www.elsevier.com/locate/yclim ISSN 1521-6616 Volume 262S, May 2024 Selected Abstracts from the 2024 Clinical Immunology Society Annual Meeting: Immune Deficiency and Dysregulation North American Conference May 1–4, 2024 Minneapolis, Minnesota, USA
Volume 250S, 2023 Amsterdam • Boston • London • New York • Oxford • Paris • Philadelphia • San Diego • St. Louis Volume 250S, 2023 Amsterdam • Boston • London • New York • Oxford • Paris • Philadelphia • San Diego • St. Louis Volume 262S, 2024 Selected Abstracts from the 2024 Clinical Immunology Society Annual Meeting: Immune Deficiency and Dysregulation North American Conference May 1–4, 2024 Minneapolis, Minnesota, USA Publication of this supplement was funded by the Clinical Immunology Society. All content was reviewed and approved by the Program Committee, which held full responsibility for the abstract selections.
Co-Editor-in-Chief Samia Khoury American University of Beirut, Beirut, Lebanon Antonio La Cava University of California Los Angeles, Los Angeles, California, USA Advisory Editor George Tsokos, Boston, Massachusetts, USA Associate Editors Iannis Adamopoulos, Boston, Massachusetts, USA Janet Sue Chou, Boston, Massachusetts, USA Jose C. Crispin, Ciudad de México, Mexico Mark Exley, Manchester, UK Lanjuan Li, Hangzhou, China Qianjin Lu, Changsha, China Abhigyan A. Satyam, Boston, Massachusetts, USA Becky M. Vonakis, Baltimore, Maryland, USA Xuan Zhang, Beijing, China Editorial Board Tatiana Akimova David Avigan Dan H. Barouch Jenna Bergerson Elke Bergmann-Leitner George Bertsias Rhea Bhargava Perluigi Bigazzi Patrick Blanco Afroditi Boulougoura Samuele E. Burastero Roberto Caricchio Javier Chinen Daniela Cihakova Dennis Comte Guo-Min Deng Hongyan Diao Wassim Elyaman Lionel Filion Sherry Fleming Shu Man Fu Andrew R. Gennery Christian Hedrich Matthias von Herrath Mitsuomi Hirashima Rodrigo Hoyos Erin Janssen Hirohito Kita Tomohiro Koga Antonio Kolios Michihito Kono Vasileios C. Kyttaris Hao Li Stamatis Nick C. Liossis Mindy Lo Vassilios Lougaris Xiao-Jie Lu Tanya Mayadas Masayuki Mizui Kamal Moudgil Kari Christine Nadeau Haitao Niu Eric Oliver Jordan Orange Mohamed Oukka Andras Perl Shiv Pillai Antony Psarras Thomas Rauen Sergio Rosenzweig Florencia Rosetti Amir Sharabi Nan Shen Lisa A. Spencer Isaac Ely Stillman Elena Svirshchevskaya Yoshiya Tanaka Klaus Tenbrock Betty Tsao George Tsokos Tonya J. Webb Henry Wong Shinsuke Yasuda Nobuya Yoshida Takeshi Yoshida Chack-Yung Yu Maria Tsokos
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Abstracted/indexed in: Biological Abstracts, Chemical Abstracts, Current Contents/Life Sciences, Excerpta Medica, MEDLINE®, PubMed, and SIIC Databases. Also covered in the abstract and citation database Scopus®. Full text available on ScienceDirect®. CONTENTS Available online at www.sciencedirect.com Volume 250, May 2023 Review Pancreatic sympathetic innervation disturbance in type 1 diabetes Senlin Li, Huimin Yuan, Keshan Yang, Qing Li and Ming Xiang 109319 Regular Articles PPAR inhibits small airway remodeling through mediating the polarization homeostasis of alveolar macrophages in COPD Sirong He, Ruoyuan Tian, Xinying Zhang, Qingmei Yao, Quan Chen, Bicui Liu, Lele Liao, Yuxuan Gong, Hua Yang and Dan Wang 109293 STING contributes to traumainduced heterotopic ossification through NLRP3-dependent macrophage pyroptosis Ziyang Sun, Hang Liu, Yuehao Hu, Gang Luo, Zhengqiang Yuan, Bing Tu, Hongjiang Ruan, Juehong Li and Cunyi Fan 109300 Aberrant promoter methylation of Wnt inhibitory factor-1 gene is a potential target for treating psoriasis Liu Liu, Yaqiong Zhou, Dan Luo, Xiaoying Sun, Hongjin Li, Yi Lu, Jiao Wang, Miao Zhang, Naixuan Lin, Chengqian Yin and Xin Li 109294 Myelin basic protein and index for neuro-Behçet's disease Haoting Zhan, Linlin Cheng, Xiaoou Wang, Haiqiang Jin, Yongmei Liu, Haolong Li, Dandan Liu, Xinyao Zhang, Wenjie Zheng, Hongjun Hao and Yongzhe Li 109286 PReS-endorsed international childhood lupus T2T task force definition of childhood lupus low disease activity state (cLLDAS) E.M.D. Smith, A. Aggarwal, J. Ainsworth, E. Al-Abadi, T. Avcin, L. Bortey, J. Burnham, C. Ciurtin, C.M. Hedrich, S. Kamphuis, L. Lambert, D.M. Levy, L. Lewandowski, N. Maxwell, E. Morand, S. Ozen, C.E. Pain, A. Ravelli, C. Saad Magalhaes, C. Pilkington, D. Schonenberg-Meinema, C. Scott, K. Tullus and M.W. Beresford on behalf of the International cSLE T2T Task Force 109296 Baricitinib for the treatment of refractory vascular Behçet's disease Zhimian Wang, Xiaoou Wang, Weiwei Liu, Yuhua Wang, Jinjing Liu, Li Zhang, Shangzhu Zhang, Xinping Tian, Yan Zhao and Wenjie Zheng 109298 κ (continued on inside back cover) Selected Abstracts from the 2024 Clinical Immunology Society Annual Meeting: Immune Deficiency and Dysregulation North American Conference May 1–4, 2024 Minneapolis, Minnesota, USA Late-Breaking Oral Abstracts Friday Poster Abstracts Oral Presentation Abstracts Thursday Poster Abstracts Abstracted/indexed in: Biological Abstracts, Chemical Abstracts, Current Contents/Life Sciences, Excerpta Medica, MEDLINE®, PubMed, and SIIC Databases. Also covered in the abstract and citation database Scopus®. Full text available on ScienceDirect®. CONTENTS Available online at www.sciencedirect.com Volume 250, May 2023 Review Pancreatic sympathetic innervation disturbance in type 1 diabetes Senlin Li, Huimin Yuan, Keshan Yang, Qing Li and Ming Xiang 109319 Regular Articles PPAR inhibits small airway remodeling through mediating the polarization homeostasis of alveolar macrophages in COPD Sirong He, Ruoyuan Tian, Xinying Zhang, Qingmei Yao, Quan Chen, Bicui Liu, Lele Liao, Yuxuan Gong, Hua Yang and Dan Wang 109293 STING contributes to traumainduced heterotopic ossification through NLRP3-dependent macrophage pyroptosis Ziyang Sun, Hang Liu, Yuehao Hu, Gang Luo, Zhengqiang Yuan, Bing Tu, Hongjiang Ruan, Juehong Li and Cunyi Fan 109300 Aberrant promoter methylation of Wnt inhibitory factor-1 gene is a potential target for treating psoriasis Liu Liu, Yaqiong Zhou, Dan Luo, Xiaoying Sun, Hongjin Li, Yi Lu, Jiao Wang, Miao Zhang, Naixuan Lin, Chengqian