Immunodeficiency and bone marrow failure with mosaic and germline TLR8 gain of function

Authors

• Jahnavi Aluri, Division of Rheumatology/Immunology
• Alicia Bach, Division of Hematology/Oncology, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO
• Saara Kaviany, Pediatric Hematology Oncology, Vanderbilt University Medical Center, Nashville, TN
• Luana Chiquetto Paracatu, Division of Hematology/Oncology, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO
• Maleewan Kitcharoensakkul, Division of Rheumatology/Immunology; Division of Allergy and Pulmonary Medicine, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO
• Magdalena A. Walkiewicz, Centralized Sequencing Initiative, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
• Christopher D. Putnam, Department of Medicine, University of California School of Medicine, San Diego, La Jolla, CA; San Diego Branch, Ludwig Institute for Cancer Research, La Jolla, CA
• Marwan Shinawi, Division of Genetics and Genomic Medicine, Department of Pediatrics
• Nermina Saucier, Division of Rheumatology/Immunology
• Elise M. Rizzi, Division of Allergy and Immunology, Department of Medicine, Washington University School of Medicine, St. Louis, MO
• Michael T. Harmon, Division of Rheumatology/Immunology
• Molly P. Keppel, Division of Rheumatology/Immunology
• Michelle Ritter, Division of Rheumatology/Immunology
• Morgan Similuk, Centralized Sequencing Initiative, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
• Elaine Kulm, Clinical Research Directorate, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, Frederick, MD
• Michael Joyce, Nemours Children's Specialty Care, Jacksonville, FL
• Adriana A. de Jesus, Translational Autoinflammatory Diseases Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
• Raphaela Goldbach-Mansky, Translational Autoinflammatory Diseases Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
• Yi-Shan Lee, Division of Anatomic and Molecular Pathology
• Marina Cella, Division of Immunology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO
• Peggy L. Kendall, Division of Allergy and Immunology, Department of Medicine, Washington University School of Medicine, St. Louis, MO; Division of Immunology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO
• Mary C. Dinauer, Division of Hematology/Oncology, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO
• Jeffrey J. Bednarski, Division of Hematology/Oncology, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO
• Christina Bemrich-Stolz, Division of Hematology and Oncology, Department of Pediatrics, University of Alabama School of Medicine, Birmingham, AL
• Scott W. Canna, Division of Pediatric Rheumatology and RK Mellon Institute, Department of Pediatrics, UPMC Children's Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, PA
• Shirley M. Abraham, Division of Hematology and Oncology, Department of Pediatrics, University of New Mexico, Albuquerque, NM
• Matthew M. Demczko, Division of Diagnostic Referral
• Jonathan Powell, Division of Pediatric Hematology/Oncology, Department of Pediatrics, Nemours Alfred I. DuPont Hospital for Children, Wilmington, DE
• Stacie M. Jones, Division of Allergy and Immunology, Department of Pediatrics, University of Arkansas for Medical Sciences and Arkansas Children's Hospital, Little Rock, AR
• Amy M. Scurlock, Division of Allergy and Immunology, Department of Pediatrics, University of Arkansas for Medical Sciences and Arkansas Children's Hospital, Little Rock, AR
• Suk See De Ravin, Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
• Jack J. Bleesing, Division of Bone Marrow Transplantation and Immunodeficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
• James A. Connelly, Pediatric Hematology Oncology, Vanderbilt University Medical Center, Nashville, TN
• V Koneti Rao, Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
• Laura G. Schuettpelz, Division of Hematology/Oncology, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO
• Megan A. Cooper, Division of Rheumatology/Immunology

Document Type

Article

Publication Date

5-6-2021

Abstract

Inborn errors of immunity (IEI) are a genetically heterogeneous group of disorders with a broad clinical spectrum. Identification of molecular and functional bases of these disorders is important for diagnosis, treatment, and an understanding of the human immune response. We identified 6 unrelated males with neutropenia, infections, lymphoproliferation, humoral immune defects, and in some cases bone marrow failure associated with 3 different variants in the X-linked gene TLR8, encoding the endosomal Toll-like receptor 8 (TLR8). Interestingly, 5 patients had somatic variants in TLR8 with

Publisher

American Society of Hematology

Publication Title

Blood

ISSN

1528-0020

Volume

137

Issue

18

First Page

2450

Last Page

2462

Recommended Citation

Aluri J, Bach A, Kaviany S, Chiquetto Paracatu L, Kitcharoensakkul M, Walkiewicz MA, Putnam CD, Shinawi M, Saucier N, Rizzi EM, Harmon MT, Keppel MP, Ritter M, Similuk M, Kulm E, Joyce M, de Jesus AA, Goldbach-Mansky R, Lee YS, Cella M, Kendall PL, Dinauer MC, Bednarski JJ, Bemrich-Stolz C, Canna SW, Abraham SM, Demczko MM, Powell J, Jones SM, Scurlock AM, De Ravin SS, Bleesing JJ, Connelly JA, Rao VK, Schuettpelz LG, Cooper MA. Immunodeficiency and bone marrow failure with mosaic and germline TLR8 gain of function. Blood. 2021 May 6;137(18):2450-2462. doi: 10.1182/blood.2020009620. PMID: 33512449; PMCID: PMC8109013.