Expression and significance of <i>ERdj5</i> and <i>XBP1</i> in primary Sj?gren 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 Sj?gren 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 Sj?gren 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 Sj?gren 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 Sj?gren 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 (Sj?gren’s syndrome); the impact of metabolic status of glandular epithelial cells on auto-immunogenicity. J Autoimmun, 2019, 104: 102335.
4.	鄔珊珊, 廉姜芳. 內質網應激相關分子伴侶 Bip 及輔助伴侶 ERdjs. 生命的化學, 2020, 40(10): 1787-1791.
5.	張霞麗, 萬福生. X-盒結合蛋白 1 的病理生理學作用//華東六省一市生物化學與分子生物學會 2010 年學術交流會. 南昌: 中國生物化學與分子生物學會, 2010: 39.
6.	郭思維, 于雯, 王煦, 等. XBP1 在小鼠早期妊娠子宮的表達和調節. 生理學報, 2021, 73(2): 208-216.
7.	張文, 厲小梅, 徐東, 等. 原發性干燥綜合征診療規范. 中華內科雜志, 2020(4): 269-270.
8.	夏萍, 張梅兮, 穆森, 等. 舍格倫綜合征患者唾液 MMP-9 表達與組織病理分級相關性研究. 口腔醫學研究, 2017, 33(12): 1302-1305.
9.	Kroese FGM, Haacke EA, Bombardieri M. The role of salivary gland histopathology in primary Sj?gren’s syndrome: promises and pitfalls. Clin Exp Rheumatol, 2018, 36(3 Suppl 112): 222-233.
10.	劉麗, 李延萍, 吳斌, 等. 涎腺超聲在原發性干燥綜合征中的應用價值. 中國現代醫生, 2021, 59(1): 175-180.
11.	Campos J, Hillen MR, Barone F. Salivary gland pathology in Sj?gren’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, 李志軍. 干燥綜合征的診斷與治療. 中華全科醫學, 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 Sj?gren’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 Sj?gren’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 Sj?gren’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 Sj?gren’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 Sj?gren 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 (Sj?gren’s syndrome); the impact of metabolic status of glandular epithelial cells on auto-immunogenicity. J Autoimmun, 2019, 104: 102335.
4. 鄔珊珊, 廉姜芳. 內質網應激相關分子伴侶 Bip 及輔助伴侶 ERdjs. 生命的化學, 2020, 40(10): 1787-1791.
5. 張霞麗, 萬福生. X-盒結合蛋白 1 的病理生理學作用//華東六省一市生物化學與分子生物學會 2010 年學術交流會. 南昌: 中國生物化學與分子生物學會, 2010: 39.
6. 郭思維, 于雯, 王煦, 等. XBP1 在小鼠早期妊娠子宮的表達和調節. 生理學報, 2021, 73(2): 208-216.
7. 張文, 厲小梅, 徐東, 等. 原發性干燥綜合征診療規范. 中華內科雜志, 2020(4): 269-270.
8. 夏萍, 張梅兮, 穆森, 等. 舍格倫綜合征患者唾液 MMP-9 表達與組織病理分級相關性研究. 口腔醫學研究, 2017, 33(12): 1302-1305.
9. Kroese FGM, Haacke EA, Bombardieri M. The role of salivary gland histopathology in primary Sj?gren’s syndrome: promises and pitfalls. Clin Exp Rheumatol, 2018, 36(3 Suppl 112): 222-233.
10. 劉麗, 李延萍, 吳斌, 等. 涎腺超聲在原發性干燥綜合征中的應用價值. 中國現代醫生, 2021, 59(1): 175-180.
11. Campos J, Hillen MR, Barone F. Salivary gland pathology in Sj?gren’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, 李志軍. 干燥綜合征的診斷與治療. 中華全科醫學, 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 Sj?gren’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 Sj?gren’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 Sj?gren’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 Sj?gren’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 Sj?gren syndrome

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