High-titer anti-interferon-γ neutralizing autoantibodies linked to opportunistic infections in patients with adult-onset still's disease
ObjectiveNeutralizing anti-interferon (IFN)-γ autoantibodies are linked to opportunistic infections (OIs). To explore the association between anti-IFN-γ autoantibodies and OIs in patients with adult-onset Still's disease (AOSD), we aimed to examine the ability of these autoantibodies to blockad...
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2022.1097514/full |
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| author | Po-Ku Chen Po-Ku Chen Po-Ku Chen Tsai-Ling Liao Tsai-Ling Liao Shih-Hsin Chang Shih-Hsin Chang Shih-Hsin Chang Kai-Jieh Yeo Kai-Jieh Yeo Chia-Hui Chou Chia-Hui Chou Der-Yuan Chen Der-Yuan Chen Der-Yuan Chen Der-Yuan Chen |
| author_facet | Po-Ku Chen Po-Ku Chen Po-Ku Chen Tsai-Ling Liao Tsai-Ling Liao Shih-Hsin Chang Shih-Hsin Chang Shih-Hsin Chang Kai-Jieh Yeo Kai-Jieh Yeo Chia-Hui Chou Chia-Hui Chou Der-Yuan Chen Der-Yuan Chen Der-Yuan Chen Der-Yuan Chen |
| author_sort | Po-Ku Chen |
| collection | DOAJ |
| description | ObjectiveNeutralizing anti-interferon (IFN)-γ autoantibodies are linked to opportunistic infections (OIs). To explore the association between anti-IFN-γ autoantibodies and OIs in patients with adult-onset Still's disease (AOSD), we aimed to examine the ability of these autoantibodies to blockade signal transducer and activator of transcription (STAT1)-phosphorylation and chemokines production.MethodsSerum titers of anti-IFN-γ autoantibodies were quantified using ELISA in 29 AOSD and 22 healthy controls (HC). The detectable autoantibodies were verified with immunoblotting assay, and their neutralizing capacity against IFN-γ-signaling was evaluated with flow-cytometry analysis and immunoblotting. IFN-γ-mediated production of supernatant chemokines, including monocyte chemoattractant protein-1 (MCP-1) and IFN-γ inducible protein-10 (IP-10), were measured by ELISA.ResultsAmong 29 AOSD patients, high titers of anti-IFN-γ neutralizing autoantibodies were detectable in two patients with OIs. Immunoblotting assay revealed more effective inhibition of STAT1-phosphorylation in THP-1 cells treated with sera from autoantibody-positive AOSD patients (56.7 ± 34.79%) compared with those from HC (104.3 ±29.51%), which was also demonstrated in flow-cytometry analysis (47.13 ± 40.99 vs. 97.92 ± 9.48%, p < 0.05). Depleted serum IgG from anti-IFN-γ autoAbs-positive AOSD patients with OIs restored phosphorylated STAT-1 upon IFN-γ treatment. Sera from autoantibody-positive AOSD patients more effectively inhibited IFN-γ-mediated production of MCP-1 (45.65 pg/ml) and IP-10 (22.44 pg/ml) than sera from HC (263.1 pg/ml and 104.0 pg/ml, both p < 0.05). Serum samples showing the strongest inhibition of IFN-γ-signaling were from two patients with high-titer autoantibodies and OIs.ConclusionAOSD patients have a high positive rate and titers of anti-IFN-γ autoantibodies. The remarkable blockade effect of high-titer autoantibodies on IFN-γ-mediated STAT1-phosphorylation and chemokines could make these patients susceptible to OIs. |
| first_indexed | 2024-04-11T00:04:00Z |
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| language | English |
| last_indexed | 2024-04-11T00:04:00Z |
| publishDate | 2023-01-01 |
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| spelling | doaj.art-0c23bb4aeb2d41ebb57ec566ca2d4afa2023-01-09T12:16:40ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2023-01-01910.3389/fmed.2022.10975141097514High-titer anti-interferon-γ neutralizing autoantibodies linked to opportunistic infections in patients with adult-onset still's diseasePo-Ku Chen0Po-Ku Chen1Po-Ku Chen2Tsai-Ling Liao3Tsai-Ling Liao4Shih-Hsin Chang5Shih-Hsin Chang6Shih-Hsin Chang7Kai-Jieh Yeo8Kai-Jieh Yeo9Chia-Hui Chou10Chia-Hui Chou11Der-Yuan Chen12Der-Yuan Chen13Der-Yuan Chen14Der-Yuan Chen15Rheumatology and Immunology Center, China Medical University Hospital, Taichung, TaiwanCollege of Medicine, China Medical University, Taichung, TaiwanTranslational Medicine Laboratory, Rheumatology and Immunology Center, Taichung, TaiwanPh.D. Program in Translational Medicine and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, TaiwanDepartment of Medical Research, Taichung Veterans General Hospital, Taichung, TaiwanRheumatology and Immunology Center, China Medical University Hospital, Taichung, TaiwanCollege of Medicine, China Medical University, Taichung, TaiwanPh.D. Program in Translational Medicine and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, TaiwanRheumatology