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Human inherited PD-L1 deficiency is clinically and immunologically less severe than PD-1 deficiency

Journal Of Experimental Medicine. 2024-04; 
Matthew B Johnson, Masato Ogishi, Clara Domingo-Vila, Elisa De Franco, Matthew N Wakeling, Zineb Imane, Brittany Resnick, Evangelia Williams, Rui Pedro Galão, Richard Caswell, James Russ-Silsby, Yoann Seeleuthner , Darawan Rinchai, Iris Fagniez, Basilin Benson, Matthew J Dufort, Cate Speake , Megan E Smithmyer, Michelle Hudson, Rebecca Dobbs; EXE-T1D consortium; Zoe Quandt, Andrew T Hattersley ,Peng Zhang, Stephanie Boisson-Dupuis , Mark S Anderson, Jean-Laurent Casanova, Timothy I Tree, Richard A Oram
Products/Services Used Details Operation
Catalog Antibody For the PD-1:PD-L1 blockade assay, the following mAbs were added at a final concentration of 5 μg/ml: anti-PD1 mouse IgG1 (Cat: A01829, Clone: PD1.D3; GenScript), mouse IgG1 isotype control (Cat: MAB002, Clone: #11711; R&D), anti-PD-L1 human IgG1 (N298A) (Cat: hpdl1-mab12; InvivoGen, equivalent to atezolizumab), and human IgG1 isotype control (N298A) (Cat: bgal-mab12; InvivoGen) Get A Quote

摘要

We previously reported two siblings with inherited PD-1 deficiency who died from autoimmune pneumonitis at 3 and 11 years of age after developing other autoimmune manifestations, including type 1 diabetes (T1D). We report here two siblings, aged 10 and 11 years, with neonatal-onset T1D (diagnosed at the ages of 1 day and 7 wk), who are homozygous for a splice-site variant of CD274 (encoding PD-L1). This variant results in the exclusive expression of an alternative, loss-of-function PD-L1 protein isoform in overexpression experiments and in the patients' primary leukocytes. Surprisingly, cytometric immunophenotyping and single-cell RNA sequencing analysis on blood leukocytes showed largely normal development and... More

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