Allergen-specific immunotherapy is widely used for allergic rhinitis and asthma treatment worldwide. This study explored the efficacy and safety of sublingual immunotherapy (SLIT) with the extracts of Dermatophagoides Farinae (D. farinae Drops) on house dust mites (HDM)-induced atopic dermatitis (AD). 239 patients with HDM-induced AD were recruited and exposure to a multi-centre, randomized, double-blind, and placebo-controlled clinical trials for 36 weeks, which were randomly divided into placebo and sublingual D. farinae Drops groups (high-dose, medium-dose and low-dose), respectively. Statistical analysis was performed in three groups: Full Analysis Set, Per Protocol Set and Safety Set. 48 cases have withdrawn from the study before the end of study. As primary outcomes, significant decreases in scoring atopic dermatitis and total medication score were showed in medium-dose and high-dose D. farinae Drops groups. In the sixth visit, the skin lesion area showed a statistically significant difference between high-dose/medium-dose D. farinae Drops group and placebo group (p < .05). Most adverse events are slight, and no life-threatening adverse drug reaction happened. Our research demonstrates the beneficial effect of SLIT with high or medium dose D. farinae Drops on AD, and the treatment was well tolerated.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with complicated genetic inheritance. Programmed death 1 (PD-1), a negative T cell regulator to maintain peripheral tolerance, induces negative signals to T cells during interaction with its ligands and is therefore a candidate gene in the development of SLE. In order to examine whether expression levels of PD-1 contribute to the pathogenesis of SLE, 30 patients with SLE and 30 controls were recruited and their PD-1 expression levels in peripheral blood mononuclear cells (PBMCs) were measured via flow cytometry and quantitative real-time-reverse transcription polymerase chain reaction (RT-PCR). Also, whether PD-1 expression levels are associated with the variant of the SNP rs36084323 and the SLE Disease Activity Index (SLEDAI) was studied in this work. The PD-1 expression levels of SLE patients were significantly increased compared with those of the healthy controls. The upregulated PD-1 expression levels in SLE patients were greatly associated with SLEDAI scores. No significant difference was found between PD-1 expression levels and SNP rs36084323. The results suggest that increased expression of PD-1 may correlate with the pathogenesis of SLE, upregulated PD-1 expression may be a biomarker for SLE diagnosis, and PD-1 inhibitor may be useful to SLE treatment.

Systemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disease. The T cell immunoglobulin and mucin domain (TIM) family is associated with autoimmune diseases, but its level of expression in the immune cells of patients with SLE is still uncertain. The aim of this study was to examine whether TIM-3 and Galectin-9 (Gal-9) contribute to the pathogenesis of SLE. In total, 30 patients with SLE and 30 healthy controls were recruited, and their levels of TIM-3 expression in peripheral blood mononuclear cells (PBMCs) were examined via flow cytometry. Meanwhile, the levels of Gal-9 expression in serum and in PBMCs were measured via an enzyme-linked immunosorbent assay (ELISA) kit and immunofluorescence staining, respectively. The relation between the level of TIM-3 or Gal-9 expression and the SLE disease activity index (SLEDAI) was also studied. Finally, the function of the TIM-3 and Gal-9 pathway in the pathogenesis of SLE was explored. Our results showed that the levels of expression of TIM-3 and Gal-9 on CD4(+) T cells, CD8(+) T cells, CD56(+) T cells and in serum in patients with SLE were significantly higher than those of healthy controls. We found that the level of Gal-9 expression was significantly higher in both serum and PMBCs of patients with SLE than in healthy controls. The up-regulation of TIM-3 and Gal-9 expression in patients with SLE was closely related to the SLEDAI scores. In addition, Gal-9 blocking antibody significantly inhibited CD3-stimulated PBMC proliferation and Th1-derived cytokines (IL-2, IFN-γ, and TNF-α), Th2-derived cytokines (IL-4, IL-10), a Th17-derived cytokine (IL-17A), and release of a pro-inflammatory factor (IL-6) in patients with SLE. The results suggest that increased expression of TIM-3 and Gal-9 may be a biomarker for SLE diagnosis and that the TIM-3 pathway may be a target for SLE treatment.

