Changes and clinical significance of serum CXCL13 and CHI3L1 levels in patients with autoimmune hepatitis

Abstract

Abstract: Objective To investigate the changes and clinical significance of serum levels of chemokine C-X-C motif ligand 13 (CXCL13) and chitinase-3-like protein 1 (CHI3L1) in patients with autoimmune hepatitis (AIH). Methods This study selected 115 patients diagnosed with AIH for the first time in our hospital from July 2022 to July 2024 as the AIH group. According to different stages of AIH, the patients were further divided into the active group (61 cases) and the remission group (54 cases). According to the severity of AIH, the patients were classified into the mild group (37 cases), moderate group (46 cases) and severe group (32 cases). In addition, 115 individuals who underwent physical health examinations were selected as the control group. Enzyme linked immunosorbent assay (ELISA) was applied to measure the expression levels of serum CXCL13 and CHI3L1. Logistic regression was applied to analyze factors affecting the severity of AIH. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of CXCL13 and CHI3L1 in the severity of AIH patients. Results The serum levels of CXCL13 and CHI3L1 in patients with AIH were (287.82±31.76) pg/mL and (739.27±64.51) pg/mL, respectively, which were higher than those in control group (212.15±26.21) pg/mL and (575.54±52.48) pg/mL (P<0.05). With the aggravation of AIH severity, the serum levels of CXCL13 and CHI3L1 increased significantly in mild group (261.62±29.73) pg/mL, (682.14±61.38) pg/mL, moderate group (284.45±31.48) pg/mL, (744.15±64.41) pg/mL and severe group (322.97±34.52) pg/mL,(798.31±68.26) pg/mL (P<0.05). Alanine aminotransferase[(122.14±5.31) U/L vs. (72.25±2.29)U/L], aspartate aminotransferase[(166.37±5.86) U/L vs. (79.87±3.78) U/L], CXCL13[(308.51±32.92) pg/mL vs. (264.44±30.45) pg/mL] and CHI3L1[(771.49±68.14) pg/mL vs. (702.87±60.41) pg/mL] in remission group and active group were significantly different (P<0.05). Logistic analysis showed that CXCL13 and CHI3L1 were risk factors affecting the severity of AIH patients (OR＞1, P<0.05). The AUC of the combined diagnosis of serum CXCL13 and CHI3L1 for the severity of AIH patients was the highest, superior to the individual diagnosis of CXCL13 and CHI3L1 (Z_{combination-CXCL13}=2.093, P=0.036, Z_{combination-CHI3L1}=3.295, P=0.001), with a sensitivity of 75.00% and a specificity of 95.18%. Conclusion The levels of serum CXCL13 and CHI3L1 are obviously elevated in AIH patients, and their combination can better evaluate the severity of AIH patients.

Key words: Autoimmune hepatitis, CXCL13, CHI3L1, Diagnosis

BAO Zhuo, BAO Yu-rong, Aoduntuoya. Changes and clinical significance of serum CXCL13 and CHI3L1 levels in patients with autoimmune hepatitis[J]. Chinese Hepatolgy, 2026, 31(1): 54-58.

