High serum level of haptoglobin is associated with the response of 12 weeks methotrexate therapy in recent‐onset rheumatoid arthritis patients

Tan, Wenfeng; Wang, Fang; Guo, Dan; Ke, Yao; Shen, Ya; Lv, Chengyin; Zhang, Miaojia

doi:10.1111/1756-185x.12380

Cited by 12 publications

(6 citation statements)

References 29 publications

(40 reference statements)

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“…1). The results were similar to studies that demonstrated that HP is an important activator of immune cells (16)(17)(18). Based on these results, we conjectured that HP plays important roles in B-cell activation.…”

Section: Discussionsupporting

confidence: 89%

Identification of an activation‑related protein in B cells in the ABO incompatible condition

et al. 2019

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In ABO-incompatible (ABOi) kidney transplantation (KT), antibodies can mediate immunological accommodation or immune rejection, but the mechanism by which B cells are induced to produce antibodies with different functions is still unclear. Previous research established an ABOi kidney cell model and identified that haptoglobin (HP) is associated with the activation of lymphocytes. In the present study, the results of a flow cytometric assay demonstrated that HP was expressed by B cells. Moreover, dot-ELISA and ELISA analyses showed that the concentrations of total IgG, blood group B antibody, IgG1, IgG2 and IgG4 were all significantly increased in the cell model. In addition, dot-ELISA and haptoglobin level analyses showed that HP protein expression was significantly increased, while RT-qPCR assay indicated that HP was significantly reduced at the mRNA level. Furthermore, bioinformatics analysis showed that HP could interact with Smad3, and the HP-Smad3 complex was detected in a peripheral blood mononuclear cell (PBMC) protein extract by a dot-ELISA method. This research revealed that HP was involved in the process of B-cell activation by interacting with Smad3, and the results will be helpful to reveal the mechanism of B-cell activation in ABOi-KT.

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Section: Discussionsupporting

confidence: 89%

Identification of an activation‑related protein in B cells in the ABO incompatible condition

et al. 2019

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“…As a result, the mRNA level of haptoglobin in CIKs treated with gentamicin was significantly downregulated by 1.73-fold compared with the control group. This is similar to the finding that haptoglobin expression signal was decreased 5.1-fold in peripheral blood mononuclear cells from healthy participants compared with methotrexate-resistant patients with rheumatoid arthritis (38). Herein, these results suggest that haptoglobin was involved in the activity-enhancement of CIKs.…”

Section: Discussionsupporting

confidence: 88%

Identification of a protein associated with the activity of cytokine‑induced killer cells

et al. 2017

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Abstract. Cytokine-induced killer cells (CIKs) adoptive immunotherapy for efficient antitumor ability is used clinically, but details regarding the proteins associated with CIK activity remain unclear. In the current study, the cytotoxicity of CIKs on hepatoma was identified to be significantly downregulated by 1.61-fold following gentamincin treatment. Further research revealed that a differentially expressed protein (P43) was significantly downregulated by 1.22-fold using one-dimensional gel electrophoresis analysis. Of these, the P43 was identified as human haptoglobin using liquid chromatography-mass spectrometry. Western blotting demonstrated that the haptoglobin specifically reacted with rabbit anti-human-haptoglobin. Furthermore, western blotting results verified that the haptoglobin was significantly downregulated by 1.17-fold compared with the control group. In addition, the expression of haptoglobin mRNA was significantly downregulated by 1.73-fold following gentamincin treatment. Taken together, the results of the present study demonstrated that the expression of haptoglobin protein was associated with the activity of CIKs, and the results will be beneficial to the further investigation of CIK activity-enhancement mechanism.

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“…A similar association with serum TNF-α was found by another research group 21 . In a Chinese study of patients with eRA, it was shown that high serum levels of haptoglobin were associated with response to MTX therapy 22 . A study of treatment-naive eRA patients in India demonstrated that serum baseline levels of myeloid-related protein 8/14 were significantly higher in responders versus nonresponders to 4 months of MTX monotherapy, according to European League Against Rheumatism (EULAR) criteria 23 .…”

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confidence: 99%

Serum Biomarkers for Prediction of Response to Methotrexate Monotherapy in Early Rheumatoid Arthritis: Results from the SWEFOT Trial

Hambardzumyan

Bolce²,

Wallman³

et al. 2019

J Rheumatol

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Objective.To investigate baseline levels of 12 serum biomarkers that constitute a multibiomarker disease activity test, as predictors of response to methotrexate (MTX) in patients with early rheumatoid arthritis (eRA).Methods.In 298 patients from the Swedish Pharmacotherapy (SWEFOT) clinical trial, baseline serum levels of 12 proteins were analyzed for association with disease activity based on the 28-joint count Disease Activity Score (DAS28) after 3 months of MTX monotherapy using uni-/multivariate logistic regression. Primary outcome was low disease activity (LDA; DAS28 ≤ 3.2).Results.Of 298 patients, 104 achieved LDA after 3 months on MTX. Four of the 12 biomarkers [C-reactive protein (CRP), leptin, tumor necrosis factor receptor I (TNF-RI), and vascular cell adhesion molecule 1 (VCAM-1)] significantly predicted LDA based on stepwise logistic regression analysis. Dichotomization of patients using receiver-operating characteristic curve analysis-based cutoffs for these biomarkers showed significantly higher proportions with LDA among patients with lower versus higher levels of CRP or leptin (40% vs 23%, p = 0.004, and 40% vs 25%, p = 0.011, respectively), as well as among those with higher versus lower levels of TNF-RI or VCAM-1 (43% vs 27%, p = 0.004, and 41% vs 25%, p = 0.004, respectively). Combined score based on these biomarkers, adjusted for known predictors of LDA (smoking, sex, and age), associated with decreased chance of LDA (adjusted OR 0.45, 95% CI 0.32–0.62).Conclusion.Low baseline levels of CRP and leptin, and high baseline levels of TNF-RI and VCAM-1 were associated with LDA after 3 months of MTX therapy in patients with eRA. Combination of these 4 biomarkers increased accuracy of prediction. [Trial registration number: NCT00764725]

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High serum level of haptoglobin is associated with the response of 12 weeks methotrexate therapy in recent‐onset rheumatoid arthritis patients

Abstract: Background: We previously found, using microarray, haptoglobin (HP) expression signal was 5.1-fold increased in peripheral blood mononuclear cells (PBMCs) from methotrexate (MTX)-resistant rheumatoid arthritis (RA) patients.

Cited by 12 publications

References 29 publications

Identification of an activation‑related protein in B cells in the ABO incompatible condition

Identification of an activation‑related protein in B cells in the ABO incompatible condition

Identification of a protein associated with the activity of cytokine‑induced killer cells

Serum Biomarkers for Prediction of Response to Methotrexate Monotherapy in Early Rheumatoid Arthritis: Results from the SWEFOT Trial

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