Details

Autor(en) / Beteiligte

• Sinthuwiwat, Thivaratana
• Buranapraditkun, Supranee
• Kamolvisit, Wuttichart
• Tongkobpetch, Siraprapa
• Chetruengchai, Wanna
• Srichomthong, Chalurmpon
• Assawapitaksakul, Adjima
• Phokaew, Chureerat
• Kueanjinda, Patipark
• Palaga, Tanapat
• Boonpiyathad, Tadech
• Suphapeetiporn, Kanya
• Hirankarn, Nattiya
• Shotelersuk, Vorasuk

Titel

A LILRB1 variant with a decreased ability to phosphorylate SHP-1 leads to autoimmune diseases

Ist Teil von

• Scientific reports, 2022-09, Vol.12 (1), p.15420-15420, Article 15420

Ort / Verlag

London: Nature Publishing Group

Erscheinungsjahr

2022

Quelle

EZB Free E-Journals

Beschreibungen/Notizen

• Abstract Inborn errors of immunity are known to cause not only immunodeficiencies and allergies but also autoimmunity. Leukocyte immunoglobulin-like receptor B1 (LILRB1) is a receptor on leukocytes playing a role in regulating immune responses. No phenotypes have been reported to be caused by germline mutations in LILRB1 . We aimed to identify the causative variant in a three-generation family with nine members suffering from one of the three autoimmune diseases—Graves’ disease, Hashimoto's thyroiditis, or systemic lupus erythematosus. Whole-genome linkage study revealed a locus on chromosome 19q13.4 with the maximum LOD score of 2.71. Whole-exome sequencing identified a heterozygous missense variant, c.479G > A (p. G160E) in LILRB1 , located within the chromosomal-linked region, in all nine affected members. The variant has never been previously reported. Jurkat cells transfected with the mutant LILRB1 , compared with those with the wild-type LILRB1 , showed decreased phosphorylation of both LILRB1 and its downstream protein, SHP-1. Flow cytometry was used to study immunophenotype and revealed that LILRB1 was significantly lower on the surface of activated regulatory T lymphocytes (Treg) cells of patients. Single-cell RNA sequencing showed substantially increased M1-like monocytes in peripheral blood mononuclear cells of affected individuals. This study, for the first time, implicates LILRB1 as a new disease gene for autoimmunity.