Yin and Xin Li 109294 Myelin basic protein and index for neuro-Behçet's disease Haoting Zhan, Linlin Cheng, Xiaoou Wang, Haiqiang Jin, Yongmei Liu, Haolong Li, Dandan Liu, Xinyao Zhang, Wenjie Zheng, Hongjun Hao and Yongzhe Li 109286 PReS-endorsed international childhood lupus T2T task force definition of childhood lupus low disease activity state (cLLDAS) E.M.D. Smith, A. Aggarwal, J. Ainsworth, E. Al-Abadi, T. Avcin, L. Bortey, J. Burnham, C. Ciurtin, C.M. Hedrich, S. Kamphuis, L. Lambert, D.M. Levy, L. Lewandowski, N. Maxwell, E. Morand, S. Ozen, C.E. Pain, A. Ravelli, C. Saad Magalhaes, C. Pilkington, D. Schonenberg-Meinema, C. Scott, K. Tullus and M.W. Beresford on behalf of the International cSLE T2T Task Force 109296 Baricitinib for the treatment of refractory vascular Behçet's disease Zhimian Wang, Xiaoou Wang, Weiwei Liu, Yuhua Wang, Jinjing Liu, Li Zhang, Shangzhu Zhang, Xinping Tian, Yan Zhao and Wenjie Zheng 109298 κ (continued on inside back cover) Volume 262S, May 2024 Note: The names of the main authors are underlined. When a main author is not also presenting author, the name of the presenting author is followed by an asterisk.
Late-Breaking Oral Abstracts (210) A multimorphic variant in ThPOK causes a novel human disease characterized by T cell immune developmental abnormalities, immunodysregulation, atopy, and organ fibrosis Maryam Vaseghi-Shanjani*1, Mehul Sharma2, Pariya Yousefi3, Simran Samra4, Kaitlin Laverty5, Arttu Jolma6, Liam Golding3, Rozita Razavi7, AllyYang8, Mihai Albu7, Anna Lee9, RyanTan3, Phillip Richmond10, Marita Bosticardo11, Jonathan Rayment12, Connie Yang9, Kyla Hildebrand9, Rae Brager13, Michelle Demos12, Yu-Lung Lau14, Luigi Notarangelo15, Timothy Hughes16, Remy Bosselut17, Catherine Biggs18, Stuart E. Turvey19 1MD/PhD student/University of British Columbia 2Bioinformatics Scientist/Allen Institute 3Research Assistant/University of British Columbia 4PhD Student/BC Children’s Hospital Research Institute 5Postdoctoral Fellow/University of Toronto 6Post-doctoral fellow/University of Toronto 7Senior Research Associate/University of Toronto 8Lab Manager/University of Toronto 9Clinical Associate Professor/University of British Columbia 10Staff Scientist/University of British Columbia 11Staff Scientist/LCIM/NIAID/NIH 12Clinical Assistant Professor/University of British Columbia 13Associate Professor/McMaster University 14Professor/The University of Hong Kong 15Chief, Laboratory of Clinical Immunology and Microbiology/National Institutes of Health, National Institute of Allergy and Infectious Diseases 16Professor/University of Toronto 17Senior Investigator/National Institutes of Health, Center for Cancer Research, National Cancer Institute 18Clinical Immunologist/BC Children’s Hospital 19Professor/The University of British Columbia The role of the transcription factor ThPOK has not been formally established in humans since individuals with ThPOK deficiency or other damaging variants in ThPOK have not yet been identified. Recent research highlights the critical role of ThPOK in modulating T cell differentiation by promoting CD4 T cell development and suppressing CD8 T cell differentiation. Here, we report the first case of a human with a damaging variant in ThPOK causing a syndrome encompassing CD4 T cell deficiency, allergic disease, severe fibrotic interstitial lung disease, global developmental delay, and growth failure. Trio whole-genome sequencing revealed a de novo variant (NM_001256455.2:c.1080A>C, p.K360N) in ZBTB7B, encoding ThPOK. The expression of ThPOKK360N remained unaffected but functional investigations demonstrated multimorphic activity of ThPOKK360N. Specifically, ThPOKK360N showed dominant-negative activity, interfering with the ability of ThPOKWT to drive the expression of its known targets, SOCS1 and COL2A1 (antimorph). Assays assessing protein-DNA interactions revealed that ThPOKK360N lacked the ability to bind WT consensus sequences in an EMSA (hypomorph). ThPOKK360N also demonstrated neomorphic properties in its DNA-binding specificity confirmed by HT-SELEX, ChIP-seq, and RNA-seq (neomorph). Single-cell seq confirmed patient’s CD4 T cell deficiency, also showing that the majority of the T cells remained at an early differentiation stage compared to healthy controls. In addition, naive CD4 and CD8 T cells exhibited reduced activation response following stimulation. The causal relationship between ThPOKK360N and patient’s phenotype was established through lentiviral transduction of healthy control Tcells and pulmonary fibroblasts. Tcells transduced with ThPOKWT showed upregulation of genes in activation, proliferation, and interferon effector pathways, a response largely absent in cells transduced with ThPOKK360N. Overexpression of ThPOKWTand ThPOKK360N in fibroblasts revealed distinct gene expression profiles, with ThPOKK360N upregulating pro-fibrotic genes implicated in pulmonary fibrosis (ACTA2, TGFB1, LTBP2, BDNF, and COL1A1). This description of a novel IEI caused by a multimorphic variant in ThPOK confirms its role in CD4 T cell development in an intact human context, while also revealing an unanticipated role for ThPOK in fibrosis. We anticipate this discovery will accelerate the diagnosis of additional affected individuals, helping to reveal the full spectrum of human ThPOK-related disorders. Keywords: Inborn error of immunity, Primary atopic disorder, CD4 T cell deficiency, Allergy, Transcription factor, Combined immunodeficiency, Fibrosis, Interstitial lung disease, ThPOK, T cell development Clinical Immunology 262S (2024) 110152 https://doi.org/10.1016/j.clim.2024.110152 (211) Biallelic null mutations in PPM1D cause a novel combined immunodeficiency with severe neurodevelopmental defects Ana Esteve Sole*1, Luis Ignacio González-Granado2, Brigette Boast1, Julie E. Niemela3, Jennifer L. Stoddart3, Agustin G. Silva4, Leticia Pias5, Merce Bolasell6, Ana V. Marin7, Jose R Regueiro8, Laia Alsina9, Pierre Martine10, Kate Brown11, Ettore Apella12, Juan Francisco Quesada13, Colin L Sweeney14, Harry Malech15, Cathryn L Haigh16, HyeSun Kueh3, Sergio Rosenzweig17 1Postdoctoral fellow/Immunology Service, Department of Laboratory Medicine, Clinical Center, National Institutes of Health 2Head of the Primary Immunodeficiencies Unit/Research Institute Hospital 12 Octubre. Immunodeficiency Unit, Department of Pediatrics, University Hospital 12 de Octubre, Madrid, Spain 3Staff Scientist/Immunology Service, Department of Laboratory Medicine, Clinical Center, National Institutes of Health 4Technician/Immunology Service, Department of Laboratory Medicine, Clinical Center, National Institutes of Health 5Neuropediatrician/Neurometabolic Unit and Department of Genetic and Molecular Medicine, Hospital Sant Joan de Déu, Barcelona, Spain Clinical Immunology 262S (2024) Abstracts CIS 2024 Contents lists available at ScienceDirect Clinical Immunology journal homepage: https://www.elsevier.com/locate/yclim 1521-6616/© 2024 Elsevier Inc. All rights reserved. 1
