Increased CEACAM1 expression on peripheral blood neutrophils in patients with rheumatoid arthritis

Abstract

Altered expression of adhesion molecules in immune cells has been demonstrated in rheumatoid arthritis (RA). Carcinoembryonic–antigen–related cell–adhesion molecule 1 (CEACAM1) is an adhesion molecule that acts as a coinhibitory receptor in the immune system. We investigated the role of CEACAM1 in immune cell subsets of patients with RA. Peripheral blood was obtained from 37 patients with RA and 20 healthy controls (HC). The expression of CEACAM1 and T–cell immunoglobulin mucin domain molecule (TIM) –3 on peripheral blood mononuclear cells and neutrophils was analyzed by flow cytometry. Intracellular TIM–3 expression was analyzed using cellular lysates by Western blot analysis. Serum levels of soluble CEACAM1 (sCEACAM1) were estimated by an enzyme-linked immunosorbent assay. CEACAM1 expression was not detected in peripheral blood mononuclear cells, including in CD14(+) monocytes and CD3(+) lymphocytes isolated from patients with RA or HC. However, substantial cell–surface expression of CEACAM1 was detected in peripheral blood neutrophils, and it was significantly elevated in samples from patients with RA without remission compared to those in remission. There was no significant difference in serum levels of sCEACAM1 between patients with RA and HC. Cell-surface expression of TIM-3 was not detected in peripheral blood neutrophils from patients with RA or HC but was seen in CD14(+) monocytes. However, there was no significant difference in TIM–3 expression on monocytes between patients with RA and HC. Our data indicate that cell-surface expression of CEACAM1 on peripheral blood neutrophils are higher in patients with RA and that it is associated with rheumatoid inflammation. Further studies are needed to explore the potential role of CEACAM1 in rheumatoid inflammatory pathways.

Inhibition of CEACAM1 expression in cytokine-activated neutrophils using JAK inhibitors

“…CEACAM1 has been shown to be upregulated in in ammatory responses [16]. Indeed, we previously reported the increased expression levels of CEACAM1 in neutrophils isolated from patients with active RA [5]. In rheumatoid neutrophils, CEACAM1 expression could be induced by in ammatory cytokines, including TNF-α, an essential cytokine in the pathogenesis of RA [17].…”

“…In the rheumatoid synovium, neutrophils in ltrating synovial membranes or uids play an important role in the pathogenesis of RA [4]. We previously reported that CEACAM1 is selectively expressed in neutrophils not in T cells or monocytes, upregulated in peripheral blood neutrophils isolated from patients with active RA [5]. This observation suggests that in ammatory stimuli induce upregulation of the CEACAM1 gene on neutrophils in patients with active RA.…”

Recent advances on neutrophil dysregulation in the pathogenesis of rheumatic diseases

“…Matsumoto et al reported that CEA-CAM1 was exclusively expressed on peripheral blood neutrophils in RA patients. In addition, the expression levels of CEACAM1 in RA neutrophils were associated with rheumatoid inflammation [25].…”

第504回福島医学会学術研究集会抄録

“…，西森 克彦 1) ，水野 景太2) 前島 裕子1) ，下村 健寿1) ① 確率論では p MI = exp(−MI) , MI = −log(p MI ) が成立する。② 統計学では，サンプルサイズを N とすると， p N･MI = exp(−N･MI) , MI = −log(p N･MI ) /N が成立する。 2) 確率変数分布が既知の場合，フィッシャー正 確確率 P F について，③ MI = −log(P F ) /N が漸近 的に成立する。 以上 ① -③ は情報理論と確率統計学の統合を導 く新定理であり，両体系の手法を同時に適用可能と する。この定理を応用することで，高次元確率変数 間の MI と p 値の高精度定量に基づく，ab initio 遺 伝子軌道法を開発することができた 1 。 【文献】 1. Mori, T., et al Influential force : from Higgs to the novel immune checkpoint KYNU.…”