A de novo TLR7 gain-of-function mutation causing severe monogenic lupus in an infant
Jarmila Stremenova Spegarova, Praisoody Sinnappurajar, Dalila Al Julandani, Rokas Navickas, Helen Griffin, Manisha Ahuja, Angela Grainger, Katie Livingstone, Gillian I. Rice, Fraser Sutherland, Corinne Hayes, Simon Parke, Lewis Pang, Marion R. Roderick, Mary Slatter, Yanick Crow, Athimalaipet V. Ramanan, Sophie Hambleton
Jarmila Stremenova Spegarova, Praisoody Sinnappurajar, Dalila Al Julandani, Rokas Navickas, Helen Griffin, Manisha Ahuja, Angela Grainger, Katie Livingstone, Gillian I. Rice, Fraser Sutherland, Corinne Hayes, Simon Parke, Lewis Pang, Marion R. Roderick, Mary Slatter, Yanick Crow, Athimalaipet V. Ramanan, Sophie Hambleton
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Research Letter Autoimmunity Immunology

A de novo TLR7 gain-of-function mutation causing severe monogenic lupus in an infant

Abstract

Authors

Jarmila Stremenova Spegarova, Praisoody Sinnappurajar, Dalila Al Julandani, Rokas Navickas, Helen Griffin, Manisha Ahuja, Angela Grainger, Katie Livingstone, Gillian I. Rice, Fraser Sutherland, Corinne Hayes, Simon Parke, Lewis Pang, Marion R. Roderick, Mary Slatter, Yanick Crow, Athimalaipet V. Ramanan, Sophie Hambleton

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Figure 1

TLR7 gain-of-function mutation in a young child with severe SLE.

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TLR7 gain-of-function mutation in a young child with severe SLE. (A) Per...
(A) Persistently pathologically elevated interferon-stimulated gene and (B) neutrophil signature gene transcripts in patient at indicated time points. The y axis shows transcript abundance in arbitrary units (relative quantification [RQ] values) for indicated genes. (C) Pedigree. (D) Capillary sequencing of PCR amplicons. P, proline substituted by L, leucine. (E) Increased transcription of proinflammatory cytokines TNF-α, IL-1b, and IL-6 in patient PBMCs stimulated with TLR7/8 ligand CL097 or polyI:C. US, unstimulated. (F) Increased TLR7 protein expression in patient PBMC subsets quantitated by (G) flow cytometry. Representative of 2 independent experiments. (H) TLR7 protein expression detected by immunoblotting of transfected HEK293T cells 48 hours after transfection. (I) NF-κB activity by dual luciferase assay after TLR7 plasmid transfection into HEK293T cells and treatment with indicated TLR7 ligands. Luminescence signal normalized to unstimulated cells from 4 independent experiments. Two-way ANOVA, **P < 0.01, ****P < 0.0001. Data represent mean ± SD.