"Deficiency in ELF4, X-Linked: a Monogenic Disease Entity Resembling Beh?et's Syndrome and Inflammatory Bowel Disease"

作者全名："Olyha, Sam J.; O'Connor, Shannon K.; Kribis, Marat; Bucklin, Molly L.; Kumar, Dinesh Babu Uthaya; Tyler, Paul M.; Alam, Faiad; Jones, Kate M.; Sheikha, Hassan; Konnikova, Liza; Lakhani, Saquib A.; Montgomery, Ruth R.; Catanzaro, Jason; Du, Hongqiang; Digiacomo, Daniel V.; Rothermel, Holly; Moran, Christopher J.; Fiedler, Karoline; Warner, Neil; Hoppenreijs, Esther P. A. H.; van der Made, Caspar I.; Hoischen, Alexander; Olbrich, Peter; Neth, Olaf; Rodriguez-Martinez, Alejandro; Lucena Soto, Jose Manuel; van Rossum, Annemarie M. C.; Dalm, Virgil A. S. H.; Muise, Aleixo M.; Lucas, Carrie L."

作者地址："[Olyha, Sam J.; Bucklin, Molly L.; Kumar, Dinesh Babu Uthaya; Tyler, Paul M.; Alam, Faiad; Jones, Kate M.; Sheikha, Hassan; Lucas, Carrie L.] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA; [O'Connor, Shannon K.; Sheikha, Hassan; Konnikova, Liza; Lakhani, Saquib A.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT USA; [O'Connor, Shannon K.] Cincinnati Childrens Hosp Med Ctr, Div Rheumatol, Cincinnati, OH USA; [Kribis, Marat; Montgomery, Ruth R.] Yale Sch Med, Dept Internal Med, Sect Rheumatol, New Haven, CT USA; [Konnikova, Liza] Yale Univ, Sch Med, Div Neonatal & Perinatal Med, New Haven, CT USA; [Konnikova, Liza] Yale Med Sch, Dept Obstet Gynecol & Reprod Sci, New Haven, CT USA; [Konnikova, Liza; Lucas, Carrie L.] Yale Univ, Program Human & Translat Immunol, Sch Med, New Haven, CT 06510 USA; [Lakhani, Saquib A.] Yale Univ, Pediat Genom Discovery Program, Sch Med, New Haven, CT USA; [Catanzaro, Jason] Div Pediat Allergy & Clin Immunol, Natl Jewish Hlth, Denver, CO USA; [Du, Hongqiang] Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Childrens Hosp, Chongqing, Peoples R China; [Du, Hongqiang] Chongqing Med Univ, Minist Educ, Key Lab Child Dev & Disorders, Childrens Hosp, Chongqing, Peoples R China; [Du, Hongqiang] Chongqing Med Univ, Chongqing Key Lab Child Infect & Immun, Childrens Hosp, Chongqing, Peoples R China; [Du, Hongqiang] Chongqing Med Univ, Dept Rheumatol & Immunol, Childrens Hosp, Chongqing, Peoples R China; [Digiacomo, Daniel V.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA USA; [Rothermel, Holly] MassGen Children, MassGeneral Children, Boston, MA USA; [Moran, Christopher J.] MassGen Children, MassGeneral Children, Boston, MA USA; [Fiedler, Karoline; Muise, Aleixo M.] Hosp Sick Children, SickKids Inflammatory Bowel Dis Ctr, Toronto, ON, Canada; [Fiedler, Karoline; Warner, Neil; Muise, Aleixo M.] Hosp Sick Children, Res Inst, Cell Biol Program, Toronto, ON, Canada; [Hoppenreijs, Esther P. A. H.] Radboud Univ Nijmegen, Amalia Childrens Hosp, Dept Pediat Rheumatol, Med Ctr, Nijmegen, Netherlands; [van der Made, Caspar I.; Hoischen, Alexander] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, Nijmegen, Netherlands; [van der Made, Caspar I.; Hoischen, Alexander] Radboud Univ Nijmegen, Radboud Ctr Infect Dis, Med Ctr, Nijmegen, Netherlands; [Olbrich, Peter; Neth, Olaf] Biomed Inst Sevilla IBiS, Inborn Errors Immun Grp, CSIC, Seville, Spain; [Olbrich, Peter; Neth, Olaf] Hosp Univ Virgen del Rocio, Rheumatol & Immunol Unit, Pediat Infect Dis, Seville, Spain; [Olbrich, Peter] Univ Seville, Dept Farmacol Pediat & Radiol, Seville, Spain; [Rodriguez-Martinez, Alejandro] Hosp Univ Virgen del Rocio, Hepatol & Nutr Unit, Pediat Gastroenterol, Seville, Spain; [Lucena Soto, Jose Manuel] Hosp Univ Virgen del Rocio, Unidad Inmunol, Seville, Spain; [van Rossum, Annemarie M. C.] Univ Med Ctr, Sophia Childrens Hosp, Dept Pediat, Div Infect Dis & Immunol,Erasmus MC, Rotterdam, Netherlands; [van Rossum, Annemarie M. C.] Univ Med Ctr, Erasmus MC, Dept Med Microbiol & Infect Dis, Rotterdam, Netherlands; [Dalm, Virgil A. S. H.] Erasmus MC, Dept Immunol, Lab Med Immunol, Rotterdam, Netherlands; [Dalm, Virgil A. S. H.] Erasmus MC, Dept Internal Med, Div Allergy & Clin Immunol, Rotterdam, Netherlands; [Dalm, Virgil A. S. H.] Erasmus MC, Acad Ctr Rare Immunol Dis RIDC, Rotterdam, Netherlands; [Muise, Aleixo M.] Univ Toronto, Hosp Sick Children, Inst Med Sci & Biochem, Dept Pediat, Toronto, ON, Canada"

