Salaman M R, Isenberg D A
1 Department of Medicine, St Mary's Campus, Imperial College, London, UK.
2 Centre for Rheumatology, University College London, London, UK.
Lupus. 2017 Dec;26(14):1513-1516. doi: 10.1177/0961203317707826. Epub 2017 May 23.
Immunological abnormalities seen in relatives of patients with autoimmune disorders can be useful in understanding the pathogenesis of the disease since, unlike in patients, they cannot result from the disease process or drug treatment. In this article we present a brief overview of our studies of the basic immunological status of close relatives of SLE patients. We looked at blood levels of IgG, IgM and antibodies to double-stranded DNA, as well as at NK cell numbers and cytotoxic activity and the levels of NKT, B and T cells. As many as 60% of relatives showed one or more abnormalities in these assays. Most notably there were increased levels of IgG in male and female relatives and a reduction of IgM in females. IgG correlated inversely with NKT cell numbers adding strength to the concept that the presence of IgG autoantibodies in patients is due to impaired regulation by NKT cells. IgM, on the other hand, correlated inversely with NK cells which may thus have a role in bringing about the reduced IgM seen in some patients. Immunological abnormalities were found to be more often associated with parents and offspring of patients than with their siblings, pointing to the involvement of environmental or epigenetic influences in lupus pathogenesis.
自身免疫性疾病患者亲属中出现的免疫异常有助于理解该疾病的发病机制,因为与患者不同,这些异常并非由疾病进程或药物治疗引起。在本文中,我们简要概述了对系统性红斑狼疮(SLE)患者近亲基本免疫状态的研究。我们检测了血液中IgG、IgM以及双链DNA抗体的水平,还检测了自然杀伤(NK)细胞数量、细胞毒性活性以及自然杀伤T(NKT)细胞、B细胞和T细胞的水平。在这些检测中,多达60%的亲属表现出一种或多种异常。最显著的是,男性和女性亲属的IgG水平均升高,而女性亲属的IgM水平降低。IgG与NKT细胞数量呈负相关,这进一步支持了患者体内IgG自身抗体的存在是由于NKT细胞调节受损这一观点。另一方面,IgM与NK细胞呈负相关,因此NK细胞可能在导致部分患者IgM降低方面发挥作用。研究发现,免疫异常在患者的父母和后代中比在其兄弟姐妹中更常见,这表明环境或表观遗传因素参与了狼疮的发病机制。