Toll-like receptor 3 (TLR3) variant and NLRP12 mutation confer susceptibility to a complex clinical presentation

Yuval Tal; Yaarit Ribak; Aya Khalaila; Oded Shamriz; Nofar Marcus; Adar Zinger; Vardiella Meiner; Ronen Schuster; Eli C Lewis; Amit Nahum

doi:10.1016/j.clim.2019.108249

Toll-like receptor 3 (TLR3) variant and NLRP12 mutation confer susceptibility to a complex clinical presentation

Clin Immunol. 2020 Mar:212:108249. doi: 10.1016/j.clim.2019.108249. Epub 2019 Aug 21.

Authors

Yuval Tal¹, Yaarit Ribak², Aya Khalaila³, Oded Shamriz⁴, Nofar Marcus⁵, Adar Zinger⁶, Vardiella Meiner⁷, Ronen Schuster⁸, Eli C Lewis⁸, Amit Nahum³

Affiliations

¹ Allergy and Clinical immunology Unit, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; Internal Medicine Division, Hadassah-Hebrew University Medical Center, Ein Kerem, Jerusalem, Israel. Electronic address: yuvalt@hadassah.org.il.
² Allergy and Clinical immunology Unit, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; Internal Medicine Division, Hadassah-Hebrew University Medical Center, Ein Kerem, Jerusalem, Israel.
³ Pediatrics Department A, Soroka University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
⁴ Allergy and Clinical immunology Unit, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; The Lautenberg Center for Immunology and Cancer Research, Institute of Medical Research Israel-Canada, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
⁵ Department of Pediatrics B, Schneider Children's Medical Center of Israel, Petah Tiqva, Israel.
⁶ The Lautenberg Center for Immunology and Cancer Research, Institute of Medical Research Israel-Canada, Hebrew University-Hadassah Medical School, Jerusalem, Israel; Institute of Gastroenterology and Liver Diseases, Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
⁷ Department of Human Genetics and Metabolic Diseases, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
⁸ Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.

PMID: 31445170
DOI: 10.1016/j.clim.2019.108249

Abstract

Genetic aberrations in the toll-like receptor (TLR)3 pathway are associated with increased susceptibility to herpes simplex virus (HSV) infections. Leucine-rich repeat and PYD-containing protein (NLRP)12 is a component of the inflammasome apparatus, which is critical to an immediate innate inflammatory response. Aberrations in NLRP12 have been shown to mediate auto-inflammation. In this study, we present a 44-year old patient with severe HSV esophagitis and Crohn's disease. An immune and genetic investigation confirmed two coinciding genetic mutations in TLR3 and NLRP12. Our findings support conducting laboratory workup that targets TLR3 pathway in the immunocompetent host developing recurrent HSV infections.

Keywords: Autoinflammation; Crohn's disease; Herpes simplex esophagitis; Herpes simplex virus (HSV); Leucine-rich repeat and PYD-containing protein (NLRP12); NACHT domain; NLRP12; TLR3; Toll-like receptor.

Publication types

Case Reports

MeSH terms

Acyclovir / therapeutic use
Adult
Antibodies, Monoclonal, Humanized / therapeutic use
Antiviral Agents / therapeutic use
Crohn Disease / drug therapy
Crohn Disease / genetics*
Crohn Disease / immunology
Esophagitis / genetics*
Esophagitis / immunology
Esophagitis / virology
Female
Gastrointestinal Agents / therapeutic use
Herpes Simplex / drug therapy
Herpes Simplex / genetics*
Herpes Simplex / immunology
Herpes Simplex / prevention & control
Humans
Intracellular Signaling Peptides and Proteins / genetics*
Intracellular Signaling Peptides and Proteins / immunology
Mutation
Signal Transduction
Toll-Like Receptor 3 / genetics*
Toll-Like Receptor 3 / immunology
Valganciclovir / therapeutic use
Whole Genome Sequencing

Substances

Antibodies, Monoclonal, Humanized
Antiviral Agents
Gastrointestinal Agents
Intracellular Signaling Peptides and Proteins
NLRP12 protein, human
TLR3 protein, human
Toll-Like Receptor 3
vedolizumab
Valganciclovir
Acyclovir