Myasthenia gravis (MG) is a chronic humoral immunity–mediated autoimmune disorder of the neuromuscular junction characterized by muscle weakness. Follicular helper T (Tfh) cells may be the key Th cell subset that promotes MG development, as their major function is helping B cell activation and Ab production. Aberrance of thymus-derived Tfh cells might be implicated in autoimmune diseases including MG; just how circulating Tfh cells, especially those from patients with a normal thymus, contribute to MG pathogenesis remains to be uncovered. In this article, we characterize a population of circulating CD4⁺CXCR5⁺PD-1⁺ Tfh cells in ocular and generalized MG patients without thymic abnormalities and demonstrate that the circulating Tfh cells are significantly enriched in generalized MG patients but not in ocular MG patients compared with healthy subjects, whereas a proportion of follicular regulatory T cells decreased in MG patients. In addition, the frequency of plasma cells and B cells was higher and the serum levels of IL-6/IL-21 were also elevated in these MG patients. The activated Tfh1 and Tfh17 in Tfh cells are the major source for IL-21 production in MG patients. A strong correlation between Tfh cells and the plasma cell frequency and anti–acetylcholine receptor Ab titers was evident in generalized MG patients. In particular, we found that Tfh cells derived from MG patients promoted B cells to produce Abs in an IL-21 signaling–dependent manner. Collectively, our results suggest that circulating Tfh cells may act on autoreactive B cells and thus contribute to the development of MG in patients without thymic abnormalities.

Cerebral small vessel disease (CSVD) is one of the main causes of vascular dementia in older individuals. Apart from risk containment, efforts to prevent or treat CSVD are ineffective due to the unknown pathogenesis of the disease. CSVD, a subtype of stroke, is characterized by recurrent strokes and neurodegeneration. Blood–brain barrier (BBB) impairment, chronic inflammatory responses, and leukocyte infiltration are classical pathological features of CSVD. Understanding how BBB disruption instigates inflammatory and degenerative processes may be informative for CSVD therapy. Antigens derived from the brain are found in the peripheral blood of lacunar stroke patients, and antibodies and sensitized T cells against brain antigens are also detected in patients with leukoaraiosis. These findings suggest that antigen-specific immune responses could occur in CSVD. This review describes the neurovascular unit features of CSVD, the immune responses to specific neuronal and glial processes that may be involved in a distinct mechanism of CSVD, and the current evidence of the association between mechanisms of inflammation and interventions in CSVD. We suggest that autoimmune activity should be assessed in future studies; this knowledge would benefit the development of effective therapeutic interventions in CSVD.

We characterized a unique group of patients with neuromyelitis optica spectrum disorder (NMOSD) who carried autoantibodies of aquaporin-4 (AQP4) and myelin-oligodendrocyte glycoprotein (MOG). Among the 125 NMOSD patients, 10 (8.0%) were AQP4- and MOG-ab double positive, and 14 (11.2%) were MOG-ab single positive. The double-positive patients had a multiphase disease course with a high annual relapse rate (P=0.0431), and severe residual disability (P>0.0001). Of the double- positive patients, 70% had MS-like brain lesions, more severe edematous, multifocal regions on spinal magnetic resonance imaging (MRI), pronounced decreases of retinal nerve fiber layer thickness and atrophy of optic nerves. In contrast, patients with only MOG-ab had a higher ratio of monophasic disease course and mild residual disability. Spinal cord MRI illustrated multifocal cord lesions with mild edema, and brain MRIs showed more lesions around lateral ventricles. NMOSD patients carrying both autoantibodies to AQP4 and MOG existed and exhibited combined features of prototypic NMO and relapsing- remitting form of MS, whereas NMOSD with antibodies to MOG only exhibited an “intermediate” phenotype between NMOSD and MS. Our study suggests that antibodies against MOG might be pathogenic in NMOSD patients and that determination of anti-MOG antibodies maybe instructive for management of NMOSD patients.

Myasthenia gravis (MG) and neuromyelitis optica (NMO) are autoimmune channelopathies of the peripheral neuromuscular junction (NMJ) and central nervous system (CNS) that are mainly mediated by humoral immunity against the acetylcholine receptor (AChR) and aquaporin-4 (AQP4), respectively. The diseases share some common features, including genetic predispositions, environmental factors, the breakdown of tolerance, the collaboration of T cells and B cells, imbalances in T helper 1 (Th1)/Th2/Th17/regulatory T cells, aberrant cytokine and antibody secretion, and complement system activation. However, some aspects of the immune mechanisms are unique. Both targets (AChR and AQP4) are expressed in the periphery and CNS, but MG mainly affects the NMJ in the periphery outside of CNS, whereas NMO preferentially involves the CNS. Inflammatory cells, including B cells and macrophages, often infiltrate the thymus but not the target—muscle in MG, whereas the infiltration of inflammatory cells, mainly polymorphonuclear leukocytes and macrophages, in NMO, is always observed in the target organ—the spinal cord. A review of the common and discrepant characteristics of these two autoimmune channelopathies may expand our understanding of the pathogenic mechanism of both disorders and assist in the development of proper treatments in the future.

Ischemic stroke induces profound effects on the peripheral immune system, which may participate the infectious complications. However, the exact function and mechanism of immune reaction in stroke development are not well-elucidated. Recently, several long non-coding RNAs (LncRNAs) are reported to affect ischemic stroke process, especially the immunological response after stroke. In the present study, we investigated the profile of LncRNAs in human ischemic stroke during the transition from the acute to subacute stage, when the state of the peripheral immune system changes from activation to systemic immunosuppression. In this study, we analyzed the RNA-sequencing (RNA-seq) datasets obtained at two time points (24 h and 7 days) from the peripheral blood mononuclear cells of ischemic patients. Vascular risk factor-matched healthy adults were enrolled as controls. A total of 3,009 LncRNAs and 3,982 mRNAs were identified as differentially expressed 24 h after stroke. Furthermore, 2,034 LncRNAs and 1,641 mRNAs were detected to be differentially expressed on day 7. Bioinformatics analyses, including GO, KEGG pathway enrichment analysis, and network analysis, were performed for the identified dysregulated genes. Our study reveals that ischemic stroke can influence the expression of LncRNAs and mRNAs in the peripheral blood at both the acute and subacute stages; the level of LncRNAs in the antigen processing and presentation pathway was clearly upregulated at 24 h and had recovered to normal levels on day 7 after stroke. Moreover, inflammatory mediator regulation of TRP channels and GABAergic synapses were two specifically downregulated pathways on day 7 after stroke. Our findings provide a valuable resource for further study of the role of LncRNAs in peripheral immune system changes following ischemic stroke.