6Biologist/Department of Genetic and Molecular Medicine IPER, Institut de Recerca, Hospital Sant Joan de Déu Barcelona, Barcelona, Spain 7Associated Researcher/Department of Immunology, Complutense University School of Medicine and Hospital 12 de Octubre Health Research Institute, Madrid, Spain 8Vicedecano de Investigación y Doctorado/Department of Immunology, Complutense University School of Medicine and Hospital 12 de Octubre Health Research Institute, Madrid, Spain 9Head of the Allergy and Immunology Service/Clinical Immunology and Primary Immunodeficiencies Unit. Allergy and Clinical Immunology Department HSJD. Clinical Immunology Unit. HSJD-HCP. Study Group for Immune Dysfunction Diseases in Children (GEMDIP). Institut de Recerca Sant Joan de Déu. Barcelona, Spain 10Postdoctoral fellow/Laboratory of Cell Biology, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland, USA 11Staff Scientist/Laboratory of Cell Biology, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland, USA 12Senior Investigator/Laboratory of Cell Biology, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland, USA 13Facultativo especialista/Department of Genetics, Hospital Universitario 12 de Octubre, Madrid, Spain 14Staff Scientist/Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 15Deputy Chief, LCIM, NIAID/NIH/NIAID 16Chief of the Prion Cell Biology Unit/Prion Cell Biology Unit, Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 17Pediatrician and Clinical immunologist/NIH PPM1D is a phosphatase that regulates the DNA damage response pathway by inhibiting p53 and other proteins through dephosphorylation. Human germline heterozygous variants have been identified as causative of Jansen de Vries (JdV) syndrome, which presents with behavior-related neurodevelopmental/autistic spectrum disorders without immunodeficiency. Here, we present a novel syndromic inborn error of immunity caused by a biallelic PPM1D null mutation. We describe two siblings with progressive B and NK-cell lymphopenia, agammaglobulinemia, non-infectious colitis and severe neurodevelopmental defects including microcephaly. Both carry a homozygous Nterminal truncating variant in PPM1D (p.Thr174fs*6), inherited from their healthy heterozygous consanguineous parents. This variant leads to no endogenous protein detection with a PPM1D-null phenotype. We also evaluated a JdV-causing PPM1D variant (p.S403fs*), observing an overaccumulation of the truncated protein with conserved phosphatase activity, resulting in a gain of function (GOF) effect. Further in vitro testing revealed that PPM1D inhibition in healthy control lymphocytes caused a dramatic decrease in B-cell viability and reduced plasmablast formation, showing the relevance of PPM1D in mature B-cell survival and maturation. B-cell development was evaluated in Ppm1dknock-out (KO) mice, showing a partial arrest in bone marrow B-cell development at the precursor stage, with decreased B-cell frequency in the bone marrow and spleen, supporting the patients’ B-cell lymphopenia phenotype. In addition, Ppm1d-KO mice revealed increased embryonic and perinatal lethality with increased apoptosis in the neural tissue; however, surviving mice did not show gross neurodevelopment defects. Artificial cerebral organoids (ACO) were generated from patient-derived induced pluripotent stem cells (iPSC). The PPM1D-null patient-derived ACO were markedly smaller than the control ACOs, accompanied by reduced cell numbers and a more immature phenotype, supporting the patients’ phenotype. These effects were rescued after pharmacological intervention with pifithrin-a (p53 inhibitor). Contrarily, organoids derived from the PPM1D-GOF patient had conserved cell numbers and a more mature phenotype, in agreement with previously reported results in autistic spectrum disorder patients. Here we describe a biallelic PPM1D-null deficiency causing a novel syndromic disease characterized by B and NK-cell lymphopenia and a severe neurodevelopmental alteration. We also provide proof-of-principle that pharmacological compensation of the defect can modify the neurodevelopmental defects observed in the patients. Keywords: Immunodeficiency, Neurodevelopment, Cerebral organoids, iPS cells, Murine model Clinical Immunology 262S (2024) 110153 https://doi.org/10.1016/j.clim.2024.110153 (212) Human ASXL1 Deficiency Causes Epigenetic Dysfunction, Combined Immunodeficiency and EBV–Associated Hodgkin Lymphoma Maggie Fu*1, Mehul Sharma2, Pariya Yousefi3, Sarah Merrill4, RyanTan3, BhaviModi5, Kate L. Del Bel6, Rebecca Deyell7, Jacob Rozmus8, Wingfield Rehmus7, Kyla Hildebrand7, Elliot James9, Geraldine Blanchard-Rohner10, Susan Lin3, Kevin Shopsowitz11, Audi Setiadi8, Jefferson Terry7, Anna Lee7, Britt Drögemöller12, Allison Matthews8, Maja Tarailo-Graovac13, Laura Sauvé8, Hana Mitchell8, Julie Prendiville14, Julie MacIsaac15, Kristy Dever15, David Lin16, Mandy Meijer17, Colin Ross18, Simon Dobson7, Suzanne Vercauteren19, Wyeth Wasserman18, Clara van Karnebeek20, Margaret McKinnon8, Michael Kobor18, Stuart E. Turvey21, Catherine Biggs8 1PhD Student/University of British Columbia 2Post Doctoral Fellow/Allen Institute of Immunology 3Research Assistant/University of British Columbia 