and Immunology Center, China Medical University Hospital, Taichung, TaiwanCollege of Medicine, China Medical University, Taichung, TaiwanCollege of Medicine, China Medical University, Taichung, TaiwanDivision of Infection, China Medical University Hospital, Taichung, TaiwanRheumatology and Immunology Center, China Medical University Hospital, Taichung, TaiwanCollege of Medicine, China Medical University, Taichung, TaiwanTranslational Medicine Laboratory, Rheumatology and Immunology Center, Taichung, TaiwanPh.D. Program in Translational Medicine and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, TaiwanObjectiveNeutralizing anti-interferon (IFN)-γ autoantibodies are linked to opportunistic infections (OIs). To explore the association between anti-IFN-γ autoantibodies and OIs in patients with adult-onset Still's disease (AOSD), we aimed to examine the ability of these autoantibodies to blockade signal transducer and activator of transcription (STAT1)-phosphorylation and chemokines production.MethodsSerum titers of anti-IFN-γ autoantibodies were quantified using ELISA in 29 AOSD and 22 healthy controls (HC). The detectable autoantibodies were verified with immunoblotting assay, and their neutralizing capacity against IFN-γ-signaling was evaluated with flow-cytometry analysis and immunoblotting. IFN-γ-mediated production of supernatant chemokines, including monocyte chemoattractant protein-1 (MCP-1) and IFN-γ inducible protein-10 (IP-10), were measured by ELISA.ResultsAmong 29 AOSD patients, high titers of anti-IFN-γ neutralizing autoantibodies were detectable in two patients with OIs. Immunoblotting assay revealed more effective inhibition of STAT1-phosphorylation in THP-1 cells treated with sera from autoantibody-positive AOSD patients (56.7 ± 34.79%) compared with those from HC (104.3 ±29.51%), which was also demonstrated in flow-cytometry analysis (47.13 ± 40.99 vs. 97.92 ± 9.48%, p < 0.05). Depleted serum IgG from anti-IFN-γ autoAbs-positive AOSD patients with OIs restored phosphorylated STAT-1 upon IFN-γ treatment. Sera from autoantibody-positive AOSD patients more effectively inhibited IFN-γ-mediated production of MCP-1 (45.65 pg/ml) and IP-10 (22.44 pg/ml) than sera from HC (263.1 pg/ml and 104.0 pg/ml, both p < 0.05). Serum samples showing the strongest inhibition of IFN-γ-signaling were from two patients with high-titer autoantibodies and OIs.ConclusionAOSD patients have a high positive rate and titers of anti-IFN-γ autoantibodies. The remarkable blockade effect of high-titer autoantibodies on IFN-γ-mediated STAT1-phosphorylation and chemokines could make these patients susceptible to OIs.https://www.frontiersin.org/articles/10.3389/fmed.2022.1097514/fullanti-interferon-γ autoantibodiesopportunistic infectionsMCP-1IFN-γ inducible protein-10 (IP-10)adult onset Still's disease (AOSD) |
| spellingShingle | Po-Ku Chen Po-Ku Chen Po-Ku Chen Tsai-Ling Liao Tsai-Ling Liao Shih-Hsin Chang Shih-Hsin Chang Shih-Hsin Chang Kai-Jieh Yeo Kai-Jieh Yeo Chia-Hui Chou Chia-Hui Chou Der-Yuan Chen Der-Yuan Chen Der-Yuan Chen Der-Yuan Chen High-titer anti-interferon-γ neutralizing autoantibodies linked to opportunistic infections in patients with adult-onset still's disease Frontiers in Medicine anti-interferon-γ autoantibodies opportunistic infections MCP-1 IFN-γ inducible protein-10 (IP-10) adult onset Still's disease (AOSD) |
| title | High-titer anti-interferon-γ neutralizing autoantibodies linked to opportunistic infections in patients with adult-onset still's disease |
| title_full | High-titer anti-interferon-γ neutralizing autoantibodies linked to opportunistic infections in patients with adult-onset still's disease |
| title_fullStr | High-titer anti-interferon-γ neutralizing autoantibodies linked to opportunistic infections in patients with adult-onset still's disease |
| title_full_unstemmed | High-titer anti-interferon-γ neutralizing autoantibodies linked to opportunistic infections in patients with adult-onset still's disease |
| title_short | High-titer anti-interferon-γ neutralizing autoantibodies linked to opportunistic infections in patients with adult-onset still's disease |
| title_sort | high titer anti interferon γ neutralizing autoantibodies linked to opportunistic infections in patients with adult onset still s disease |
| topic | anti-interferon-γ autoantibodies opportunistic infections MCP-1 IFN-γ inducible protein-10 (IP-10) adult onset Still's disease (AOSD) |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2022.1097514/full |
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