Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Oct 21;45(1):27.
doi: 10.1007/s10875-024-01824-4.

Refractory Autoimmune Thrombocytopenia in an Infant with a De Novo TLR7 Gain-of-Function Variant

Surabhi Menon #  1   2 , Diane Maurice #  3 , Lauren A Robinson #  4   5 , Joshua Milner  6 , Virginia Pascual  4 , Carola G Vinuesa #  7 , Shipra Kaicker #  8   9
Affiliations

Refractory Autoimmune Thrombocytopenia in an Infant with a De Novo TLR7 Gain-of-Function Variant

Surabhi Menon et al. J Clin Immunol. .
No abstract available

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosure: SK has received honoraria for consultancy from Pfizer, CSL Behring, and Octapharma; CGV: honoraria from BMS and Merck.

Figures

Figure 1
Figure 1. TLR7 G818V confers gain of TLR7 function.
A) Family tree of the patient presenting a heterozygous TLR-7G818V de novo variant. B) Sanger sequencing results show the de novo variant (G>T) identified in the proband (A.II 1). C) Conservation of G818. D) G818 amino acid localization of TLR7 in the 3D structure as predicted by Alpha Fold. E) NF-kB/AP-1 relative activity measured in the supernatant of HEK-BlueTM cells transfected with either no DNA, wild-type TLR7 or G181V TLR7 plasmids. Data are mean and s.d. for n=9 biological replicates or transfections shown as individual dots. Statistical significance (p<0.0001) was calculated using the unpaired t-test. F) Western blot showing relative abundance of the cleaved N-terminal fragment of TLR7 in PBMC lysates from the patient (ITP) and healthy control (HC) over GAPDH, images obtained using BioRad ChemiDoc imaging system and analysed using ImageJ2 software. G) Histograms showing MFI of ISG proteins ISG15 and CD169 (Siglec-1) in monocytes isolated from the patient (ITP) and a healthy control (HC); acquired on Cytek Aurora Cytometer and analysed using FlowJo Software.
See this image and copyright information in PMC

References

    1. Pisitkun P, Deane JA, Difilippantonio MJ, Tarasenko T, Satterthwaite AB, Bolland S. Autoreactive B Cell Responses to RNA-Related Antigens Due to TLR7 Gene Duplication. Science. 2006 Jun 16;312(5780):1669–72. - PubMed
    1. Brown GJ, Cañete PF, Wang H, Medhavy A, Bones J, Roco JA, et al. TLR7 gain-of-function genetic variation causes human lupus. Nature. 2022 May;605(7909):349–56. doi: 10.1038/s41586-022-04642-z. - DOI - PMC - PubMed
    1. David C, Badonyi M, Kechiche R, Insalaco A, Zecca M, De Benedetti F, et al. Interface Gain-of-Function Mutations in TLR7 Cause Systemic and Neuro-inflammatory Disease. J Clin Immunol. 2024 Feb 7;44(2):60. doi: 10.1007/s10875-024-01660-6. - DOI - PMC - PubMed
    1. Stremenova Spegarova J, Sinnappurajar P, Al Julandani D, Navickas R, Griffin H, Ahuja M, et al. A de novo TLR7 gain-of-function mutation causing severe monogenic lupus in an infant. J Clin Invest. 2024 May 16;:e179193. doi: 10.1172/JCI179193. - DOI - PMC - PubMed
    1. Soni C, Perez OA, Voss WN, Pucella JN, Serpas L, Mehl J, et al. Plasmacytoid Dendritic Cells and Type I Interferon Promote Extrafollicular B Cell Responses to Extracellular Self-DNA. Immunity. 2020 Jun 16;52(6):1022–1038.:e7. doi: 10.1016/j.immuni.2020.04.015. - DOI - PMC - PubMed

LinkOut - more resources