4Postdoctoral Fellow/Brown University 5Research Associate/BC Children’s Hospital 6Research Manager/University of British Columbia 7Clinical Associate Professor/University of British Columbia 8Clinical Assistant Professor/University of British Columbia 9Pediatric Clinical Immunologist/BC Children’s Hospital 10Division Head/Unit of Immunology and Vaccinology, Division of General Pediatrics, Department of Pediatrics, Gynecology and Obstetrics, Geneva University Hospitals and University of Geneva, Geneva, Switzerland 11Resident Physician/University of British Columbia 12Assistant professor/University of Manitoba 13Associate Professor/University of Calgary 14Pediatric Dermatologist/BC Children’s Hospital 15Research Scientist/University of British Columbia 16Scientist/AbCellera 17Postdoctoral Fellow/University of British Columbia 18Professor/University of British Columbia 19Clinical Professor/University of British Columbia 20Affiliate Professor/University of British Columbia 21Professor/The University of British Columbia Inborn errors of immunity (IEI) are a group of disorders caused by deleterious variants in immune-related genes, including some that function as epigenetic regulators. Additional sex combs-like 1 (ASXL1) is an epigenetic modifier that has not previously been linked to an IEI. Somatic ASXL1 variants are found in clonal hematopoiesis and hematologic neoplasms, while heterozygous germline variants cause Bohring–Opitz syndrome. We present a new IEI caused by biallelic germline variants in ASXL1. The patient had a complex and unusual history of disease progression notable for severe and persistent cutaneous vaccine-strain Clinical Immunology 262S (2024) Abstracts CIS 2024 2
rubella granulomas initially manifesting at age 3 years, chronic macrocytosis and mild bone marrow cellular hypoplasia, and Epstein Barr virus– associated Hodgkin lymphoma in adolescence. Detailed immunophenotyping revealed progressive loss of B-cells, hypogammaglobinemia, and Tcell lymphopenia with severe skewing toward a memory phenotype and elevated expression of T-cell exhaustion and senescence markers. Molecular investigations confirmed ASXL1 protein deficiency in the patient’s T-cells and fibroblasts. The T-cells exhibited marked loss of DNA methylation, increased epigenetic aging, and CD8 T-cell dysfunction. These aberrations were ameliorated by lentivirus-mediated transduction with wild-type ASXL1, confirming the pathogenicity of ASXL1 variants. This study defined a novel human IEI caused by ASXL1 deficiency, a diagnosis that should be considered in individuals with chronic viral infections, virusassociated hematologic malignancies, and combined immunodeficiency. Furthermore, our findings provide fresh insights into the mechanisms underlying the roles of human ASXL1 in T-cell function as well as in the development and maintenance of lymphomas. Keywords: Inborn error of immunity, ASXL1, Combined immunodeficiency, Hodgkin lymphoma, Epigenetics Clinical Immunology 262S (2024) 110154 https://doi.org/10.1016/j.clim.2024.110154 (213) IKAROS negatively regulate memory T cell formation in humans Ravichandra Tagirasa*1, HyeSun Kueh2, Marita Bosticardo3, Francesca Pala4, Kayla Amini5, Eduardo Anaya6, Jennifer Stoddard7, Julie Niemela8, Laia Alsina9, Mario Framil Seoane10, Dimana Dimitrova11, Matias Oleastro12, Carolina Bouso12, Richard L Wasserman13, Luigi Notarangelo14, Sergio Rosenzweig15 1Post-Doctoral Fellow/NIH 2Staff Scientist/Immunology Service, Department of Laboratory Medicine, Clinical Center, National Institutes of Health 3Staff Scientist/LCIM/NIAID/NIH 4Research Fellow/NIH 5Post-baccalaureate Research Fellow/NIH/NIAID 6Postbaccalaureate Fellow/NIH/NIAID 7Research Scientist/NIH/CC 8Research Biologist/National Institutes of Health 9Physician Researcher/Clinical Immunology and Primary Immunodeficiencies Unit, Pediatric Allergy and Clinical Immunology Department, Hospital Sant Joan de Déu, Barcelona, Spain; Institut de Recerca Sant Joan de Déu, Barcelona, Spain; Clinical Immunology Unit Hospital Sant Joan de Déu-Hospital Clínic Barcelona, Barcelona, Spain 10Research biologist/Barcelona Clinic 11Pediatric Immunologist and Allergist/Center for Immuno-Oncology, National Cancer Institute 12Research Scientist/Garrahan Pediatric Hospital 13Medical Director/Allergy Partners of North Texas Research, Dallas, TX, USA 14Chief, Laboratory of Clinical Immunology and Microbiology/National Institutes of Health, National Institute of Allergy and Infectious Diseases 15Pediatrician and Clinical immunologist/NIH IKAROS, is a zinc finger (ZF) transcription factor encoded by IKZF1, expressed throughout hematopoiesis. Patients with heterozygous germline IKZF1 mutations have progressive B cell deficiency and impaired immune functions, leading to recurrent infections, immune dysregulation, and an increased risk of malignancies. However, the role of IKAROS in T cell maturation and differentiation is not fully understood. In this study, we discovered that patients with mutations in IKAROS have defects, particularly affecting the generation of naive (CD45RA+) and memory (CD45RO+) T cell phenotypes. Remarkably, patients with loss-of-function (LOF) variants (N159K, H167R and Y503*) mainly presented with increased memory T cells, skewed towards Th1 subset, and markedly decreased naive T cells. However, the dominant negative variant (N159S) manifests mainly with naive T cells, which is due to impairment in T cell activation and proliferation. Unlike the LOF variants, the IKAROS gain-of-function (GOF) variant R183C primarily manifests with naive T cells. Additionally, to mimic the LOF mutations in vitro, we degraded IKAROS through lenalidomide or knocked-down IKZF1 by lentiviral shRNA, resulting in a significant increase in memory T cell formation from naive T cells. To further study the role of IKAROS in early T cell maturation and differentiation in the thymus, artificial thymic organoids were generated from patient CD34+ cells, which clearly revealed that IKAROS LOF variants induce generation of CD45RO+ T cells even at the early stages of T cell development in