Anti-Tyro3 IgG Associates with Disease Activity and Reduces Efferocytosis of Macrophages in New-Onset Systemic Lupus Erythematosus
Background. Systemic lupus erythematosus (SLE) is a disease characterized by the production of a large number of autoantibodies. Defected phagocytosis of macrophage plays an important role in innate immunity in the pathogenesis of SLE. Tyro3 is a receptor responsible for the recognition of apoptotic...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2020-01-01
|
| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2020/2180708 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850218474227367936 |
|---|---|
| author | Zhuochao Zhou Aining Xu Jialin Teng Fan Wang Yun Tan Honglei Liu Xiaobing Cheng Yutong Su Hui Shi Qiongyi Hu Huihui Chi Jian Li Jiaqi Hou Yue Sun Chengde Yang Junna Ye |
| author_facet | Zhuochao Zhou Aining Xu Jialin Teng Fan Wang Yun Tan Honglei Liu Xiaobing Cheng Yutong Su Hui Shi Qiongyi Hu Huihui Chi Jian Li Jiaqi Hou Yue Sun Chengde Yang Junna Ye |
| author_sort | Zhuochao Zhou |
| collection | DOAJ |
| description | Background. Systemic lupus erythematosus (SLE) is a disease characterized by the production of a large number of autoantibodies. Defected phagocytosis of macrophage plays an important role in innate immunity in the pathogenesis of SLE. Tyro3 is a receptor responsible for the recognition of apoptotic cells during efferocytosis by macrophages. To investigate the role of Tyro3 receptor in macrophages’ efferocytosis of apoptotic cells in SLE, we aimed to reveal the clinical relevance and impact of Tyro3 autoantibody on SLE. Methods. The serum levels of IgG-type autoantibody against Tyro3 receptor were detected in new-onset, treatment-naïve SLE patients (n=70), rheumatoid arthritis (RA) (n=24), primary Sjögren’s Syndrome (pSS) (n=21), and healthy controls (HCs) (n=70) using enzyme-linked immunosorbent assay (ELISA). The effects of purified Tyro3 autoantibody from SLE patients on the efferocytosis of human monocyte-derived macrophages were measured by flow cytometry and immunofluorescence. Results. The serum levels of IgG-type autoantibody against Tyro3 receptor were significantly elevated in patients with SLE compared to RA, pSS, and HCs (all p<0.0001). The levels of anti-Tyro3 IgG were positively associated with the SLE disease activity index (SLEDAI) score (r=0.254, p=0.034), erythrocyte sedimentation rate (ESR) (r=0.430, p<0.001), C-reactive protein (CRP) (r=0.246, p=0.049), and immunoglobulin G (IgG) (r=0.408, p=0.001) and negatively associated with haemoglobin (Hb) (r=−0.294, p=0.014). ROC curves illustrated that the anti-Tyro3 antibody could differentiate patients with SLE from HCs. Furthermore, flow cytometry and immunofluorescence demonstrated that purified anti-Tyro3 IgG inhibited the efferocytosis of macrophages (p=0.004 and 0.044, respectively) compared with unconjugated human IgG. Conclusions. These observations indicated that autoantibody against Tyro3 was associated with disease activity and could impair efferocytosis of macrophages. It might be a potential novel disease biomarker and might be involved in the pathogenesis of SLE. |
| format | Article |
| id | doaj-art-378b6e13fbb34c9bbc6d4973fa93c371 |
| institution | OA Journals |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-378b6e13fbb34c9bbc6d4973fa93c3712025-08-20T02:07:44ZengWileyJournal of Immunology Research2314-88612314-71562020-01-01202010.1155/2020/21807082180708Anti-Tyro3 IgG Associates with Disease Activity and Reduces Efferocytosis of Macrophages in New-Onset Systemic Lupus ErythematosusZhuochao Zhou0Aining Xu1Jialin Teng2Fan Wang3Yun Tan4Honglei Liu5Xiaobing Cheng6Yutong Su7Hui Shi8Qiongyi Hu9Huihui Chi10Jian Li11Jiaqi Hou12Yue Sun13Chengde Yang14Junna Ye15Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaState Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaState Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaClinical Research Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Rheumatology and Immunology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaBackground. Systemic lupus erythematosus (SLE) is a disease characterized by the production of a large number of autoantibodies. Defected phagocytosis of macrophage plays an important role in innate immunity in the pathogenesis of SLE. Tyro3 is a receptor responsible for the recognition of apoptotic cells during efferocytosis by macrophages. To investigate the role of Tyro3 receptor in macrophages’ efferocytosis of apoptotic cells in SLE, we aimed to reveal the clinical relevance and impact of Tyro3 autoantibody on SLE. Methods. The serum levels of IgG-type autoantibody against Tyro3 receptor were detected in new-onset, treatment-naïve SLE patients (n=70), rheumatoid