甲状腺相关眼病免疫相关发病机制的研究现状与进展

甲状腺相关眼病（thyroid associated ophthalmopathy，TAO）是Graves病最常见的甲状腺腺外表现，主要表现为上眼睑退缩、水肿、眶周组织红斑和眼球突出，进一步发展可影响患者视力甚至导致失明。TAO的发病机制不完全清楚，由多种因素共同影响，但是目前患者自身免疫的功能异常是TAO的主要发病因素。本文将从细胞免疫、自身抗原和自噬这几个方面阐述TAO免疫相关发病机制研究的现状与进展，为临床工作和相关研究提供参考。     

Immune cell trafficking to the islets during type 1 diabetes

Inhibition of immune cell trafficking to the pancreatic islets during type 1 diabetes (T1D) has therapeutic potential, since targeting of T cell and B cell trafficking has been clinically effective in other autoimmune diseases. Trafficking to the islets is characterized by redundancy in adhesion molecule and chemokine usage, which has not enabled effective targeting to date. Additionally, cognate antigen is not consistently required for T cell entry into the islets throughout the progression of disease. However, myeloid cells are required to enable T cell and B cell entry into the islets, and may serve as a convergence point in the pathways controlling this process. In this review we describe current knowledge of the factors that mediate immune cell trafficking to pancreatic islets during T1D progression.     

Co-occurrence of IgE and IgG autoantibodies in patients with chronic spontaneous urticaria

Chronic spontaneous urticaria (CSU) pathogenesis shows a complex and still unclear interplay between immunoglobulin (Ig)G- and IgE-mediated autoimmunity, leading to mast cell and basophil degranulation and wheal formation. The objective of this study was to evaluate at the same time IgE- and IgG-reactivity to well recognized and recently reported autoantigens in CSU patients, and to assess the effects of such reactivity on response to the anti-IgE monoclonal antibody omalizumab. Twenty CSU patients underwent omalizumab treatment. Urticaria activity score 7 (UAS7) was recorded at baseline and at different drug administration time-points for categorizing early-, late- or non-responders. At baseline, sera from the 20 patients and from 20 controls were tested for IgE and IgG autoantibodies to high- and low-affinity IgE receptors (FcεRI and FcεRII), tissue factor (TF) and thyroglobulin (TG) by immunoenzymatic methods. Antibody levels were compared with those of controls and analysed according to response. Eighteen patients were omalizumab responders (11 early and seven late), while two were non-responders. More than 50% of patients had contemporary IgE and IgG to at least to one of the four different autoantigens. Late responders showed higher levels of both anti-TF IgE and IgG than early responders (P = 0·011 and P = 0·035, respectively). Twenty-five per cent of patients had levels of anti-FcεRI IgE, exceeding the upper normal limit, suggesting that it could be a novel auto-allergen in CSU. In CSU, there is an autoimmune milieu characterized by the co-existence of IgE and IgG autoantibodies to the same antigen/allergen, particularly in late responders to omalizumab, possibly explaining the slower response.     

A novel human STAT3 mutation presents with autoimmunity involving Th17 hyperactivation

Mutations in STAT3 have recently been shown to cause autoimmune diseases through increased lymphoproliferation. We describe a novel Pro471Arg STAT3 mutation in a patient with multiple autoimmune diseases, causing hyperactivation of the Th17 pathway. We show that IL-17 production by primary T cells was enhanced and could not be further increased by IL-6, while IL-10 reduced Th17 cell numbers. Moreover, specific inhibition of STAT3 activation resulted in diminished IL-17 production. We show that the Pro471Arg STAT3 mutation yields both increased levels of IgA and IgG, probably due to high IL-21 levels. When remission was reached through medical intervention, IL-17 levels normalized and the clinical symptoms improved, supporting the idea that STAT3 gain-of-function mutations can cause hyperactivation of the Th17 pathway and thereby contribute to autoimmunity.