{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T22:28:02Z","timestamp":1789079282832,"version":"build-2803163510"},"reference-count":41,"publisher":"American Society for Clinical Investigation","issue":"12","license":[{"start":{"date-parts":[[2019,6,20]],"date-time":"2019-06-20T00:00:00Z","timestamp":1560988800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical Research Council","award":["G1100114\/1"],"award-info":[{"award-number":["G1100114\/1"]}]},{"name":"MOULTON CHARITABLE FOUNDATION","award":["RG67044"],"award-info":[{"award-number":["RG67044"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,6,20]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>The lymphocyte-depleting antibody alemtuzumab is a highly effective treatment for relapsing-remitting multiple sclerosis (RRMS); however, 50% of patients develop novel autoimmunity after treatment. Most at risk are individuals who reconstitute their T cell pool by proliferating residual cells, rather than producing new T cells in the thymus, raising the possibility that autoimmunity might be prevented by increasing thymopoiesis. Keratinocyte growth factor (palifermin) promotes thymopoiesis in nonhuman primates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      Following a dose tolerability substudy, individuals with RRMS (duration \u226410 years; expanded disability status scale \u22645.0, with \u22652 relapses in the previous 2 years) were randomized to placebo or 180 \u03bcg\/kg\/d palifermin, given for 3 days immediately before and after each cycle of alemtuzumab, with repeat doses at month 1 (M1) and M3. The interim primary endpoint was naive CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cell count at M6. Exploratory endpoints included number of recent thymic emigrants (RTEs) and signal joint T cell receptor excision circles\/ml (sjTRECs\/ml) of blood. The trial\u2019s primary endpoint was incidence of autoimmunity at M30.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      At M6, individuals receiving palifermin had fewer naive CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells (2.229 \u00d7 10\n                      <jats:sup>7<\/jats:sup>\n                      \/l vs. 7.733 \u00d7 10\n                      <jats:sup>7<\/jats:sup>\n                      \/l;\n                      <jats:italic>P<\/jats:italic>\n                      = 0.007), RTEs (16% vs. 34%), and sjTRECs\/ml (1100 vs. 3396), leading to protocol-defined termination of recruitment. No difference was observed in the rate of autoimmunity between the 2 groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>In contrast with animal studies, palifermin reduced thymopoiesis in our patients. These results offer a note of caution to those using palifermin to promote thymopoiesis in other settings, particularly in the oncology\/hematology setting, where alemtuzumab is often used as part of the conditioning regime.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>TRIAL REGISTRATION<\/jats:title>\n                    <jats:p>ClinicalTrials.gov NCT01712945.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>FUNDING<\/jats:title>\n                    <jats:p>MRC and Moulton Charitable Trust.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1172\/jci.insight.125377","type":"journal-article","created":{"date-parts":[[2019,5,7]],"date-time":"2019-05-07T13:39:42Z","timestamp":1557236382000},"source":"Crossref","is-referenced-by-count":28,"title":["Keratinocyte growth factor impairs human thymic recovery from lymphopenia"],"prefix":"10.1172","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4738-0760","authenticated-orcid":true,"given":"Alasdair J.","family":"Coles","sequence":"first","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1252-8828","authenticated-orcid":true,"given":"Laura","family":"Azzopardi","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Onajite","family":"Kousin-Ezewu","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harpreet Kaur","family":"Mullay","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara A.J.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5760-0125","authenticated-orcid":true,"given":"Lorna","family":"Jarvis","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8888-1441","authenticated-orcid":true,"given":"Jessica","family":"Davies","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Howlett","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4931-3289","authenticated-orcid":true,"given":"Daniel","family":"Rainbow","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Babar","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy J.","family":"Sadler","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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