Expression and significance of <i>ERdj5</i> and <i>XBP1</i> in primary Sjögren syndrome_West China Medical Journal

Authors：

FAN Jiamei ^1,2 , LI Jinhui ³ , XIE Youbang ⁴ ,  LI Wenqian ⁴

1. Sichuan Jinyu Medical Laboratory Center Co., LTD, Chengdu, Sichuan 610066, P. R. China;
2. Graduate School of Qinghai University, Xining, Qinghai 810016, P. R. China;
3. Chengdu BOE Hospital, Chengdu, Sichuan 610200, P. R. China;
4. Department of Hematology and Rheumatology, Qinghai Provincial People’s Hospital, Xining, Qinghai 810007, P. R. China;

Corresponding author：

LI Wenqian, Email: lwq21616@163.com

Keywords：

Primary Sjögren syndrome; ERdj5; XBP1

DOI：

10.7507/1002-0179.202402074

Video：

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Objective To detect the expression levels of ERdj5 and XBP1 in the salivary glands of patients with primary Sjögren syndrome (pSS), and analyze the correlation of the expression levels of ERdj5 and XBP1 with salivary gland damage and oral symptoms to explore their significance in the pathogenesis of pSS. Methods A total of 60 pSS patients in the departments of rheumatology and immunology of Xi’an Honghui Hospital and Qinghai Provincial People’s Hospital between January 2020 and June 2021were randomly selected as the case group, and 20 healthy participants in Qinghai Provincial People’s Hospital in the same period were randomly selected as the control group. The mRNA and protein expression levels of ERdj5 and XBP1 in salivary gland tissues were detected by reverse transcription-polymerase chain reaction and Western blot, respectively, and their correlation with histopathology, salivary flow rate, dry mouth degree, and clinical test indicators were analyzed. Results The mRNA and protein expression levels of ERdj5 and XBP1 in the case group were higher than those in the control group (P<0.001). The ERdj5 mRNA expression was positively correlated with the XBP1 mRNA expression in the case group (r_s=0.936, P<0.001). The expression levels of ERdj5 mRNA and XBP1 mRNA in the case group were positively correlated with the pathological grade of labial gland (r_s=0.344, P<0.001; r_s=0.401, P<0.001), dry mouth degree (r_s=0.683, P<0.001; r_s=0.730, P<0.001), anti-Ro/SSA antibody (r_s=0.363, P<0.001; r_s=0.350, P<0.001), anti-La/SSB antibody (r_s=0.506, P<0.001; r_s=0.471, P<0.001), and European League Against Rheumatism Sjogren’s Syndrome Disease Activity Index (r_s=0.782, P<0.001; r_s=0.865, P<0.001), and were negatively correlated with salivary flow rate (r_s=–0.445, P<0.001; r_s=–0.526, P<0.001). Conclusion The expression levels of ERdj5 and XBP1 in salivary glands are increased in pSS patients, and they are related to disease activity, anti-Ro/SSA and anti-La/SSB autoantibodies, damage degree of salivary gland and oral symptoms of patients.

Citation： FAN Jiamei, LI Jinhui, XIE Youbang, LI Wenqian. Expression and significance of ERdj5 and XBP1 in primary Sjögren syndrome. West China Medical Journal, 2024, 39(4): 594-598. doi: 10.7507/1002-0179.202402074 Copy