thymus, when T cell progenitors normally have a CD45RA+ phenotype. Mechanistically, splicing of CD45RA in to CD45RO in activating T cells is mediated by heterogeneous nuclear ribonucleoprotein L-like (hnRNPLL), here we demonstrated that IKAROS inhibits the expression of hnRNPLL and LOF mutations or degradation of IKAROS by lenalidomide releases this inhibition. Altogether, here we illustrate that IKAROS negatively regulates hnRNPLL there by memory T cell generation. Importantly, these insights suggest that targeted degradation of IKAROS could be exploited to generate robust homogenic memory T cells, which is one of the challenges in CAR T cell generation. Keywords: IKAROS, CD45RA, CD45RO, hnRNPLL, Artificial thymic organoids, Memory T cells, CAR T cells Clinical Immunology 262S (2024) 110155 https://doi.org/10.1016/j.clim.2024.110155 (214) ICOS Agonist Vopratelimab Modulates Follicular Helper T Cells and Improves B Cell Function in Common Variable Immunodeficiency Ali Sepahi1, Hsi-enHo2, Prapti Vyas3, Benjamin Umiker4, Katalin Kis-Toth5, Dmitri Wiederschain6, Lin Radigan7, Charlotte Cunningham-Rundles*8 1Senior Scientist, Translational Immunology/PharmaEssentia Innovation Research Center 2Assistant Professor/Icahn School of Medicine at Mount Sinai 3Senior Research Associate/ReNAgade Therapeutics 4Director, Translational Medicine Lead/AstraZeneca 5Vice President, Translational Medicine/NextPoint Therapeutics, Inc 6Chief Scientific Officer, Crossbow Therapeutics/Vopralilamab revised markedCCR.AS trial 7Research Associate/Icahn School of Medicine at Mount Sinai 8David S Gottesman Professor/Mount Sinai Common variable immunodeficiency (CVID) is an immune defect characterized by hypogammaglobulinemia and impaired development of B cells into antibody-secreting memory B cells and plasma cells. As follicular helper T cells (TFH) play a central role in humoral immunity, we examined TFH cells in CVID, and investigated whether an ICOS agonist, vopratelimab, could modulate TFH, B cell interactions and enhance immunoglobulin production. CVID subjects had decreased TFH17 and increased TFH1 subsets; this was associated with increased transitional B cells and decreased IgG+ B and IgD- CD27+ memory B cells. ICOS expression in CVID CD4+ T cells was also decreased. However, ICOS activation of CD4+ T cells by vopratelimab significantly increased total CVID TFH, TFH2, cell numbers, IL-4, IL-10 and IL-21 secretion in vitro. Vopratelimab treatment also increased plasma cells, IgG+ B cells, reduced naïve & transitional B cells and significantly increased IgG1 secretion by CVID B cells. Interestingly, Clinical Immunology 262S (2024) Abstracts CIS 2024 3
vopratelimab treatment also restored IgA secretion in PBMCs from several CVID patients who had a complete lack of endogenous serum IgA. Our data demonstrate the potential of TFH modulation in restoring TFH and enhancing B cell maturation in CVID. The effects of an ICOS agonist in primary antibody defects warrants further investigation; this biologic may also be of therapeutic interest in other clinical settings of antibody deficiency. Keywords: Common variable immune deficiency, Inducible T cell costimulator (ICOS) activation, Follicular helper T cells, IL-10 and IL-21 secretion, IgG1 production, Follicular helper T cell modulation Clinical Immunology 262S (2024) 110156 https://doi.org/10.1016/j.clim.2024.110156 Clinical Immunology 262S (2024) Abstracts CIS 2024 4
Friday Poster Abstracts (1) A novel CARD9-deficiency mouse model recapitulates chronic CNS candidiasis and identifies defective monocytic-cell responses in immunopathogenesis Donald Vinh*1, Marija Landekic2, Isabelle Angers3, Yongbiao Li3, Lucie Roussel4, Marie-Christine Guiot5, Michail Lionakis6, Robert Wheeler7, IrahKing8, Salman Qureshi9, Maziar Divangahi10 1Associate Professor, Clinician-Scientist/McGill University Health Centre 2Post-Doctoral Fellow/Research Institute - McGill University Health Centre 3Research Assistant/Research Institute - McGill University Health Centre 4Research Associate/Research Institute - McGill University Health Centre 5Pathologist/McGill University Health Centre 6Chief, Fungal Pathogenesis Section/NIH 7Associate Professor/University of Maine 8Associate Professor/Research Institute - McGill University Health Centre 9Associate Professor/McGill University Health Centre 10Professor/McGill University Human CARD9 deficiency is a recessive inborn error of immunity that manifests with susceptibility to invasive fungal disease. Enigmatically, it often presents as an adult-onset, indolent disease with candidal brain abscess/meningo-encephalitis, what we have previously termed “spontaneous central nervous system candidiasis (sCNSc)”. The immunopathogenic basis for this manifestation is poorly understood. While CARD9-null mouse platforms have unambiguously shown that CARD9 influences disease susceptibility and severity to Candida, this approach is not an accurate model of disease in that mice die of fulminant multi-organ dysfunction, of which the brain is one of many organs infected. This course does not mirror the human disease, imploring the need for a more accurate model to study immunopathogenesis. Here, we generated a mouse homozygous for the recurring human p.Y91H mutation; using it and the null mouse, we titrated the candidal challenge to the CARD9 genotype. Through clinical, radiological, and histological analyses, we show that this approach creates mouse models that phenocopy the human disease. We then used this model to demonstrate that monocytic-cells (Ly6C+ monocytes and bone-marrow derived macrophages) are aberrant in anticandidal responses. We also identify subtle immunologic disturbances between the hypomorphic (p.Y91H) and null mice, which we believe may shed light on some of the clinical variability seen in CARD9-deficient humans. This clinically-accurate, CARD9-deficient mouse model will enable a better understanding of fungal disease pathogenesis and the rational development of therapeutic interventions. Keywords: CARD9, Candidiasis, Fungal, Mouse model Disclosures: Donald Vinh: I have