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CD74 是脊柱关节炎中的 T 细胞抗原。

CD74 is a T cell antigen in spondyloarthritis.

机构信息

Division of Immunology and Rheumatology, Hannover Medical University, Hannover, Germany.

Aesku.Diagnostics, Wendelsheim, Germany.

出版信息

Clin Exp Rheumatol. 2020 Mar-Apr;38(2):195-202. doi: 10.55563/clinexprheumatol/lezc69. Epub 2019 May 22.

Abstract

OBJECTIVES

Spondyloarthritis (SpA) is a chronic inflammatory disease of unknown aetiology. Previously, we identified autoantibodies against CD74 in sera of SpA patients. The aim of this study was to evaluate CD74 as a T cell antigen in SpA.

METHODS

Recombinant CD74 protein and a panel of selected peptides representing its amino acid residues were examined for their capability to stimulate peripheral blood mononuclear cells from patients with SpA. In particular, cytokine production by CD4+ T cells was evaluated with flow cytometric detection of intracellular TNF-α, IFNγ, TGFβ and IL-17A. Patients' sera were tested for antibodies against CD74 using ELISA. Samples from patients with rheumatoid arthritis and healthy blood donors were similarly tested as controls.

RESULTS

Significantly more CD4+ T cells from SpA patients produced TNF-α, IFNγ and IL-17A in response to recombinant CD74 than patients with rheumatoid arthritis or healthy blood donors. Among evaluated epitopes, the most promiscuous one lies within the peptide of the amino acid residues 142-185, which appeared more immunogenic. Further, the proportion of cytokine producing CD4+ T cells was significantly higher among SpA patients with autoantibodies against CD74.

CONCLUSIONS

CD74 is a T cell antigen in SpA, eliciting Th1 and Th17 responses, which may be relevant in disease pathogenesis. Recognition of the highly immunogenic amino acid residues of CD74 may contribute to our understanding of autoimmune responses of T helper cells in SpA.

摘要

目的

脊柱关节炎(SpA)是一种病因不明的慢性炎症性疾病。此前,我们在 SpA 患者的血清中发现了针对 CD74 的自身抗体。本研究旨在评估 CD74 作为 SpA 中的 T 细胞抗原。

方法

检测重组 CD74 蛋白和一组代表其氨基酸残基的选定肽段,以评估它们刺激 SpA 患者外周血单个核细胞的能力。特别地,通过流式细胞术检测细胞内 TNF-α、IFNγ、TGFβ 和 IL-17A 来评估 CD4+T 细胞的细胞因子产生。使用 ELISA 检测患者血清中针对 CD74 的抗体。将类风湿关节炎患者和健康献血者的样本作为对照进行类似检测。

结果

与类风湿关节炎患者或健康献血者相比,来自 SpA 患者的 CD4+T 细胞对重组 CD74 的 TNF-α、IFNγ 和 IL-17A 产生明显更多。在所评估的表位中,最具混杂性的表位位于氨基酸残基 142-185 的肽段内,该肽段似乎更具免疫原性。此外,在具有针对 CD74 的自身抗体的 SpA 患者中,产生细胞因子的 CD4+T 细胞的比例明显更高。

结论

CD74 是 SpA 中的 T 细胞抗原,引发 Th1 和 Th17 反应,这可能与疾病发病机制有关。对 CD74 的高度免疫原性氨基酸残基的识别可能有助于我们理解 SpA 中 T 辅助细胞的自身免疫反应。

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