Immunocompetent Cells Expressing Citrullinated Proteins in Joint Synovium of Osteoarthritis and Rheumatoid Arthritis

Kyoko Honne¹, Masahiro Iwamoto², Shunichiro Hanai¹, Satoshi Machida³, Hitoshi Sekiya⁴, Reina Tsuda⁵, Tatsuhiko Ozawa⁵, Tadayoshi Karasawa⁶, Atsushi Muraguchi⁵, Masafumi Takahashi⁶, Hiroyuki Kishi⁵ and Seiji Minota⁷, ¹Division of Rheumatology and Clinical Immunology, Jichi Medical University, Shimotsuke, Japan, ²Deivision of Rheumatology and Clinical Immunology, Jichi Medical University, Shimotsuke, Japan, ³Department of Orthopaedic Surgery, Orthopedics Clinic Medical Papas, Tochigi, Japan, ⁴Department of orthopedic surgery, Jichi Medical University, Shimotsuke, Japan, ⁵Department of Immunology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan, ⁶Division of Inflammation Research Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Japan, ⁷Division of Rheumatology and Clinical Immunology, Jichi Medical University, Tochigi, Japan

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: anti-CCP antibodies, Macrophage, rheumatoid arthritis (RA) and synovial cells, synovial fluid

Session Information

Date: Sunday, November 5, 2017

Title: Rheumatoid Arthritis – Human Etiology and Pathogenesis Poster I

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: Human monoclonal ACPA (Human-ACPA) is reported to strongly bind to synovium in RA patients [1]. The aims of our study were 1) To investigate whether Human-ACPA, which was generated from peripheral blood B cells from an RA patient by us, binds to synovium from OA and RA, and 2) To identify cell-type expressing citrullinated proteins in synovium from OA and RA patients.

Methods: Human-ACPA was produced by a method published earlier [2,　3]. Joint synovium from OA or RA patients (10 OA, 10 RA) were immunohistochemically stained with Human-ACPA. Double-label immunofluorescence staining with Human-ACPA/CD3, Human-ACPA/CD20 or Human-ACPA/CD68 (3 OA, 3 RA), and confocal laser scanning microscope (3 RA) were performed in the synovia for the images.

Results: Human-ACPA bound to all layers in synovium from RA patients. Human-ACPA positive cells were limited in the surface layer in 7 of 10 OA patients, while no Human-ACPA positive cells were found in the remaining 3 OA synovia.

Human-ACPA positive cells in synovium of OA were not double-stained with CD3, CD20 or CD68 monoclonal antibody. On the other hand, there were Human-ACPA/CD3, Human-ACPA/CD20 or Human-ACPA/CD68 double positive cells in synovium of RA patients.

Most of the ACPA positive cells were stained with CD68. Human-ACPA/CD3 and Human-ACPA/CD20 double positive cells also existed in deeper layers of synovium in RA patients.

Conclusion: All layers of synovium in RA patients were studded with cells which contained citrullinated proteins. Cells positive for citrullinated protein in RA were mainly macrophage-lineage (CD68⁺). Citrullinated protein was also expressed in T cells (CD3⁺) and B cells (CD20⁺) in RA. Citrullinated protein existed in the strip-shaped form only in the surface layer of OA synovia and may have been induced by mechanical stresses. No macrophages, T cells or B cells were positive for citrullinated protein in OA.

[1]Amara K et al. Monoclonal IgG antibodies generated from joint-derived B cells of RA patients have a strong bias toward citrullinated autoantigen recognition. J Exp Med 2014; 210: 445-55.

[2] Jin A et al. A rapid and efficient single-cell manipulation method screening antigen-specific antibody-secreting cells from human peripheral blood. Nat Med 2009; 15: 1088-92

[3]Tsuda et al. Monoclonal antibody citrullinated peptides obtained from rheumatoid arthritis patients reacts with numerous citrullinated microbial and food proteins. Arthritis and Rheumatol 2015; 67: 2020-31

Disclosure: K. Honne, Takeda science fundation, 2; M. Iwamoto, None; S. Hanai, None; S. Machida, None; H. Sekiya, None; R. Tsuda, None; T. Ozawa, None; T. Karasawa, None; A. Muraguchi, None; M. Takahashi, None; H. Kishi, None; S. Minota, None.

To cite this abstract in AMA style:

Honne K, Iwamoto M, Hanai S, Machida S, Sekiya H, Tsuda R, Ozawa T, Karasawa T, Muraguchi A, Takahashi M, Kishi H, Minota S. Immunocompetent Cells Expressing Citrullinated Proteins in Joint Synovium of Osteoarthritis and Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/immunocompetent-cells-expressing-citrullinated-proteins-in-joint-synovium-of-osteoarthritis-and-rheumatoid-arthritis/. Accessed .

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