relevant financial relationships with proprietary interests: AstraZeneca (Advisory Board); GSK (Advisory Board); Moderna (Advisory Board); Takeda (Advisory Board). The other authors have no financial relationships or conflicts of interest to report. Clinical Immunology 262S (2024) 109943 https://doi.org/10.1016/j.clim.2024.109943 (2) Maternal and neonate outcomes following exposure to hyaluronidasefacilitated subcutaneous immunoglobulin 10% during pregnancy: a retrospective case series based on US claims data Krista Huybrechts1, JinXia2, William Spalding*3, Sonia Hernández-Díaz4 1Associate Epidemiologist/Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA 2Associate Director/Takeda Development Center Americas, Inc., Cambridge, MA, USA 3Head of Safety Pharmacoepidemiology/Takeda Development Center Americas, Inc., Cambridge, MA, USA 4Professor of Epidemiology/Harvard T.H. Chan School of Public Health, Boston, MA, USA The efficacy and safety of hyaluronidase-facilitated subcutaneous immunoglobulin 10% (fSCIG 10%; HYQVIA) in primary immunodeficiency diseases are well documented in the general population. However, data are limited on the safety of fSCIG 10% during pregnancy. In this retrospective, noninterventional, administrative claims database study, we sought to describe maternal and neonate characteristics and outcomes following exposure to fSCIG 10% during pregnancy. De-identified data from the US MarketScan Research Database between January 1, 2014 and December 31, 2021 were used to identify all women (ages 16–44 years) exposed to fSCIG 10% during pregnancy. Pregnancy losses and livebirths were identified using inpatient and outpatient fetal loss or delivery-related diagnostic and procedure codes. Exposure was defined based on filled prescriptions or infusion of fSCIG 10% from 90 days before the last menstrual period until the end of pregnancy. Among approximately 1.9 million pregnancies recorded in the database during the study period, seven pregnancies (6 patients with immunodeficiency diseases aged between 24 and 40 years) were exposed to fSCIG 10%. Five pregnancies were exposed to fSCIG 10% throughout pregnancy; one pregnancy was exposed during the first trimester only and one pregnancy during the second and third trimesters only. For all patients, there was evidence of multiple infections and concomitant medication use during pregnancy. Out of the seven pregnancies identified, six ended in a single livebirth at term (38–40 weeks). One pregnancy ended in spontaneous abortion at 9 gestational weeks in a patient with a history of recurrent pregnancy loss. No unusual pattern of complications or adverse events was identified. Of the six newborns, four were linked to maternal records and were followed for 3 months. In these four neonatal records, there were no codes for major congenital Clinical Immunology 262S (2024) Abstracts CIS 2024 Contents lists available at ScienceDirect Clinical Immunology journal homepage: https://www.elsevier.com/locate/yclim 1 1521-6616/© 2024 Elsevier Inc. All rights reserved.
abnormalities, small size for gestational age, or admission to the neonatal intensive care unit. This clinical case series, extracted from a large claims database, does not raise concerns regarding the safety of fSCIG 10% use during pregnancy. However, more evidence is needed to narrow the uncertainty around these initial observations. Study funder: Takeda Development Center Americas, Inc. Writing support funder: Takeda Pharmaceuticals International AG. Keywords: Database, fSCIG, Hyaluronidase, Immunoglobulin G, Inborn errors of immunity, Immunodeficiencies Disclosures: Krista Huybrechts: I have relevant financial relationships with proprietary interests: Takeda (Grants/Research Support Recipient). Jin Xia: I have relevant financial relationships with proprietary interests: Takeda Development Center Americas, Inc. (Employee); Takeda Development Center Asia (Employee). William Spalding: I have relevant financial relationships with proprietary interests: Takeda Development Center Americas, Inc. (Employee). Sonia Hernández-Díaz: I have relevant financial relationships with proprietary interests: Johnson & Johnson (Consultant); Moderna (Consultant); Takeda (Grants/Research Support Recipient); UCB (Consultant). Clinical Immunology 262S (2024) 109944 https://doi.org/10.1016/j.clim.2024.109944 (3) Development of the Canadian Inborn Errors of Immunity National Registry (CIEINR) Tatiana Kalashnikova*1, Taylor Mattison2, Alyssa Alger3, Mandi Uppal4, Eyal Grunebaum5, Sneha Suresh6, Bruce Ritchie7, Juthaporn Cowan8, Tamar Rubin9, Luis Murguia-Favela10, Jennifer Grossman11, CarenWu11, Hugo Chapdelaine12, Kevin Lee13, Catherine Biggs14, Rae Brager15, Ashley V. Geerlinks16, Whitney Goulstone17, Beata Derfalvi18, Nicola Wright19 1Clinical Research Fellow in Clinical Immunology/University of Calgary 2Medical Student/Dalhousie University, Halifax, Nova Scotia, Canada 3Nurse Practitioner/Collaborative Immunology Program, Foothills Hospital, Calgary, Alberta, Canada 4Analyst/Alberta Health Services 5Clinical Immunology/Hospital for Sick Children 6Assistant Professor/University of Alberta 7Professor/University of Alberta 8Associate Professor/Department of Medicine, University of Ottawa 9Assistant Professor/University of Manitoba 10Clinical Associate Professor. Pediatric Immunology/Alberta Children’s Hospital, University of Calgary 11Clinical Assistant Professor/University of Calgary 12Clinical associate professor/Montreal Clinical Research Institute, University of Montreal 13Physician/N/A 14Clinical Immunologist/BC Children’s Hospital 15Associate Professor/McMaster University 16Physician/University of Western Ontario 17Executive Director/Immunity Canada 18Professor/IWK Health Centre/Dalhousie University 19Clinical Associate Professor/University of Calgary Introduction: It is estimated that 29,000 Canadians live with monogenic or polygenic inborn errors of immunity (IEI). Canada has a unique IEI population with specific founder mutations including those in First Nations, Métis, Inuit (FNMI), and Mennonites as well as diverse immigrant