与银屑病关节炎患者和健康供体相比，类风湿关节炎患者中表达功能活跃的NKG2A的自然杀伤细胞水平升高。

Functionally active NKG2A-expressing natural killer cells are elevated in rheumatoid arthritis patients compared to psoriatic arthritis patients and healthy donors.

作者信息

van Bijnen S T A, Cossu M, Roeven M W H, Jansen T L, Preijers F, Spanholtz J, Dolstra H, Radstake T R D J

机构信息

Department of Hematology, and Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands.

Dept.of Rheumatology, Clinical Immunology and Lab. of Translational Immunology, University Medical Center Utrecht, The Netherlands; and Referral Center for Systemic Autoimmune Dis., Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

出版信息

Clin Exp Rheumatol. 2015 Nov-Dec;33(6):795-804. Epub 2015 Sep 28.

PMID:26411696

Abstract

OBJECTIVES

Natural killer cell receptors (NKR) have been implicated in rheumatoid (RA) and psoriatic arthritis (PsA) pathogenesis. To gain more insight into their role, we characterised NKR (co-)expression patterns on NK and T cells and NK cell function in RA and PsA.

METHODS

The frequency of NK and T cells expressing killer like immunoglobulin (KIR) and NKG2 receptors and natural cytotoxicity receptors was assessed by 10-colour flow cytometry in peripheral blood of 23 RA, 12 PsA patients and 18 healthy donors (HD). NK cell cytotoxicity and IFN-gamma production was assessed in 8 RA patients and 8 HD.

RESULTS

In RA but not PsA, the frequency of NK cells (median; range) expressing NKG2A (42%; 14-81%) was elevated compared to HD (23%; 9-58%). NKG2A⁺ NK cells predominantly lack KIR, but display normal cytotoxicity and IFN-γ production. In contrast, RA patients with normal NKG2A⁺ NK cell frequency have less functional NK cells compared to HD. T cells expressing Fc-gamma receptor CD16 were elevated in RA (median 0.75%) versus HD (0.3%). Furthermore, T cells expressing the KIRs CD158ah in both RA (0.7%) and PsA (0.3%), and CD158e1e2 in RA (1.5%) were elevated compared to HD (0.2% and 0.4%, respectively). In RA, CD4⁺ T cells expressing the KIRs CD158ah, CD158b1b2j and CD158e1e2 were low (<2%) but significantly elevated compared to HD.

CONCLUSIONS

This study demonstrates the presence of an elevated, functionally active NKG2A⁺ KIR- NK cell population in RA. Together with an elevated frequency of NKR-expressing T cells, these changes may reflect differential pathogenetic involvement.

摘要

目的

自然杀伤细胞受体（NKR）已被证实与类风湿关节炎（RA）和银屑病关节炎（PsA）的发病机制有关。为了更深入了解它们的作用，我们对RA和PsA患者中NK细胞和T细胞上NKR的（共）表达模式以及NK细胞功能进行了特征分析。

方法

通过10色流式细胞术评估23例RA患者、12例PsA患者和18名健康供者（HD）外周血中表达杀伤细胞免疫球蛋白样受体（KIR）和NKG2受体以及自然细胞毒性受体的NK细胞和T细胞的频率。对8例RA患者和8名HD的NK细胞细胞毒性和干扰素-γ产生情况进行了评估。

结果

与HD（23%；9%-58%）相比，RA患者中表达NKG2A的NK细胞频率（中位数；范围）升高（42%；14%-81%），而PsA患者中未出现这种情况。NKG2A⁺NK细胞主要缺乏KIR，但具有正常的细胞毒性和干扰素-γ产生能力。相比之下，NKG2A⁺NK细胞频率正常的RA患者与HD相比，功能性NK细胞较少。表达Fc-γ受体CD16的T细胞在RA患者中（中位数0.75%）高于HD（0.3%）。此外，与HD（分别为0.2%和0.4%）相比，RA（0.7%）和PsA（0.3%）中表达KIR CD158ah的T细胞以及RA（1.5%）中表达CD158e1e2的T细胞均升高。在RA中，表达KIR CD158ah、CD158b1b2j和CD158e1e2的CD4⁺T细胞比例较低（<2%），但与HD相比显著升高。