Disease-Specific Autoantibodies Induce Trained Immunity in RA Synovial Tissues and Its Gene Signature Correlates with the Response to Clinical Therapy
Much evidence suggests that trained immunity is inappropriately activated in the synovial tissue in rheumatoid arthritis (RA), but the underlying mechanism remains unclear. Here, we describe how RA-specific autoantibody deposits can train human monocytes to exert the hyperactive inflammatory respons...
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2020/2109325 |
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| author | Xiaoli Dai Xiaoqiu Dai Zheng Gong Chen Yang Keqin Zeng Fang-Yuan Gong Qiao Zhong Xiao-Ming Gao |
| author_facet | Xiaoli Dai Xiaoqiu Dai Zheng Gong Chen Yang Keqin Zeng Fang-Yuan Gong Qiao Zhong Xiao-Ming Gao |
| author_sort | Xiaoli Dai |
| collection | DOAJ |
| description | Much evidence suggests that trained immunity is inappropriately activated in the synovial tissue in rheumatoid arthritis (RA), but the underlying mechanism remains unclear. Here, we describe how RA-specific autoantibody deposits can train human monocytes to exert the hyperactive inflammatory response, particularly via the exacerbated release of tumor necrosis factor α (TNFα). Comparative transcriptomic analysis by plate-bound human IgG (cIgG) or β-glucan indicated that metabolic shift towards glycolysis is a crucial mechanism for trained immunity. Moreover, the cIgG-trained gene signatures were enriched in synovial tissues from patients with ACPA- (anticitrullinated protein antibody-) positive arthralgia and undifferentiated arthritis, and early RA and established RA bore a great resemblance to the myeloid pathotype, suggesting a historical priming event in vivo. Additionally, the expression of the cIgG-trained signatures is higher in the female, older, and ACPA-positive populations, with a predictive role in the clinical response to infliximab. We conclude that RA-specific autoantibodies can train monocytes in the inflamed lesion as early as the asymptomatic stage, which may not merely improve understanding of disease progression but may also suggest therapeutic and/or preventive strategies for autoimmune diseases. |
| format | Article |
| id | doaj-art-9af6aaa5e5d1458fa5f9e69c14ab9ceb |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-9af6aaa5e5d1458fa5f9e69c14ab9ceb2025-02-03T06:00:48ZengWileyMediators of Inflammation0962-93511466-18612020-01-01202010.1155/2020/21093252109325Disease-Specific Autoantibodies Induce Trained Immunity in RA Synovial Tissues and Its Gene Signature Correlates with the Response to Clinical TherapyXiaoli Dai0Xiaoqiu Dai1Zheng Gong2Chen Yang3Keqin Zeng4Fang-Yuan Gong5Qiao Zhong6Xiao-Ming Gao7Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou 215009, ChinaInstitute of Biology and Medical Sciences, Soochow University, Suzhou 215123, ChinaInstitute of Biology and Medical Sciences, Soochow University, Suzhou 215123, ChinaDepartment of Laboratory Medicine, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou 215002, ChinaDepartment of Rheumatology, The First Affiliated Hospital of Soochow University, Suzhou 215002, ChinaInstitute of Biology and Medical Sciences, Soochow University, Suzhou 215123, ChinaDepartment of Laboratory Medicine, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou 215002, ChinaInstitute of Biology and Medical Sciences, Soochow University, Suzhou 215123, ChinaMuch evidence suggests that trained immunity is inappropriately activated in the synovial tissue in rheumatoid arthritis (RA), but the underlying mechanism remains unclear. Here, we describe how RA-specific autoantibody deposits can train human monocytes to exert the hyperactive inflammatory response, particularly via the exacerbated release of tumor necrosis factor α (TNFα). Comparative transcriptomic analysis by plate-bound human IgG (cIgG) or β-glucan indicated that metabolic shift towards glycolysis is a crucial mechanism for trained immunity. Moreover, the cIgG-trained gene signatures were enriched in synovial tissues from patients with ACPA- (anticitrullinated protein antibody-) positive arthralgia and undifferentiated arthritis, and early RA and established RA bore a great resemblance to the myeloid pathotype, suggesting a historical priming event in vivo. Additionally, the expression of the cIgG-trained signatures is higher in the female, older, and ACPA-positive populations, with a predictive role in the clinical response to infliximab. We conclude that RA-specific autoantibodies can train monocytes in the inflamed lesion as early as the asymptomatic stage, which may not merely improve understanding of disease progression but may also suggest therapeutic and/or preventive strategies for autoimmune diseases.http://dx.doi.org/10.1155/2020/2109325 |
| spellingShingle | Xiaoli Dai Xiaoqiu Dai Zheng Gong Chen Yang Keqin Zeng Fang-Yuan Gong Qiao Zhong Xiao-Ming Gao Disease-Specific Autoantibodies Induce Trained Immunity in RA Synovial Tissues and Its Gene Signature Correlates with the Response to Clinical Therapy Mediators of Inflammation |
| title | Disease-Specific Autoantibodies Induce Trained Immunity in RA Synovial Tissues and Its Gene Signature Correlates with the Response to Clinical Therapy |
| title_full | Disease-Specific Autoantibodies Induce Trained Immunity in RA Synovial Tissues and Its Gene Signature Correlates with the Response to Clinical Therapy |
| title_fullStr | Disease-Specific Autoantibodies Induce Trained Immunity in RA Synovial Tissues and Its Gene Signature Correlates with the Response to Clinical Therapy |
| title_full_unstemmed | Disease-Specific Autoantibodies Induce Trained Immunity in RA Synovial Tissues and Its Gene Signature Correlates with the Response to Clinical Therapy |
| title_short | Disease-Specific Autoantibodies Induce Trained Immunity in RA Synovial Tissues and Its Gene Signature Correlates with the Response to Clinical Therapy |
| title_sort | disease specific autoantibodies induce trained immunity in ra synovial tissues and its gene signature correlates with the response to clinical therapy |
| url | http://dx.doi.org/10.1155/2020/2109325 |
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