Serum amyloid A facilitates expansion of CD4+ T cell and CD19+ B cell subsets implicated in the severity of myasthenia gravis patients.

Serum amyloid A (SAA) is a clinically useful inflammatory marker involved in the pathogenesis of autoimmune diseases. This study aimed to explore the SAA levels in a cohort of patients with myasthenia gravis (MG) in relation to disease-related clinical parameters and myasthenic crisis (MC) and elucidate the effects of SAA on immune response. A total of 82 MG patients including 50 new-onset MG patients and 32 MC patients were enrolled in this study. Baseline data and laboratory parameters of all enrolled MG patients were routinely recorded through electronic medical systems. SAA levels were measured by enzyme-linked immunosorbent assay (ELISA) kit. CD4+ T and CD19+ B cell subsets were analyzed by flow cytometry. In vitro, human recombinant SAA (Apo-SAA) was applied to stimulate peripheral blood mononuclear cells (PBMCs) from MG patients to observe the effect on T and B cell differentiation. Our results indicated that SAA levels in new-onset MG patients were higher than those in controls and were positively correlated with QMG score, MGFA classification, plasmablast cells, IL-6, and IL-17 levels. Subgroup analysis revealed that SAA levels were increased in generalized MG (GMG) patients than in ocular MG (OMG), as well as elevated in late-onset MG (LOMG) than in early-onset MG (EOMG) and higher in MGFA III/IV compared with MGFA I/II. The ROC curve demonstrated that SAA showed good diagnostic value for MC, especially when combined with NLR. In vitro, Apo-SAA promoted the Th1 cells, Th17 cells, plasmablast cells, and plasma cells differentiation in MG PBMCs. The present findings suggested that SAA was increased in MG patients and promoted expansion of CD4+ T cell and CD19+ B cell subsets, which implicated in the severity of MG patients.

Serum neurofilament light chain predicts spinal cord atrophy in neuromyelitis optica spectrum disorder.

Levels of serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) are useful biomarkers of disease activity and disability in neuromyelitis optica spectrum disorder (NMOSD). Here we investigated the association of sNfL and sGFAP levels with brain and spinal cord volumes in patients with NMOSD. Fifteen patients with NMOSD were enrolled in this prospective study. The median baseline level of sNfL was 42.2 (IQR, 16.1-72.6) pg/mL and decreased to 8.5 (IQR, 7.4-16.6) pg/mL at the end of the study. The reduction in sNfL was associated with a 7.5% loss of cervical spinal cord volume (CSCV) (p = 0.001). The levels of sGFAP reduced from 239.2 (IQR, 139.0-3393.3) pg/mL at baseline to 108.5 (IQR, 74.2-154.6) pg/mL. However, there was no strong correlation between sGFAP levels and CSCV changes during the follow-up period. Our data suggested that sNfL level is a useful biomarker for predicting spinal cord atrophy in patients with NMOSD.

Rituximab induces a transient fluctuation of peripheral and follicular helper T cells in neuromyelitis optica spectrum disorder.

Autoreactive CD4+ helper T cells are implicated in the pathogenesis of neuromyelitis optica spectrum disorder (NMOSD). Both PD-1+CXCR5+CD4+ T follicular helper (Tfh) cells and PD-1+CXCR5-CD4+ T peripheral helper (Tph) cells can contribute to B-cell immune responses and the production of antibodies. Here we show the effect of B-cell depletion with rituximab on the homeostasis of Tfh cells, Tph cells and their subsets in patients with NMOSD. After rituximab treatment, total Tph cells, total Tfh cells, Tph17 cells, Tph17.1 cells, Tph1 cells, and Tfh1 cells tended to decrease at month 1, but gradually increased at month 6 and restored at month 12. Besides, Tph17.1 cells and Tfh17.1 cells were correlated with the proportion of CD19- antibody-secreting cells. Our data suggest that rituximab induced a fluctuation of proinflammatory Tph and Tfh subsets within one year after initiation of the treatment.