centre Hospitalier de Dunkerque, F-59385 Dunkerque, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylviane","family":"Catteau","sequence":"additional","affiliation":[{"name":"Service d\u2019H\u00e9pato-Gastro-Ent\u00e9rologie, Unit\u00e9 de Recherche Clinique, Centre Hospitalier de Boulogne sur Mer, F-62200 Boulogne Sur Mer, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Deplanque","sequence":"additional","affiliation":[{"name":"CIC 1403, Centre d\u2019Investigation Clinique, Univ. Lille, Inserm, CHU Lille, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Frederic","family":"Colombel","sequence":"additional","affiliation":[{"name":"Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Desreumaux","sequence":"additional","affiliation":[{"name":"U995\u2013LIRIC, Lille Inflammation Research International Center, Univ. Lille, Inserm, CHU Lille, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1111\/apt.15072","article-title":"Long-term safety and tolerability of oral tofacitinib in patients with Crohn\u2019s disease: Results from a phase 2, open-label, 48-week extension study","volume":"49","author":"Higgins","year":"2019","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1016\/S1473-3099(14)70771-6","article-title":"Helminth therapy or elimination: Epidemiological, immunological, and clinical considerations","volume":"14","author":"Wammes","year":"2014","journal-title":"Lancet Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1038\/nri.2016.75","article-title":"Immunity by equilibrium","volume":"16","author":"Eberl","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"6009","DOI":"10.3748\/wjg.v23.i33.6009","article-title":"Helminths as an alternative therapy for intestinal diseases","volume":"23","author":"Sipahi","year":"2017","journal-title":"World J. Gastroenterol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1038\/mi.2015.62","article-title":"The schistosome glutathione S-transferase P28GST, a unique helminth protein, prevents intestinal inflammation in experimental colitis through a Th2-type response with mucosal eosinophils","volume":"9","author":"Driss","year":"2016","journal-title":"Mucosal. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Riveau, G., Deplanque, D., Remou\u00e9, F., Schacht, A.-M., Vodougnon, H., Capron, M., Thiry, M., Martial, J., Libersa, C., and Capron, A. (2012). Safety and Immunogenicity of rSh28GST Antigen in Humans: Phase 1 Randomized Clinical Study of a Vaccine Candidate against Urinary Schistosomiasis. PLoS Negl. Trop. Dis., 6.","DOI":"10.1371\/journal.pntd.0001704"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Riveau, G., Schacht, A.-M., Dompnier, J.-P., Deplanque, D., Seck, M., Waucquier, N., Senghor, S., Delcroix-Genete, D., Hermann, E., and Idris-Khodja, N. (2018). Safety and efficacy of the rSh28GST urinary schistosomiasis vaccine: A phase 3 randomized, controlled trial in Senegalese children. PLoS Negl. Trop. Dis., 12.","DOI":"10.1371\/journal.pntd.0006968"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Sarazin, A., Dendooven, A., Delbeke, M., Gatault, S., Pagny, A., Standaert, A., Rousseaux, C., Desreumaux, P., Dubuquoy, L., and Capron, M. (2018). Treatment with P28GST, a schistosome-derived enzyme, after acute colitis induction in mice: Decrease of intestinal inflammation associated with a down regulation of Th1\/Th17 responses. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0209681"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Folign\u00e9, B., Pl\u00e9, C., Tit\u00e9cat, M., Dendooven, A., Pagny, A., Daniel, C., Singer, E., Pottier, M., Bertin, B., and Neut, C. (2019). Contribution of the Gut Microbiota in P28GST-Mediated Anti-Inflammatory Effects: Experimental and Clinical Insights. Cells, 8.","DOI":"10.3390\/cells8060577"},{"key":"ref_10","first-page":"111","article-title":"Imputation of the unexpected or toxic effects of drugs. Actualization of the method used in France","volume":"40","author":"Evreux","year":"1985","journal-title":"Therapie"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/0016-5085(79)90384-6","article-title":"Rederived values of the eight coefficients of the Crohn\u2019s Disease Activity Index (CDAI)","volume":"77","author":"Best","year":"1979","journal-title":"Gastroenterology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"7387","DOI":"10.3748\/wjg.v23.i41.7387","article-title":"Fecal calprotectin measurement is a marker of short-term clinical outcome and presence of mucosal healing in patients with inflammatory bowel disease","volume":"23","author":"Kostas","year":"2017","journal-title":"World J. Gastroenterol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"29","DOI":"10.4137\/CGast.S20612","article-title":"Characterization of Serum Cytokine Profile in Predominantly Colonic Inflammatory Bowel Disease to Delineate Ulcerative and Crohn\u2019s Colitides","volume":"8","author":"Korolkova","year":"2015","journal-title":"Clin. Med. Insights Gastroenterol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1136\/gut.2004.041749","article-title":"Trichuris suis therapy in Crohn\u2019s disease","volume":"54","author":"Summers","year":"2005","journal-title":"Gut"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1053\/j.gastro.2005.01.005","article-title":"Trichuris suis therapy for active ulcerative colitis: A randomized controlled trial","volume":"128","author":"Summers","year":"2005","journal-title":"Gastroenterology"},{"key":"ref_16","first-page":"390","article-title":"A Randomised, Double-blind, Placebo-controlled Trial of Trichuris suis ova in Active Crohn\u2019s disease","volume":"11","author":"Fellermann","year":"2016","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"609","DOI":"10.14740\/jocmr3465w","article-title":"Ear Involvement in Inflammatory Bowel Disease: A Review of the Literature","volume":"10","author":"Fousekis","year":"2018","journal-title":"J. Clin. Med. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"459048","DOI":"10.1155\/2014\/459048","article-title":"Is Vestibular Neuritis an Immune Related Vestibular Neuropathy Inducing Vertigo?","volume":"2014","author":"Greco","year":"2014","journal-title":"J. Immunol. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4802","DOI":"10.3748\/wjg.v22.i20.4802","article-title":"Hydradenitis suppurativa and inflammatory bowel disease: An unusual, but existing association","volume":"22","author":"Principi","year":"2016","journal-title":"World J. Gastroenterol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.cgh.2015.04.180","article-title":"Features of Patients with Crohn\u2019s Disease and Hidradenitis Suppurativa","volume":"14","author":"Kamal","year":"2016","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"106","DOI":"10.4103\/2229-3485.71867","article-title":"Conducting feasibilities in clinical trials: An investment to ensure a good study","volume":"1","author":"Rajadhyaksha","year":"2010","journal-title":"Perspect. Clin. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e678","DOI":"10.1016\/j.crohns.2013.06.008","article-title":"Serum calprotectin as a biomarker for Crohn\u2019s disease","volume":"7","author":"Meuwis","year":"2013","journal-title":"J. Crohn\u2019s Colitis"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/9\/1\/41\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:45:08Z","timestamp":1760190308000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/9\/1\/41"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,24]]},"references-count":22,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,1]]}},"alternative-id":["jcm9010041"],"URL":"https:\/\/doi.org\/10.3390\/jcm9010041","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,24]]}}}