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Case Reports
. 2024 May 16;134(13):e179193.
doi: 10.1172/JCI179193.

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

Jarmila Stremenova Spegarova  1 , Praisoody Sinnappurajar  2 , Dalila Al Julandani  2 , Rokas Navickas  1 , Helen Griffin  1 , Manisha Ahuja  1 , Angela Grainger  1 , Katie Livingstone  3 , Gillian I Rice  4 , Fraser Sutherland  3 , Corinne Hayes  5 , Simon Parke  5 , Lewis Pang  6 , Marion R Roderick  7   8 , Mary Slatter  9 , Yanick Crow  3 , Athimalaipet V Ramanan  2   8 , Sophie Hambleton  1   9
Affiliations
Case Reports

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

Jarmila Stremenova Spegarova et al. J Clin Invest. .
No abstract available

Keywords: Autoimmunity; Immunology; Lupus; Monogenic diseases; Stem cell transplantation.

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Conflict of interest statement

Conflict of interest: SH declares research funding from Pharming and has received honoraria for consultancy or teaching from Takeda, CSL Behring, Pharming, Hitachi Vantara, and Videregen.

Figures

Figure 1
Figure 1. TLR7 gain-of-function mutation in a young child with severe SLE.
(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.
See this image and copyright information in PMC

References

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