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Background and aims: Although type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) share many common pathological and physiological characteristics, there are few studies assessing the predictive capacity of novel biomarkers in occurrence and development of CAD in T2DM patients aged ≥ 65 years. In addition, T2DM patients aged ≥ 65 years are prone to CAD. Therefore, it is of great significance to find novel biomarkers for the development in T2DM to CAD. Methods 579 T2DM patients aged ≥ 65 years were consecutively enrolled in this work, and 177 of whom had major adverse cardiovascular and cerebrovascular events (MACCE: cardiovascular or cerebrovascular death, acute coronary syndrome, coronary stent implantation, and stroke) during the follow up. Univariate and multivariate factors were employed to analyze the correlation between each variable and the occurrence of MACCE, and the Spearman’s rank correlation analysis was performed to assess the relationships between Neutrophil gelatinase-associated lipocalin (NGAL) and sdLDL-C and other characteristics. The receiver operating characteristic (ROC) curve was adopted to determine the predictive value of NGAL and sdLDL‐C elevation for MACCE in T2DM patients aged ≥ 65 years. Results After a median 4-year follow-up (interquartile range (IQR) = 2.7 years), the levels of NGAL, sdLDL-C, hemoglobin A1c (HbA1c), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (ApoB) were significantly higher while those of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A I (ApoA‐I) were lower in MACCE positive group. NGAL correlated to body mass index (BMI) (r = 0.391, P = 0.001) and triglyceride (TG) (r = 0.228, P = 0.032), and high-sensitivity CRP (hsCRP) (r = 0.251, P = 0.007), and neutrophils (r = 0.454, P = 0.001) closely. sdlDL‐C level was found to be positively correlated with LDL-C (r = 0.413, P = 0.001), TG (r = 0.432, P = 0.001), and ApoB (r = 0.232, P = 0.002); and it was negatively correlated with HDL-C (r = -0.362, P = 0.031) and ApoA‐I (r = -0.402, P = 0.001). Age-adjusted Cox regression analysis showed that NGAL (HR = 1.008, 95% confidence interval (CI): 1.006–1.009, P < 0.001) and sdLDL‐C (HR = 1.059, 95% CI: 1.046–1.072, P < 0.001) were independently associated with occurrence of MACCE. ROC curve analysis showed that NGAL and sdlDL‐C could strongly predict the occurrence of MACCE (area under ROC (AUC) = 0.79, 95% CI: 0.75–0.84, P < 0.001) (AUC = 0.76, 95% CI: 0.72–0.80, P < 0.001). Combined NGAL with sdlDL‐C could predict the occurrence of MACCE well (AUC = 0.87, 95% CI: 0.84–0.90, P < 0.001). Conclusions The higher NGAL and sdLDL-C in T2DM patients aged ≥ 65 years were significantly and independently associated with the risk of MACCE. Serum NGAL and sdLDL‐C showed higher clinical values than other lipid biomarkers or other chronic inflammation which were expected to be the most effective predictors of MACCE assessment.

Background: Allergic rhinitis (AR) is characterized by type Ⅰ hypersensitivity that is mediated by IgE-induced humoral responses. It is known that follicular helper T cells (Tfh) comprise the key Th cell subset that promotes antibody production. Signaling lymphocytic activation molecule (SLAM) participates in the regulation of the differentiation and function of Tfh cells, but whether this regulation is involved in the pathogenesis of AR is unknown.Methods: CD4+CXCR5+ Tfh-like cells from peripheral blood were detected by flow cytometry. The levels of IL-21 and IgE in serum were tested by ELISA. Blood CD4+CXCR5+ Tfh-like cells were sorted and cultured with anti-SLAM mAb in vitro.Results: The frequencies of circulating CD4+CXCR5+ Tfh-like cells appeared virtually unchanged in AR patients, but the expression of SLAM and SLAM-associated protein (SAP) on circulating Tfh-like cells was significantly decreased. Meanwhile, the level of serum IL-21 was increased in AR patients, and there was a negative correlation between the levels of IL-21 and the expression of SLAM or SAP in CD4+CXCR5+ T cells. Treatment with anti-SLAM mAb resulted in the reduced production of IL-21 by Tfh-like cells in vitro. Additionally, the expression of SLAM on B cells significantly decreased, although the percentages of B cells were increased in AR patients.Conclusions: SLAM negatively regulates the production of IL-21 in CD4+CXCR5+ Tfh-like cells, which contributes to the pathogenesis of AR.

