PMID- 36698819
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230202
IS  - 2296-858X (Print)
IS  - 2296-858X (Electronic)
IS  - 2296-858X (Linking)
VI  - 9
DP  - 2022
TI  - High-titer anti-interferon-gamma neutralizing autoantibodies linked to opportunistic 
      infections in patients with adult-onset still's disease.
PG  - 1097514
LID - 10.3389/fmed.2022.1097514 [doi]
LID - 1097514
AB  - OBJECTIVE: Neutralizing anti-interferon (IFN)-gamma autoantibodies are linked to 
      opportunistic infections (OIs). To explore the association between anti-IFN-gamma 
      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. METHODS: Serum titers of anti-IFN-gamma 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-gamma-signaling was evaluated with flow-cytometry analysis and 
      immunoblotting. IFN-gamma-mediated production of supernatant chemokines, including 
      monocyte chemoattractant protein-1 (MCP-1) and IFN-gamma inducible protein-10 
      (IP-10), were measured by ELISA. RESULTS: Among 29 AOSD patients, high titers of 
      anti-IFN-gamma 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-gamma autoAbs-positive AOSD patients with OIs restored 
      phosphorylated STAT-1 upon IFN-gamma treatment. Sera from autoantibody-positive AOSD 
      patients more effectively inhibited IFN-gamma-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-gamma-signaling 
      were from two patients with high-titer autoantibodies and OIs. CONCLUSION: AOSD 
      patients have a high positive rate and titers of anti-IFN-gamma autoantibodies. The 
      remarkable blockade effect of high-titer autoantibodies on IFN-gamma-mediated 
      STAT1-phosphorylation and chemokines could make these patients susceptible to 
      OIs.
CI  - Copyright (c) 2023 Chen, Liao, Chang, Yeo, Chou and Chen.
FAU - Chen, Po-Ku
AU  - Chen PK
AD  - Rheumatology and Immunology Center, China Medical University Hospital, Taichung, 
      Taiwan.
AD  - College of Medicine, China Medical University, Taichung, Taiwan.
AD  - Translational Medicine Laboratory, Rheumatology and Immunology Center, Taichung, 
      Taiwan.
FAU - Liao, Tsai-Ling
AU  - Liao TL
AD  - Ph.D. Program in Translational Medicine and Rong Hsing Research Center for 
      Translational Medicine, National Chung Hsing University, Taichung, Taiwan.
AD  - Department of Medical Research, Taichung Veterans General Hospital, Taichung, 
      Taiwan.
FAU - Chang, Shih-Hsin
AU  - Chang SH
AD  - Rheumatology and Immunology Center, China Medical University Hospital, Taichung, 
      Taiwan.
AD  - College of Medicine, China Medical University, Taichung, Taiwan.
AD  - Ph.D. Program in Translational Medicine and Rong Hsing Research Center for 
      Translational Medicine, National Chung Hsing University, Taichung, Taiwan.
FAU - Yeo, Kai-Jieh
AU  - Yeo KJ
AD  - Rheumatology and Immunology Center, China Medical University Hospital, Taichung, 
      Taiwan.
AD  - College of Medicine, China Medical University, Taichung, Taiwan.
FAU - Chou, Chia-Hui
AU  - Chou CH
AD  - College of Medicine, China Medical University, Taichung, Taiwan.
AD  - Division of Infection, China Medical University Hospital, Taichung, Taiwan.
FAU - Chen, Der-Yuan
AU  - Chen DY
AD  - Rheumatology and Immunology Center, China Medical University Hospital, Taichung, 
      Taiwan.
AD  - College of Medicine, China Medical University, Taichung, Taiwan.
AD  - Translational Medicine Laboratory, Rheumatology and Immunology Center, Taichung, 
      Taiwan.
AD  - Ph.D. Program in Translational Medicine and Rong Hsing Research Center for 
      Translational Medicine, National Chung Hsing University, Taichung, Taiwan.
LA  - eng
PT  - Journal Article
DEP - 20230109
PL  - Switzerland
TA  - Front Med (Lausanne)
JT  - Frontiers in medicine
JID - 101648047
PMC - PMC9868624
OTO - NOTNLM
OT  - IFN-gamma inducible protein-10 (IP-10)
OT  - MCP-1
OT  - adult onset Still's disease (AOSD)
OT  - anti-interferon-gamma autoantibodies
OT  - opportunistic infections
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/01/27 06:00
MHDA- 2023/01/27 06:01
PMCR- 2023/01/09
CRDT- 2023/01/26 02:39
PHST- 2022/11/14 00:00 [received]
PHST- 2022/12/20 00:00 [accepted]
PHST- 2023/01/26 02:39 [entrez]
PHST- 2023/01/27 06:00 [pubmed]
PHST- 2023/01/27 06:01 [medline]
PHST- 2023/01/09 00:00 [pmc-release]
AID - 10.3389/fmed.2022.1097514 [doi]
PST - epublish
SO  - Front Med (Lausanne). 2023 Jan 9;9:1097514. doi: 10.3389/fmed.2022.1097514. 
      eCollection 2022.