References

[1] Muratori L, Lohse A W, Lenzi M. Diagnosis and management of autoimmune hepatitis[J]. BMJ. 2023 Feb 6, 380:e070201.
[2] Olivas I, Rodríguez-Tajes S, Londoño M C. Autoimmune hepatitis: challenges and novelties[J]. Med Clin (Barc), 2022 , 159(6): 289-298.
[3] Sirbe C, Simu G, Szabo I, et al. Pathogenesis of autoimmune hepatitis-cellular and molecular mechanisms[J]. Int J Mol Sci, 2021, 22(24): 13578.
[4] Terziroli Beretta-Piccoli B, Mieli-Vergani G, Vergani D. Autoimmune hepatitis: serum autoantibodies in clinical practice[J]. Clin Rev Allergy Immunol, 2022 , 63(2): 124-137.
[5] Wang B, Wang M, Ao D, et al. CXCL13-CXCR5 axis: regulation in inflammatory diseases and cancer[J]. Biochim Biophys Acta Rev Cancer, 2022, 1877(5): 188799.
[6] Harrer C, Otto F, Radlberger R F, et al. The CXCL13/CXCR5 immune axis in health and disease-implications for intrathecal B cell activities in neuroinflammation[J]. Cells, 2022 , 11(17): 2649.
[7] Pan Z, Zhu T, Liu Y, et al. Role of the CXCL13/CXCR5 axis in autoimmune diseases[J]. Front Immunol,2022 , 13: 850998.
[8] Connolly K, Lehoux M, O′Rourke R, et al. Potential role of chitinase-3-like protein 1 (CHI3L1/YKL-40) in neurodegeneration and Alzheimer′s disease[J]. Alzheimers Dement, 2023 19(1): 9-24.
[9] Wang S, Hu M, Qian Y, et al. CHI3L1 in the pathophysiology and diagnosis of liver diseases[J]. Biomed Pharmacother, 2020, 131, 110680.
[10] 中华医学会肝病学分会. 自身免疫性肝炎诊断和治疗指南(2021)[J]. 中华内科杂志, 2021, 60(12): 1038-1049.
[11] Flikshteyn B, Amer K, Tafesh Z, et al. Diagnosis of autoimmune hepatitis[J]. Clin Liver Dis, 2024, 28(1): 37-50.
[12] Harrington C, Krishnan S, Mack C L, et al. Noninvasive biomarkers for the diagnosis and management of autoimmune hepatitis[J]. Hepatology, 2022 , 76(6): 1862-1879.
[13] Ren J, Lan T, Liu T, et al. CXCL13 as a novel immune checkpoint for regulatory B cells and its role in tumor metastasis[J]. J Immunol, 2022 , 208(10): 2425-2435.
[14] Liu H, Bai Y, Li F, et al. Combined serum CXCL8, CXCL9 and CXCL13 tests for the prediction of microvascular invasion in hepatocellular carcinoma[J]. Biomark Med, 2023 , 17(5): 265-272.
[15] 毕恒. 血清趋化因子-13、白细胞介素-6、白细胞介素-18在慢性乙型病毒性肝炎患者中的表达意义[J]. 河南医学研究, 2022, 31(24): 4459-4462.
[16] Luo M, Zhang L, Yang C, et al. CXCL13 variant predicts pegylated-interferon α treatment response in HBeAg-positive chronic hepatitis B patients[J]. J Med Virol, 2023, 95(7):e28963.
[17] Zhu B, Gao F, Li Y, et al. Serum cytokine and chemokine profiles and disease prognosis in hepatitis B virus-related acute-on-chronic liver failure[J]. Front Immunol, 2023 , 14:1133656.
[18] Hu X, Liu W, Liu J, et al. Research advances in serum chitinase-3-like protein 1 in liver fibrosis[J]. Front Med (Lausanne), 2024 , 11: 1372434.
[19] Zhao T, Su Z, Li Y, et al. Chitinase-3 like-protein-1 function and its role in diseases[J]. Signal Transduct Target Ther, 2020, 5(1): 201.
[20] Wang S, Chen S, Jin M, et al. Diagnostic and prognostic value of serum Chitinase 3-like protein 1 in hepatocellular carcinoma[J]. J Clin Lab Anal, 2022 , 36(2):e24234.
[21] 卢瑾,闻名,唐情容,等. 血清GP73、CHI3L1表达与慢性乙型肝炎患者肝纤维化及病理变化程度的关系[J]. 实用医学杂志, 2024, 40(11): 1586-1591.
[22] Kim M, Chang J Y, Lee D W, et al. Chitinase 3 like 1 deficiency ameliorates lipopolysaccharide-induced acute liver injury by inhibition of M2 macrophage polarization[J]. Mol Immunol, 2023, 156(1):98-110.
[23] Shan Z, Li L, Atkins C L, et al. Chitinase 3-like-1 contributes to acetaminophen-induced liver injury by promoting hepatic platelet recruitment[J]. Elife, 2021, 10:e68571.