Autoantibodies produced by B cells play a pivotal role in the pathogenesis of systemic lupus erythematosus (SLE). However, both the cellular source of anti-phospholipid antibodies and their contributions to the development of lupus nephritis (LN) remain largely unclear. Here, we report a pathogenic role ofanti-phosphatidylserine (PS) autoantibodies in the development of LN. In cohort study and mouse models, elevated serum PS-specific IgG levels were detected in SLE patients, especially in those with nephritis, and lupus mice. The deposition of PS-specific IgG was detected in kidney biopsied of lupus nephritis patients. Both transfer of SLE PS-specific IgG and PS immunization triggered lupus-like glomerular immune complex deposition in recipient mice. ELISPOT analysis identified B1a cells as the main cell type for secreting PS-specific IgG in both lupus mice and patients. Adoptive transfer of PS-specific B1a cells accelerated PS-specific autoimmune response and renal damage in recipient lupus mice whereas depletion of B1a cells attenuated lupus progression. In culture, PS-specific B1a cells were significantly expanded upon treatment with chromatin components while blockade of TLR signal cascades by DNase I digestion, inhibitory ODN 2088 or R406 treatment profoundly abrogated chromatin-induced PS-specific IgG secretion by lupus B1a cells. Thus, our study has demonstrated that the novel anti-PS autoantibodies produced by B1 cells contribute to lupus nephritis development. Our findings that blockade of TLR/Syk signaling cascade inhibits PS-specific B1 cell expansion may provide new insight in understanding lupus pathogenesis and may help develop novel therapeutic targets for the treatment of LN in SLE.

Background Primary Sjögren’s syndrome (pSS) is a chronic systemic autoimmune disease characterized by lymphocytic infiltrates in exocrine glands. Mesenchymal stem cells (MSCs) have been proved to be effective in the treatment of different autoimmune diseases. Although MSC transplantation has been demonstrated to be an effective therapeutic approach to treat SS, the underlying mechanisms are still elusive. Our previous study has identified the reduced suppressive capacity of MDSCs advanced the progression of experimental Sjögren’s syndrome (ESS). Methods The ESS mouse model was induced with murine salivary glands proteins emulsified in an equal volume of Freund’s adjuvant. Both frequency and phenotype of MDSCs during ESS development in mice were analyzed by flow cytometry. The suppressive capacity of MDSCs was examined by CD4+ T cell proliferation test, CFSE-labelled CD4+ T cell was analyzed by flow cytometry. Both phenotype and function of MDSCs upon MSCs treatment were analyzed in vitro and in vivo. The function of MSCs in modulating the suppressive function of MDSCs was further evaluated by silencing TGF-β in MSCs. Results In this study, we found that BM-MSCs significantly enhanced the suppressive function of MDSCs (PMN-MDSCs/M-MDSCs) with high levels of Arginase and NO, decreased the levels of CD40, CD80, CD86 and MHC-II expression on MDSCs, thus attenuating the disease progression in ESS mice. Furthermore, the enhanced suppressive function of MDSCs was mediated by BM-MSC-secreted TGF-β, and the therapeutic effect of BM-MSCs in inhibiting ESS was almost abolished after silencing TGF-β in BM-MSCs. Conclusions Taken together, our results demonstrated that BM-MSCs alleviated the ESS progression by up-regulating the immunosuppressive effect of MDSCs through TGF-β/Smad pathway, offering a novel mechanism for MSCs in the treatment of pSS.