communities. As has been highlighted as a major deficiency by patient organizations, there is no comprehensive portrait of patients with IEI in Canada. Our aim is to develop the Canadian IEI National Registry (CIEINR) to standardize data collection to better understand the landscape of IEI in Canada. Methods: The Registry Working Group (RWG) of the Clinical Immunology Network - Canada (CINC), with input from the national patient organization ‘ImmUnity Canada’, organized registry development into 7 phases (Fig. 1). Consensus was reached on a longitudinal, patient-focused study design and the protocol was externally peer-reviewed. Multi-level data collection tools, with annual updates on demographics, infectious and non-infectious manifestations, laboratory values, treatment, quality of life (PROMIS survey), and patient-reported outcomes have been developed. Data forms were based on those developed by the Collaborative Immunology Program, Southern Alberta, and align with the United States Immunodeficiency Network (USIDNET) and European Society for Immunodeficiencies (ESID) registry forms. Adolescents will complete an ‘Adolescent- ready to Transition Questionnaire’ created by the University of British Columbia team. De-identified data will be collected in RedCap, with the data center housed at the University of Calgary. Sites will be able to query the data via request submitted to the Working Group. Figure 1. Development phases of the Canadian Inborn Errors of Immunity National Registry (CIEIN). Results: Ethics approval has been obtained or is in process at several sites and legal agreements are in process. Data collection is being piloted at several sites with a variety of pediatric and adult cases; initial data is included in Table 1. Clinical Immunology 262S (2024) Abstracts CIS 2024 2
Table 1. Canadian Inborn Errors of Immunity National Registry Pilot Data. Characteristics Pediatric Cohort* Adult Cohort** Recruited participants 20 42 Sex n (%) n (%) Male 12 (60) 10 (24) Female 8 (40) 32 (76) Median (range) Median Age at the time of symptom onset (years) 1 (0.08–4) n/a Age at the time of diagnosis (years) 5 (1–15) n/a Mean (SD) Median (range) Age at last visit (years) 11 (5.1) 63 (18–77) Diagnosis (IUIS classification) n (%) n (%) 1. Predominantly antibody deficiency 15 (75) 30 (71) CVID with no gene defect specified 10 (50) 17 (40) Selective antibody deficiency (IgA/IgM deficiency) 1 (5) 9 (21) X-linked agammaglobulinemia with an associated BTK mutation 2 (10) n/a Hypogammaglobulinemia with absent B cells, no genetic evaluation n/a 3 (7) TACI deficiency 2 (10) n/a APDS n/a (2) 2. Immunodeficiencies affecting cellular and humoral immunity n/a 2 (5) Low CD4 count n/a 2 (5) 3. CID with associated syndromic features 1 (5) 4 (9.5) SPNS2 deficiency 1 (5) n/a Hyper-IgE syndrome n/a 4 (9.5) 4. Auto-inflammatory disorders 1 (5) n/a ADA2 deficiency 1 (5) n/a 5. Diseases of immune dysregulation 3 (15) n/a XMEN 2 (10) n/a LRBA deficiency 1 (5) n/a 6. Phenocopies of PID n/a 2 (5) Good’s syndrome n/a 2. (5) 7. Secondary immune deficiencies n/a 3 (9.5) Immunoglobulin replacement therapy n (%) n (%) IVIG 9 (45) 7 (17) SCIG 11 (55) 21 (50) Infections in the last 12 months n (%) n (%) Respiratory tract infections (sinusitis, pneumonia) 11 (55) 26 (62) Gastrointestinal infections 2 (10) 19 (45) Ear infections 9 (45) 5 (12) Skin infections n/a 3 (7) Abscess n/a 5 (12) *Pediatric Immunology Clinic, Dalhousie University, Halifax, NS. **Adult Immunology Clinic, Collaborate Immunology Program of Southern Alberta, Foothills Hospital, Calgary, AB. ADA2 deficiency- adenosine deaminase 2 deficiency, APDS-activated p110δ syndrome, CID -combined immune deficiency, CVID -common variable immune deficiency, IVIG– intravenous immunoglobulin, LRBA deficiency - lipopolysaccharide-responsive and beige-like anchor protein deficiency, PID -primary immune deficiency, SCIG– subcutaneous immunoglobulin, SPNS2 deficiency- Spinster homolog 2 deficiency, TACI deficiency - hypogammaglobulinemia due to TNFRSF13B mutation, XMEN-X-linked immunodeficiency and magnesium defect, EBV and neoplasia. Conclusion: The information collected in the CIEINR will be essential to analyze unique features of IEI in Canada and will provide a strategic method to optimize patient care and improve access to novel therapies and clinical trials. Registry data will provide a tool to assess barriers to medical care, particularly for those in rural/remote regions, and will be vital to support advocacy for resource allocation. Keywords: Registry, Inborn Errors of Immunity, Canada Disclosures: Bruce Ritchie: I have relevant financial relationships with proprietary interests: Biocryst (Advisory Board); CSL Behring (Advisory Board, Clinical Trial Investigator, Research Grant (includes principal investigator, collaborator or consultant and pending grants as well as grants already received); Ionis (Clinical Trial Investigator); Mitsubishi Tanabe (Clinical Trial Investigator); NovoNordisk (Clinical Trial Investigator); OctaPharma (Advisory Board, Clinical Trial Investigator, Research Grant (includes principal investigator, collaborator or consultant and pending grants as well as grants already received)); Pfizer (Advisory Board, Research Grant (includes principal investigator, collaborator or consultant and pending grants as well as grants already received)); Pharvaris (Clinical Trial Investigator). Juthaporn Cowan: I have relevant financial relationships with proprietary interests: AstraZeneca (Medical writing, Speaker/Honoraria (includes speakers bureau, symposia, and expert witness)); Avir Pharma (Speaker/Honoraria (includes speakers bureau, symposia, and expert witness)); CSL Behring (Consulting Fees (e. g., advisory boards)); GSK (Consultant); Merck (Consulting Fees (e.g., advisory boards)); Octapharma (Travel expense); Pfizer (Speaker/ Honoraria (includes speakers bureau, symposia, and expert witness)); Takeda (Advisory Board, Speaker/Honoraria (includes speakers bureau, symposia, and expert witness)). Luis Murguia-Favela: I have relevant financial relationships with proprietary