Blockade of the interactions between C028/CTLA-4 and their ligands, C080 (B7, B7.1)/C086 (B70, B7.2), is an attractive means to induce antigen-specific peripheral tolerance in autoimmune disease and organ transplantation. In this study, we generated and characterized a monoclonal antibody (Clone 4E5) against human C080. 4E5 could recognize both human and mouse C080 and suppress mixed lymphocyte reaction in vitro. To investigate their potency for clinical use, we further administrated 4E5 to a mouse lupus-like disease model (C57BL/J6) induced by Pristane. 4E5 could inhibit the immune response and attenuate the severity of lupus-like disease. The data showed 4E5 function and suggested that blockade of C080/C028 co-stimulatory signal pathway with 4E5 is a promising strategy to decelerate the progression of lupus-like disease and other autoimmune diseases.

Summary Background Atopic dermatitis (AD) is a heterogeneous disease, characterized by excess T helper (Th) 22 activation in Asian AD. Inducible T‐cell costimulator (ICOS) is crucial for T‐cell activation and differentiation. However, the role of ICOS in AD and its effect on Th22 cells remain unclear. Objectives To gain a better understanding of the role of ICOS and ICOS ligand (ICOSL) in the pathogenesis of Asian AD and its underlying mechanisms. Methods We quantified ICOS and ICOSL expression in Han Chinese patients with AD and healthy controls (HC). Then, we assessed the proliferation and the production of the Th22 chemokines CCR4 and CCR10 by ICOSL‐stimulated AD peripheral blood mononuclear cells (PBMCs) as well as their effects on keratinocyte filaggrin production. Finally, we explored the link between ICOS‐expressing Th22 cells and disease activity and IgE levels in our patients with AD. Results Our patients with AD showed higher levels of ICOS‐expressing Th22 cells as well as ICOSL‐expressing CD19+ B cells and CD14+ monocytes compared with HC. ICOSL increased the proliferation and expression of CCR4 and CCR10, and of interleukin (IL)‐22 in AD PBMCs. ICOSL treatment also significantly increased the downregulation of filaggrin expression by keratinocytes cocultured with PBMCs from patients with AD. Finally, blood levels of ICOS+ Th22 cells and ICOSL+ B cells in this AD cohort were correlated with disease activity as assessed by the SCORing Atopic Dermatitis index and with total IgE levels. In Han Chinese patients with AD, circulating Th22 cells, serum levels of IL‐22 and IL‐22+ cells in lesional skin were all markedly increased. Conclusions Our findings demonstrate that ICOS/ICOSL expression and effects are linked to Th22 skewing and the pathogenesis of Han Chinese AD, which suggests ICOSL and ICOS as well as Th22 cells and IL‐22 as new and promising therapeutic targets. What's already known about this topic? In Asian patients, atopic dermatitis (AD) is characterized by excess T helper (Th) 22 activation. Inducible T‐cell costimulator (ICOS) is crucial for T‐cell activation and differentiation. What does this study add? This study demonstrates that circulating Th22 cells, serum levels of interleukin (IL)‐22 and IL‐22+ cells are all markedly increased in lesional skin in Han Chinese patients with AD. In Han Chinese patients with AD, ICOS and ICOS ligand (ICOSL) drive Th22 skewing and increase filaggrin downregulation, and ICOS+ Th22 cells and ICOSL+ B cells are linked to disease activity. What is the translational message? ICOS+ Th22 cells and ICOSL+ B cells are potential clinical biomarkers of disease activity in Han Chinese patients with AD. ICOS‐ and ICOSL‐targeted treatment approaches may benefit Han Chinese patients with AD.