Mendelian randomization study on causal association of FAM210B with drug-induced lupus

Xu, Yaqi; Gao, Ran; Zhang, Min; Zeng, Qi; Zhou, Shan; Zhu, Gaizhi; Su, Wenting; Wang, Renxi

doi:10.1007/s10067-024-06903-w

Cited by 1 publication

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“…Two recent bioinformatics studies have suggested that Fam210b is an important candidate for the classification and therapeutic targeting of SLE [16,17]. To prove the role of Fam210b in SLE via experimental methods, we constructed mice with Fam210b knockout and found that Fam210b knockout leads to a low probability of lupus-like symptoms in mice.…”

Section: Introductionmentioning

confidence: 99%

Deletion of the Mitochondrial Membrane Protein Fam210b Is Associated with the Development of Systemic Lupus Erythematosus

Xu,

Gao,

Zhang

et al. 2024

IJMS

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Mitochondrial dysfunction has been increasingly recognized as a trigger for systemic lupus erythematosus (SLE). Recent bioinformatics studies have suggested Fam210b as a significant candidate for the classification and therapeutic targeting of SLE. To experimentally prove the role of Fam210b in SLE, we constructed Fam210b knockout (Fam210b−/−) mice using the CRISPR-Cas9 method. We found that approximately 15.68% of Fam210b−/− mice spontaneously developed lupus-like autoimmunity, which was characterized by skin ulcerations, splenomegaly, and an increase in anti-double-stranded DNA (anti-dsDNA) IgG antibodies and anti-nuclear antibodies(ANA). Single-cell sequencing showed that Fam210b was mainly expressed in erythroid cells. Critically, the knockout of Fam210b resulted in abnormal erythrocyte differentiation and development in the spleens of mice. Concurrently, the spleens exhibited an increased number of CD71+ erythroid cells, along with elevated levels of reactive oxygen species (ROS) in the erythrocytes. The co-culture of CD71+ erythroid cells and lymphocytes resulted in lymphocyte activation and promoted dsDNA and IgG production. In summary, Fam210b knockout leads to a low probability of lupus-like symptoms in mice through the overproduction of ROS in CD71+ erythroid cells. Thus, Fam210b reduction may serve as a novel key marker that triggers the development of SLE.

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Section: Introductionmentioning

confidence: 99%