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Two rare UNC93B1 variants contribute to childhood-onset lupus

This work identifies two rare genetic variants of UNC93B1 that contribute to the development of childhood-onset lupus. Mice that expressed one of these variants developed a lupus-like disease. UNC93B1 is known to regulate the localization of Toll-like receptors (TLRs) to the endosome, and UNC93B1 variants resulted in enhanced responses to TLR7 and TLR8 agonists.

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Fig. 1: UNC93B1 variants lead to increased TLR7 responses in patient-derived peripheral blood mononuclear cells and lupus-like pathology in mice.

References

  1. Shen, N. et al. Sex-specific association of X-linked Toll-like receptor 7 (TLR7) with male systemic lupus erythematosus. Proc. Natl Acad. Sci. USA 107, 15838–15843 (2010). A research article providing initial evidence for the association of a common polymorphism in TLR7 with lupus.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Brown, G. J. et al. TLR7 gain-of-function genetic variation causes human lupus. Nature 605, 349–356 (2022). A research article that reports monogenic rare variants in TLR7 causing childhood-onset lupus in humans and a similar disease in mice.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Kim, Y. M., Brinkmann, M. M., Paquet, M. E. & Ploegh, H. L. UNC93B1 delivers nucleotide-sensing toll-like receptors to endolysosomes. Nature 452, 234–238 (2008). A study that revealed the role of UNC93B1 in TLR trafficking.

    Article  CAS  PubMed  Google Scholar 

  4. Su, L.-C., Xu, W.-D. & Huang, A.-F. IRAK family in inflammatory autoimmune diseases. Autoimmun. Rev. 3, 102461 (2020). A review article that discusses inhibition of IRAK1 and IRAK4 for the treatment of lupus-like conditions.

    Article  Google Scholar 

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This is a summary of: Al-Azab, M. et al. Genetic variants in UNC93B1 predispose to childhood-onset systemic lupus erythematosus. Nat. Immunol. https://doi.org/10.1038/s41590-024-01846-5 (2024).

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Two rare UNC93B1 variants contribute to childhood-onset lupus. Nat Immunol 25, 951–952 (2024). https://doi.org/10.1038/s41590-024-01850-9

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