1.	Papageorgiou A, Voulgarelis M, Tzioufas AG. Clinical picture, outcome and predictive factors of lymphoma in Sjögren syndrome. Autoimmun Rev, 2015, 14(7): 641-649.
2.	Donnelly SM, Sheahan BJ, Atkins GJ. Long-term effects of Semliki Forest virus infection in the mouse central nervous system. Neuropathol Appl Neurobiol, 1997, 23(3): 235-241.
3.	Katsiougiannis S, Tenta R, Skopouli FN. Autoimmune epithelitis (Sjögren’s syndrome); the impact of metabolic status of glandular epithelial cells on auto-immunogenicity. J Autoimmun, 2019, 104: 102335.
4.	邬珊珊, 廉姜芳. 内质网应激相关分子伴侣 Bip 及辅助伴侣 ERdjs. 生命的化学, 2020, 40(10): 1787-1791.
5.	张霞丽, 万福生. X-盒结合蛋白 1 的病理生理学作用//华东六省一市生物化学与分子生物学会 2010 年学术交流会. 南昌: 中国生物化学与分子生物学会, 2010: 39.
6.	郭思维, 于雯, 王煦, 等. XBP1 在小鼠早期妊娠子宫的表达和调节. 生理学报, 2021, 73(2): 208-216.
7.	张文, 厉小梅, 徐东, 等. 原发性干燥综合征诊疗规范. 中华内科杂志, 2020(4): 269-270.
8.	夏萍, 张梅兮, 穆森, 等. 舍格伦综合征患者唾液 MMP-9 表达与组织病理分级相关性研究. 口腔医学研究, 2017, 33(12): 1302-1305.
9.	Kroese FGM, Haacke EA, Bombardieri M. The role of salivary gland histopathology in primary Sjögren’s syndrome: promises and pitfalls. Clin Exp Rheumatol, 2018, 36(3 Suppl 112): 222-233.
10.	刘丽, 李延萍, 吴斌, 等. 涎腺超声在原发性干燥综合征中的应用价值. 中国现代医生, 2021, 59(1): 175-180.
11.	Campos J, Hillen MR, Barone F. Salivary gland pathology in Sjögren’s syndrome. Rheum Dis Clin North Am, 2016, 42(3): 473-483.
12.	Torchia D, Happle R. Phacomatosis spilosebacea: a new name for a distinctive binary genodermatosis. J Am Acad Dermatol, 2023, 89(4): 764-773.
13.	梅永君, 李志军. 干燥综合征的诊断与治疗. 中华全科医学, 2020, 18(6): 890-891.
14.	Okuma A, Hoshino K, Ohba T, et al. Enhanced apoptosis by disruption of the STAT3-IκB-ζ signaling pathway in epithelial cells induces Sjögren’s syndrome-like autoimmune disease. Immunity, 2013, 38(3): 450-460.
15.	Corrigendum. Expert Rev Clin Immunol, 2017, 13(5): 507.
16.	Hosoda A, Tokuda M, Akai R, et al. Positive contribution of ERdj5/JPDI to endoplasmic reticulum protein quality control in the salivary gland. Biochem J, 2009, 425(1): 117-125.
17.	Apostolou E, Moustardas P, Iwawaki T, et al. Ablation of the chaperone protein ERdj5 results in a Sjögren’s syndrome-like phenotype in mice, consistent with an upregulated unfolded protein response in human patients. Front Immunol, 2019, 10: 506.
18.	Moustardas P, Yamada-Fowler N, Apostolou E, et al. Deregulation of the kallikrein protease family in the salivary glands of the Sjögren’s syndrome ERdj5 knockout mouse model. Front Immunol, 2021, 12: 69391.
19.	Kim S, Joe Y, Kim HJ, et al. Endoplasmic reticulum stress-induced IRE1α activation mediates cross-talk of GSK-3β and XBP-1 to regulate inflammatory cytokine production. J Immunol, 2015, 194(9): 4498-4506.
20.	Kyriakidis NC, Kapsogeorgou EK, Tzioufas AG. A comprehensive review of autoantibodies in primary Sjögren’s syndrome: clinical phenotypes and regulatory mechanisms. J Autoimmun, 2014, 51: 67-74.
21.	Choi HJ, Tang CA, Tian L, et al. XBP-1s promotes B cell pathogenicity in chronic GVHD by restraining the activity of regulated IRE-1α-dependent decay. Front Immunol, 2021, 12: 705484.

