Novel electrical therapy to improve sleep disturbance in patients with autoimmune rheumatic diseases.

OBJECTIVES: Sleep disturbance is common in autoimmune rheumatism diseases (ARD) and it plays an important role in activating disease and affects the quality of life. This study aims to evaluate the efficacy and acceptability of the novel electrical therapy on sleep disturbance in ARD patients and its effect on immunologic factors. METHODS: A total of 51 ARD patients (26 treatment group and 25 control group) with sleep disturbance were enrolled in this study. Sleep parameters and immunological indicators (serum level of 12 cytokines and immune function) were collected. The novel electrical therapy was prescribed for 15-30 min 3-6 times a day. The Pittsburg Sleep Index (PSQI) was assessed before and after 3 months' treatment by Mi Energy equipment. Immune function and serum levels of cytokines of all participants at baseline and after treatment were tested with flow cytometry and flow immunofluorescence, respectively. Correlation analysis was used to analyze the relationship between sleep disturbance and immunologic factors. Multiple linear regression analysis was employed to investigate the risk of sleep disturbance in ARD. RESULTS: The global score of PSQI (Baseline: 12.81 ± 4.07, After novel electrical therapy: 4.88 ± 2.76) was effectively improved after 3 months of adjuvant therapy by electrical therapy. We also found that serum levels of IL-8 and IL-1ß statistically significantly decreased after novel electrical therapy. This adjuvant therapy can also significantly decrease the percentage of CD4 + CD8 + T cell, effector memory CD8 + T cell, Memory CD8 + T cell, Th17 cell, and plasma cell and significantly can increase the percentage of naïve CD8 + T cell, Th2 cell, and Tfh2 cell. Nevertheless, all serum level of 12 cytokines and the percentage of immune cells did not correlate with the PSQI global score except the Tc17 cell. Furthermore, age is an independent risk factor influencing PSQI scores (OR = 1.15, p < 0.05) in patients with autoimmune diseases through multiple linear regression analysis. CONCLUSIONS: Novel electrical therapy can effectively improve sleep disturbance in patients with ARD. It can also change the serum level of some cytokines (IL-8 and IL-1ß) and percentage of immune cells (CD4 + CD8 + T cell, effector memory CD8 + T cell, Memory CD8 + T cell, Th17 cell, naïve CD8 + T cell, Th2 cell, Tfh2 cell, and plasma cell).

Peripheral CD4+ /CD8+ T cell composition distinct from healthy individuals is shared by ankylosing spondylitis and rheumatoid arthritis.

OBJECTIVE: Ankylosing spondylitis (AS) and rheumatoid arthritis (RA) are chronic inflammatory joint diseases, linking to the alterations of immune cells. We attempted to assess whether the alterations in the composition of CD4+ /CD8+ T cells are different between AS and RA and identify the characteristic cells between male and female patients. METHODS: The proportions of CD3+ or double positive T cells, 6 CD4+ T subsets and 9 CD8+ T cell subsets were detected by flow cytometry and compared in 30 healthy individuals, 42 AS patients and 45 RA patients. The differentially altered cells were individually analyzed for associations with disease activity parameters. In addition, their proportions were compared between different genders in the 3 groups. RESULTS: The proportions of CD4+ T cells, naive CD4+ T cells and central memory CD4+ T cells were lower in AS patients (P = 0.001, P = 0.002 and P = 0.007, respectively) and RA patients (P = 0.032, P < 0.001 and P = 0.016, respectively), but the proportion of effector memory ones was higher when compared with healthy populations (both P < 0.001), as were the decrease of naive/central memory CD8+ T cells in AS (P = 0.003 and P = 0.016, respectively) and RA (P < 0.001 and P = 0.006, respectively), and the increased tendency of terminally differentiated CD8+ T cells. However, these above-mentioned cells, regulatory T (Treg) cells and CD8+ T cells with different CD127 expressions between AS and RA were similar in proportion. Furthermore, naive CD4+ T cells were positively associated with C-reactive protein (CRP) in AS, whereas CD4+ T cells and terminally differentiated CD8+ T of RA patients were associated with CRP in RA. The gender-related alterations predominantly displayed the overexpressions of Treg cells and naive CD8+ T cells in female patients with AS and RA, respectively. CONCLUSIONS: AS patients and RA patients have some similar peripheral CD4+ /CD8+ T cell subsets but are distinct from healthy individuals, which may contribute to disease severity. Females are respectively characterized by the up-regulation of Treg cells and naive CD8+ T cells in AS patients and RA patients. The study offers an in-depth understanding of the role of T cell subsets in the similarities of the disorders and helps us to monitor disease changes and may offer a theoretical basis of developing novel therapies against common targets.

Selection and Characterization of FD164, a High-Affinity Signal Regulatory Protein α Variant with Balanced Safety and Effectiveness, from a Targeted Epitope Mammalian Cell-Displayed Antibody Library.

Phagocytic resistance plays a key role in tumor-mediated immune escape, so phagocytosis immune checkpoints are a potential target for cancer immunotherapy. CD47 is one of the important phagocytosis immune checkpoints; thus, blocking the interaction between CD47 and signal regulatory protein α (SIRPα) may provide new options for cancer treatment. Using computer-aided targeted epitope mammalian cell-displayed antibody library, we screened and obtained an engineered SIRPα variant fragment crystallizable fusion protein, FD164, with higher CD47-binding activity than wild-type SIRPα Compared with wild-type SIRPα, FD164 has approximately 3-fold higher affinity for binding to CD47, which further enhanced its phagocytic effect in vitro and tumor suppressor activity in vivo. FD164 maintains the similar antitumor activity of the clinical research drug Hu5F9 in the mouse xenograft model. Furthermore, FD164 combined with rituximab can significantly improve the effect of single-agent therapy. On the other hand, compared with Hu5F9, FD164 does not cause hemagglutination, and its ability to bind to red blood cells or white blood cells is weaker at the same concentration. Finally, it was confirmed by computer structure prediction and alanine scanning experiments that the N45, E47, 52TEVYVK58, K60, 115EVTELTRE122, and E124 residues of CD47 are important for SIRPα or FD164 recognition. Briefly, we obtained a high-affinity SIRPα variant FD164 with balanced safety and effectiveness. SIGNIFICANCE STATEMENT: Up to now, few clinically marketed drugs targeting CD47 have been determined to be effective and safe. FD164, a potential signal regulatory protein α variant fragment crystallizable protein with balanced safety and effectiveness, could provide a reference for the development of antitumor drugs.

Identification of a novel protective human monoclonal antibody, LXY8, that targets the key neutralizing epitopes of staphylococcal enterotoxin B.

Staphylococcal enterotoxin B (SEB), one of the exotoxins produced by Staphylococcus aureus, is the key toxin that causes poisoning reactions and toxic shock syndrome. In the current research work, a novel human antibody named LXY8 was screened from a human phage display antibody library, and LXY8 blocked the interaction between SEB and the T cell receptor (TCR). The binding activity between LXY8 and SEB was 0.525 nM. Furthermore, LXY8 could effectively inhibit the SEB-induced activation of peripheral blood mononuclear cells and release of cytokines. In the BALB/c mouse model, LXY8 effectively neutralized SEB toxicity in vivo. Finally, based on computer-guided molecular modeling, we designed a series of SEB mutation sites; these sites facilitated the determination of the key residues (i.e.176EFNN179) of SEB recognized by LXY8. The research revealed that the 176EFNN179 residues of SEB are important for specific antibody-antigen recognition. The results may be helpful for the development of antibody-based therapy for SEB-induced toxic shock syndrome.