interests: ENCODED Therapeutics (Data Safety Monitoring Committee Member). Beata Derfalvi: I have relevant financial relationships with proprietary interests: Pharming (Consultant); Takeda (Consultant). The other authors have no financial relationships or conflicts of interest to report. Clinical Immunology 262S (2024) 109945 https://doi.org/10.1016/j.clim.2024.109945 (4) A novel BNLK mutation presenting with hepatopathy and rickets HulyaKose1, Yasin Karali1, Sara Kilic*2 1MD/Bursa Uludag University 2Head of Pediatric Immunology/Uludag University Medical Faculty BLNK represents a central linker protein that bridges the B cell receptor– associated kinases with a multitude of signaling pathways and may regulate the biologic outcomes of B cell function and development. Blnk deficiency is a type of autosomal recessive immune disorder that involves the absence of B cells, agammaglobulinemia, and recurrent infections. Only ten patients with BLNK deficiency have ever been identified. We present a 29-year-old Turkish female with BLNK deficiency with a novel homozygous CGA > TGA codon123, exon6) mutation in the BLNK gene. She developed severe liver failure and rickets at the age of 12. Although BLNK mutations are rare causes of agammaglobulinemia, it is important to consider them in patients with B cell deficiency. She is the first to be described with hepatopathy and bone metabolism disorder in BLNK deficiency in the literature. Hepatopathy and rickets, seen in this case, are clinical conditions that should be considered in BLNK deficiency. Keywords: BLNK deficiency, Inborn errors of Immunity, Liver failure, Rickets, Hepatopathy Disclosures: The authors have no financial relationships or conflicts of interest to report. Clinical Immunology 262S (2024) 109946 https://doi.org/10.1016/j.clim.2024.109946 Clinical Immunology 262S (2024) Abstracts CIS 2024 3
(5) How do non-infectious presentations begin in patients with Inborn Errors of Immunity? David Lobo*1, Ricardo Cesar Vieira Madeiro Filho2, Thais Costa Lima de Moura2, Mayra de Barros Dorna2, Ana Paula Beltran Mosquione Castro2, Antonio Carlos Pastorino2 1Allergist and Immunologist Pediatrician/Children’s Institute/Clinical Hospital of São Paulo University 2Allergist and Immunologist Pediatrician/Children’s Institute - Clinical Hospital of São Paulo University Background: Non-infectious presentations may be the first data for the clinical suspicious of Inborn Errors of Immunity (IEI) and their recognition may contribute to an early diagnosis. We aim to describe the non-infectious presentations in patients with diagnosis of IEI. Methods: We analyze medical records of patients with diagnosis of IEI followed at a Tertiary Pediatric Hospital between 2018–23. Patients were included if they had only initial non-infectious presentations related to the disease. We divided these presentations in 5 groups: 1. Syndromic Presentations (such as heart disease and facial abnormalities). 2. Immune Dysregulation Presentations (such as lymphoproliferation and autoimmune cytopenias). 3. Blood Count Changes (such as pancytopenia and isolated cytopenia). 4. Family History of IEI (reported before any clinical manifestation). 5. Changes in T-Cell Receptor Excision Circles (TRECs). We then describe the specific initial presentations in each group and the ages at which they began. Figure 1. Results: Of the 177 patients (45M) with diagnose of IEI, 78 patients (44%) were included. 53 presented before 1yo and 25 between 1 and 5yo. 91 non-infectious initial presentations were reported in these 78 patients (due to overlapping) as follow: • Syndromic Presentations (48): [Heart disease (30), eczema (6), ataxia (5), facial abnormalities (4) and bleeding (3)]. • Immune Dysregulations (20): [Lymphoproliferation (12), autoimmune cytopenias (3), hemophagocytic lymphohistiocytosis (3) and inflammatory bowel disease (2)]. • Blood Count Changes (13): [Thrombocytopenia (7), pancytopenia (4) and neutropenia (2)]. • Family History (7). • Changes in TRECs (3). The distribution of age at onset of presentations in each group was: Syndromic Manifestations (38 before 1yo and 10 between 1 and 5yo); Immune Dysregulation (5 before 1yo and 15 between 1 and 5yo); Blood Count Changes (8 before 1yo and 5 between 1 and 5yo); Family History of IEI (7 before 1yo) and Changes in TRECs (3 before 1yo). Figure 2. Conclusion: The initial non-infectious presentations of IEI were frequent and early (mainly in the first year of life). Knowledge of the different clinical features and laboratory findings is essential for improve the suspicious and make and early diagnosis, enabling strategies to improve the prognosis of patients. Keywords: Immunodeficiency, Noninfectious, Immune dysregulation, TRECs Disclosures: The authors have no financial relationships or conflicts of interest to report. Clinical Immunology 262S (2024) 109947 https://doi.org/10.1016/j.clim.2024.109947 (6) A Case of CGD Colitis: Sparing Steroids and Colectomy Victoria Nguyen*1, Peter Mustillo2 1Fellow/The Ohio State University/Nationwide Children’s Hospital 2Attending Physician/Nationwide Children’s Hospital Introduction: Chronic granulomatous disease (CGD) is a rare immunodeficiency resulting in inability of phagocytes to kill ingested catalasepositive organisms, predisposing patients to recurrent bacterial and fungal infections. X-linked CGD is associated with at least a 50% risk of developing bowel inflammation resembling inflammatory bowel disease (IBD). Tumor necrosis factor (TNF) inhibitors, when used for CGD colitis, have been associated with increased mortality related to severe infection susceptibility, which limits treatment options. We present a case of a patient with CGD colitis that achieved remission with the addition of high dose vedolizumab. Case Description: We present a case of a 22-year-old male diagnosed with X-linked CGD at age 4 months after presenting with cervical lymphadenitis. He developed CGD colitis with perirectal abscess requiring diverting Clinical Immunology 262S (2024) Abstracts CIS 2024 4
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