1. Papageorgiou A, Voulgarelis M, Tzioufas AG. Clinical picture, outcome and predictive factors of lymphoma in Sjögren syndrome. Autoimmun Rev, 2015, 14(7): 641-649.
2. Donnelly SM, Sheahan BJ, Atkins GJ. Long-term effects of Semliki Forest virus infection in the mouse central nervous system. Neuropathol Appl Neurobiol, 1997, 23(3): 235-241.
3. Katsiougiannis S, Tenta R, Skopouli FN. Autoimmune epithelitis (Sjögren’s syndrome); the impact of metabolic status of glandular epithelial cells on auto-immunogenicity. J Autoimmun, 2019, 104: 102335.
4. 邬珊珊, 廉姜芳. 内质网应激相关分子伴侣 Bip 及辅助伴侣 ERdjs. 生命的化学, 2020, 40(10): 1787-1791.
5. 张霞丽, 万福生. X-盒结合蛋白 1 的病理生理学作用//华东六省一市生物化学与分子生物学会 2010 年学术交流会. 南昌: 中国生物化学与分子生物学会, 2010: 39.
6. 郭思维, 于雯, 王煦, 等. XBP1 在小鼠早期妊娠子宫的表达和调节. 生理学报, 2021, 73(2): 208-216.
7. 张文, 厉小梅, 徐东, 等. 原发性干燥综合征诊疗规范. 中华内科杂志, 2020(4): 269-270.
8. 夏萍, 张梅兮, 穆森, 等. 舍格伦综合征患者唾液 MMP-9 表达与组织病理分级相关性研究. 口腔医学研究, 2017, 33(12): 1302-1305.
9. Kroese FGM, Haacke EA, Bombardieri M. The role of salivary gland histopathology in primary Sjögren’s syndrome: promises and pitfalls. Clin Exp Rheumatol, 2018, 36(3 Suppl 112): 222-233.
10. 刘丽, 李延萍, 吴斌, 等. 涎腺超声在原发性干燥综合征中的应用价值. 中国现代医生, 2021, 59(1): 175-180.
11. Campos J, Hillen MR, Barone F. Salivary gland pathology in Sjögren’s syndrome. Rheum Dis Clin North Am, 2016, 42(3): 473-483.
12. Torchia D, Happle R. Phacomatosis spilosebacea: a new name for a distinctive binary genodermatosis. J Am Acad Dermatol, 2023, 89(4): 764-773.
13. 梅永君, 李志军. 干燥综合征的诊断与治疗. 中华全科医学, 2020, 18(6): 890-891.
14. Okuma A, Hoshino K, Ohba T, et al. Enhanced apoptosis by disruption of the STAT3-IκB-ζ signaling pathway in epithelial cells induces Sjögren’s syndrome-like autoimmune disease. Immunity, 2013, 38(3): 450-460.
15. Corrigendum. Expert Rev Clin Immunol, 2017, 13(5): 507.
16. Hosoda A, Tokuda M, Akai R, et al. Positive contribution of ERdj5/JPDI to endoplasmic reticulum protein quality control in the salivary gland. Biochem J, 2009, 425(1): 117-125.
17. Apostolou E, Moustardas P, Iwawaki T, et al. Ablation of the chaperone protein ERdj5 results in a Sjögren’s syndrome-like phenotype in mice, consistent with an upregulated unfolded protein response in human patients. Front Immunol, 2019, 10: 506.
18. Moustardas P, Yamada-Fowler N, Apostolou E, et al. Deregulation of the kallikrein protease family in the salivary glands of the Sjögren’s syndrome ERdj5 knockout mouse model. Front Immunol, 2021, 12: 69391.
19. Kim S, Joe Y, Kim HJ, et al. Endoplasmic reticulum stress-induced IRE1α activation mediates cross-talk of GSK-3β and XBP-1 to regulate inflammatory cytokine production. J Immunol, 2015, 194(9): 4498-4506.
20. Kyriakidis NC, Kapsogeorgou EK, Tzioufas AG. A comprehensive review of autoantibodies in primary Sjögren’s syndrome: clinical phenotypes and regulatory mechanisms. J Autoimmun, 2014, 51: 67-74.
21. Choi HJ, Tang CA, Tian L, et al. XBP-1s promotes B cell pathogenicity in chronic GVHD by restraining the activity of regulated IRE-1α-dependent decay. Front Immunol, 2021, 12: 705484.

West China Medical Journal

Expression and significance of ERdj5 and XBP1 in primary Sjögren syndrome

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