arthritis (RA) (n=24), primary Sjögren’s Syndrome (pSS) (n=21), and healthy controls (HCs) (n=70) using enzyme-linked immunosorbent assay (ELISA). The effects of purified Tyro3 autoantibody from SLE patients on the efferocytosis of human monocyte-derived macrophages were measured by flow cytometry and immunofluorescence. Results. The serum levels of IgG-type autoantibody against Tyro3 receptor were significantly elevated in patients with SLE compared to RA, pSS, and HCs (all p<0.0001). The levels of anti-Tyro3 IgG were positively associated with the SLE disease activity index (SLEDAI) score (r=0.254, p=0.034), erythrocyte sedimentation rate (ESR) (r=0.430, p<0.001), C-reactive protein (CRP) (r=0.246, p=0.049), and immunoglobulin G (IgG) (r=0.408, p=0.001) and negatively associated with haemoglobin (Hb) (r=−0.294, p=0.014). ROC curves illustrated that the anti-Tyro3 antibody could differentiate patients with SLE from HCs. Furthermore, flow cytometry and immunofluorescence demonstrated that purified anti-Tyro3 IgG inhibited the efferocytosis of macrophages (p=0.004 and 0.044, respectively) compared with unconjugated human IgG. Conclusions. These observations indicated that autoantibody against Tyro3 was associated with disease activity and could impair efferocytosis of macrophages. It might be a potential novel disease biomarker and might be involved in the pathogenesis of SLE.http://dx.doi.org/10.1155/2020/2180708 |
| spellingShingle | Zhuochao Zhou Aining Xu Jialin Teng Fan Wang Yun Tan Honglei Liu Xiaobing Cheng Yutong Su Hui Shi Qiongyi Hu Huihui Chi Jian Li Jiaqi Hou Yue Sun Chengde Yang Junna Ye Anti-Tyro3 IgG Associates with Disease Activity and Reduces Efferocytosis of Macrophages in New-Onset Systemic Lupus Erythematosus Journal of Immunology Research |
| title | Anti-Tyro3 IgG Associates with Disease Activity and Reduces Efferocytosis of Macrophages in New-Onset Systemic Lupus Erythematosus |
| title_full | Anti-Tyro3 IgG Associates with Disease Activity and Reduces Efferocytosis of Macrophages in New-Onset Systemic Lupus Erythematosus |
| title_fullStr | Anti-Tyro3 IgG Associates with Disease Activity and Reduces Efferocytosis of Macrophages in New-Onset Systemic Lupus Erythematosus |
| title_full_unstemmed | Anti-Tyro3 IgG Associates with Disease Activity and Reduces Efferocytosis of Macrophages in New-Onset Systemic Lupus Erythematosus |
| title_short | Anti-Tyro3 IgG Associates with Disease Activity and Reduces Efferocytosis of Macrophages in New-Onset Systemic Lupus Erythematosus |
| title_sort | anti tyro3 igg associates with disease activity and reduces efferocytosis of macrophages in new onset systemic lupus erythematosus |
| url | http://dx.doi.org/10.1155/2020/2180708 |
| work_keys_str_mv | AT zhuochaozhou antityro3iggassociateswithdiseaseactivityandreducesefferocytosisofmacrophagesinnewonsetsystemiclupuserythematosus AT ainingxu antityro3iggassociateswithdiseaseactivityandreducesefferocytosisofmacrophagesinnewonsetsystemiclupuserythematosus AT jialinteng antityro3iggassociateswithdiseaseactivityandreducesefferocytosisofmacrophagesinnewonsetsystemiclupuserythematosus AT fanwang antityro3iggassociateswithdiseaseactivityandreducesefferocytosisofmacrophagesinnewonsetsystemiclupuserythematosus AT yuntan antityro3iggassociateswithdiseaseactivityandreducesefferocytosisofmacrophagesinnewonsetsystemiclupuserythematosus AT hongleiliu antityro3iggassociateswithdiseaseactivityandreducesefferocytosisofmacrophagesinnewonsetsystemiclupuserythematosus AT xiaobingcheng antityro3iggassociateswithdiseaseactivityandreducesefferocytosisofmacrophagesinnewonsetsystemiclupuserythematosus AT yutongsu antityro3iggassociateswithdiseaseactivityandreducesefferocytosisofmacrophagesinnewonsetsystemiclupuserythematosus AT huishi antityro3iggassociateswithdiseaseactivityandreducesefferocytosisofmacrophagesinnewonsetsystemiclupuserythematosus AT qiongyihu antityro3iggassociateswithdiseaseactivityandreducesefferocytosisofmacrophagesinnewonsetsystemiclupuserythematosus AT huihuichi antityro3iggassociateswithdiseaseactivityandreducesefferocytosisofmacrophagesinnewonsetsystemiclupuserythematosus AT jianli antityro3iggassociateswithdiseaseactivityandreducesefferocytosisofmacrophagesinnewonsetsystemiclupuserythematosus AT jiaqihou antityro3iggassociateswithdiseaseactivityandreducesefferocytosisofmacrophagesinnewonsetsystemiclupuserythematosus AT yuesun antityro3iggassociateswithdiseaseactivityandreducesefferocytosisofmacrophagesinnewonsetsystemiclupuserythematosus AT chengdeyang antityro3iggassociateswithdiseaseactivityandreducesefferocytosisofmacrophagesinnewonsetsystemiclupuserythematosus AT junnaye antityro3iggassociateswithdiseaseactivityandreducesefferocytosisofmacrophagesinnewonsetsystemiclupuserythematosus |