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TMEM176B is co-expressed with TMEM176A and upregulated in peripheral blood monocytes of patients with primary Sjögren's syndrome.

Yuan Yuan·Hanxi Luo·Bohao Yang·Xiaoyu Yu·Ziqi Xiong·Yiming Gao·Chen Liu·Pingzhang Wang
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Abstract

OBJECTIVES: This study aims to determine the role of acid‑sensitive nonspecific cation channels transmembrane protein 176A (TMEM176A) and TMEM176B in autoimmune diseases, with a focus on primary Sjögren's Syndrome (pSS). METHODS: We examined the expression patterns of TMEM176A and TMEM176B across tissues and cells utilizing bulk RNA-seq and scRNA-seq datasets. Immunophenotyping analysis was performed by flow cytometry to compare CD62L expression between TMEM176B⁺ and TMEM176B⁻ monocytes. The proportion of TMEM176B+ cells in monocytes was interrogated in both pSS patients and healthy controls. Clinical correlations of TMEM176B with anti‑SSB antibody and complement C4 levels were also evaluated. RESULTS: TMEM176A and TMEM176B showed conserved co‑expression and were significantly upregulated in autoimmune diseases. TMEM176B⁺ monocytes displayed higher CD62L positivity rate than TMEM176B- monocytes. In pSS patients, the proportion of TMEM176B⁺ monocytes was elevated in total monocytes, classical monocytes (cMo) and intermediate monocytes (iMo). The proportion of TMEM176B+ monocytes positively correlated with anti‑SSB levels, while several TMEM176B-associated monocyte subset markers inversely correlated with C4. CONCLUSION: TMEM176A and TMEM176B are highly correlated. TMEM176B expression in monocytes is linked to pSS and may serve as a novel auxiliary diagnostic biomarker.

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HumansSjogren's SyndromeMembrane ProteinsMonocytesUp-RegulationFemaleMiddle AgedMaleAdultFlow CytometryAgedImmunophenotypingL-SelectinCase-Control StudiesAntibodies, AntinuclearCD54CD62LTMEM176Bautoimmune diseaseprimary Sjögren’s syndromeJournal ArticleResearch Support, Non-U.S. Gov't

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Yuan Yuan, Hanxi Luo, Bohao Yang, Xiaoyu Yu, Ziqi Xiong, Yiming Gao, Chen Liu, Pingzhang Wang. 2026-09-01. TMEM176B is co-expressed with TMEM176A and upregulated in peripheral blood monocytes of patients with primary Sjögren's syndrome.. https://doi.org/10.1093/rheumatology%2Fkeag431

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