Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2025
[Serum inter-alpha-trypsin inhibitor heavy chain H3 is identified as a potential biomarker for myopenia in patients with rheumatoid arthritis using proteomic profiling].
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Wu Tao, Lin Jianzi, Zhu Yafeng, Ma Jianda, Jia Peiwen, Yang Lijuan, Pan Jie, Zou Yaowei, Yang Ying, Lu Ye, Dai Lie
Аннотация
OBJECTIVE: To explore the serum biomarkers of myopenia in patients with rheumatoid arthritis (RA) via serum proteomic profiling.
METHODS: This cross-sectional study recruited active RA patients who either sustained non-myopenic or myopenia state over a 2-year follow-up period and unlabeled liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to analyze the serum proteomic profiles. Bioinformatics analyses were then applied to identify differentially expressed proteins between the two groups. Further validation cohort enrolled 102 RA patients (including 51 cases of non-myopenia group and 51 cases of myopenia group) and 51 healthy controls (HC) with age- and gender- matched propensity score at a 1 ∶ 1 ∶ 1 ratio. Enzyme-linked immunosorbent assay (ELISA) was used to verify the expression levels of the candidate protein. Multivariate logistic regression analysis was performed to identify baseline factors associated with myopenia in the RA patients.
RESULTS: Initial proteomic analysis of baseline serum samples from 9 non-myopenia RA patients and 10 myopenia RA patients identified 38 differentially expressed proteins. Among them, inter-alpha-trypsin inhibitor heavy chain H3 (ITIH3) showed a significant upregulation in the myopenia group (log2FC=2.09) and was consistently detected across all the samples. Subsequent ELISA validation confirmed that the serum ITIH3 level in 102 RA patients was significantly higher than that in 51 HC [(119.4±79.7) mg/L vs. (42.3±16.6) mg/L, P < 0.001], in which both myopenia group and non-myopenia group of the RA patients showed higher levels of serum ITIH3 than the HC group (both P < 0.001). Importantly, the serum ITIH3 level in the 51 patients with myopenia were significantly higher than that in the 51 patients without myopenia [(148.1±94.7) mg/L vs. (90.8±46.6) mg/L, P < 0.001]. After adjustment for confounding covariates including gender, age, disease duration, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), radiological joint destruction and previous treatment, the multivariate Logistic regression analysis showed that the baseline serum ITIH3 level was an independent risk factor for myopenia in the RA patients (OR=1.024, 95%CI: 1.013-1.038, P < 0.001).
CONCLUSION: This study identifies serum ITIH3 as a significant and independent risk factor for myopenia in patients with RA, which imply that ITIH3 might be a potential biomarker of myopenia. Further longitudinal large-sample multicenter validation is warranted to elucidate the precise role of ITIH3 in the pathophysiology of RA-associated myopenia and the clinical utility in risk stratification and management.
METHODS: This cross-sectional study recruited active RA patients who either sustained non-myopenic or myopenia state over a 2-year follow-up period and unlabeled liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to analyze the serum proteomic profiles. Bioinformatics analyses were then applied to identify differentially expressed proteins between the two groups. Further validation cohort enrolled 102 RA patients (including 51 cases of non-myopenia group and 51 cases of myopenia group) and 51 healthy controls (HC) with age- and gender- matched propensity score at a 1 ∶ 1 ∶ 1 ratio. Enzyme-linked immunosorbent assay (ELISA) was used to verify the expression levels of the candidate protein. Multivariate logistic regression analysis was performed to identify baseline factors associated with myopenia in the RA patients.
RESULTS: Initial proteomic analysis of baseline serum samples from 9 non-myopenia RA patients and 10 myopenia RA patients identified 38 differentially expressed proteins. Among them, inter-alpha-trypsin inhibitor heavy chain H3 (ITIH3) showed a significant upregulation in the myopenia group (log2FC=2.09) and was consistently detected across all the samples. Subsequent ELISA validation confirmed that the serum ITIH3 level in 102 RA patients was significantly higher than that in 51 HC [(119.4±79.7) mg/L vs. (42.3±16.6) mg/L, P < 0.001], in which both myopenia group and non-myopenia group of the RA patients showed higher levels of serum ITIH3 than the HC group (both P < 0.001). Importantly, the serum ITIH3 level in the 51 patients with myopenia were significantly higher than that in the 51 patients without myopenia [(148.1±94.7) mg/L vs. (90.8±46.6) mg/L, P < 0.001]. After adjustment for confounding covariates including gender, age, disease duration, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), radiological joint destruction and previous treatment, the multivariate Logistic regression analysis showed that the baseline serum ITIH3 level was an independent risk factor for myopenia in the RA patients (OR=1.024, 95%CI: 1.013-1.038, P < 0.001).
CONCLUSION: This study identifies serum ITIH3 as a significant and independent risk factor for myopenia in patients with RA, which imply that ITIH3 might be a potential biomarker of myopenia. Further longitudinal large-sample multicenter validation is warranted to elucidate the precise role of ITIH3 in the pathophysiology of RA-associated myopenia and the clinical utility in risk stratification and management.