| Title: | Circulating plasmablasts contribute to antiphospholipid antibody production, associated with type I interferon upregulation |
| Authors: | Hisada, Ryo Browse this author |
| Kato, Masaru Browse this author →KAKEN DB |
| Sugawara, Eri Browse this author |
| Kanda, Masatoshi Browse this author |
| Fujieda, Yuichiro Browse this author →KAKEN DB |
| Oku, Kenji Browse this author →KAKEN DB |
| Bohgaki, Toshiyuki Browse this author →KAKEN DB |
| Amengual, Olga Browse this author →KAKEN DB |
| Horita, Tetsuya Browse this author →KAKEN DB |
| Yasuda, Shinsuke Browse this author →KAKEN DB |
| Atsumi, Tatsuya Browse this author →KAKEN DB |
| Keywords: | antiphospholipid antibody |
| antiphospholipid syndrome |
| B-lymphocytes |
| interferon type i |
| polymorphism |
| single nucleotide |
| Issue Date: | 30-Jul-2019 |
| Publisher: | John Wiley & Sons |
| Journal Title: | Journal of thrombosis and haemostasis |
| Volume: | 17 |
| Issue: | 7 |
| Start Page: | 1134 |
| End Page: | 1143 |
| Publisher DOI: | 10.1111/jth.14427 |
| PMID: | 30864219 |
| Abstract: | Essentials The mechanism of antiphospholipid antibodies (aPL) production remains unclear. We investigated lymphocyte subset, single nucleotide polymorphisms (SNP), and aPL-producing cells. The increase of circulating plasmablasts was associated with type I interferon upregulation. Our novel ex vivo assay revealed circulating plasmablasts as a major source of aPL. Background/objective Antiphospholipid antibodies (aPL) are pathogenic autoantibodies in antiphospholipid syndrome (APS). This study aimed to clarify the mechanism of aPL production. Methods T cell and B cell subsets were evaluated in peripheral blood mononuclear cells (PBMCs) of 26 primary APS (PAPS), 19 systemic lupus erythematosus-associated APS (SLE/APS) patients and 10 healthy controls. The SLE-related or APS-related single nucleotide polymorphisms (SNP) were analyzed in those patients. Interferon (IFN) score was calculated based on the mRNA expression of Ly6e, Mx1, IFIT1, and IFIT3 in PBMCs. The PBMCs obtained from APS patients were cultured ex vivo following depletion of CD20 positive or negative B cells and the culture supernatants were applied to aPL measurements. Results In PAPS and SLE/APS patients, Th2, Th17, and plasmablasts were increased while regulatory T, memory B, and regulatory B cells were decreased compared to healthy controls. Genetic analysis revealed that the increase of plasmablasts was more pronounced in patients carrying a risk allele of toll like receptor (TLR) 7 SNP rs3853839. The IFN score was significantly higher in the risk allele carriers. Ex vivo experiments showed that aPL were present in the culture supernatant of PBMCs lacking CD20+CD19+ subset, but not in that of cells lacking CD20-CD19+ subset. Conclusions Our data indicate an important role of plasmablasts in the production of aPL. Furthermore, the increase of plasmablasts was associated with TLR 7 and type I IFN, suggesting a common pathophysiology in SLE and APS. Targeting plasmablasts might be a novel immunological therapeutic approach in the treatment of APS. |
| Rights: | This is the peer reviewed version of the following article: Journal of Thrombosis and Haemostasis: 17(7): 1134-1143, which has been published in final form at https://doi.org/10.1111/jth.14427. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/78965 |
| Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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