通信作者："Lucas, CL (通讯作者)，Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA.; Lucas, CL (通讯作者)，Yale Univ, Program Human & Translat Immunol, Sch Med, New Haven, CT 06510 USA."

来源：JOURNAL OF CLINICAL IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:001144087100002

JCR分区：Q1

影响因子：9.1

年份：2024

卷号：44

期号：2

开始页：　

结束页：　

文献类型：Article

关键词：Deficiency in ELF4 X-linked; DEX; Inborn error of immunity; Inflammatory bowel disease; Behcet's disease; Inflammation; ELF4

摘要："Defining monogenic drivers of autoinflammatory syndromes elucidates mechanisms of disease in patients with these inborn errors of immunity and can facilitate targeted therapeutic interventions. Here, we describe a cohort of patients with a Behcet's- and inflammatory bowel disease (IBD)-like disorder termed ""deficiency in ELF4, X-linked"" (DEX) affecting males with loss-of-function variants in the ELF4 transcription factor gene located on the X chromosome. An international cohort of fourteen DEX patients was assessed to identify unifying clinical manifestations and diagnostic criteria as well as collate findings informing therapeutic responses. DEX patients exhibit a heterogeneous clinical phenotype including weight loss, oral and gastrointestinal aphthous ulcers, fevers, skin inflammation, gastrointestinal symptoms, arthritis, arthralgia, and myalgia, with findings of increased inflammatory markers, anemia, neutrophilic leukocytosis, thrombocytosis, intermittently low natural killer and class-switched memory B cells, and increased inflammatory cytokines in the serum. Patients have been predominantly treated with anti-inflammatory agents, with the majority of DEX patients treated with biologics targeting TNF alpha."

基金机构：G. Harold and Leila Y. Mathers Charitable Foundation; Yale Cancer Center

基金资助正文："The authors thank the patients and their families for participation in research and all clinical care staff for their contributions. We acknowledge the Yale Cancer Center for support. Figs. 1A, 1B, and 3 were created with BioRender.com."