DOCK8 immunodeficiency syndrome (DIDS) is a combined immunodeficiency characterized by recurrent viral infections, severe atopy and early onset malignancy. Immunological abnormalities include lymphopenia, CD8+ T‐cell cytoskeleton dysfunction, defective B cell memory and variable serum immunoglobulin levels. Here, we analyse the B cell receptor repertoire (BCR) characteristics and antibody avidity of four DIDS patients, attempt to understand the dysregulated humoral immunity in DIDS patients with a normal antibody titre and suggest a scientific basis for intravenous immunoglobulin (IVIG) replacement therapy for these patients. We analysed BCR characteristics, including somatic hypermutation (SHM) frequency, using deep sequencing of multiplex PCR products derived from BCR heavy chain CDR3 regions from DIDS patients and controls. The antibody avidity of human tetanus and hemophilus influenza B antibodies was determined by ELISA using thiocyanate elution. IVIG replacement treatment and infection conditions were investigated retrospectively. We found skewing of the BCR repertoire and decreased antibody avidity in patients with DIDS. DIDS patients had fewer negatively charged amino acids than healthy controls. The SHM frequency of the IGHV3 gene was lower in patients with DIDS. Patients received regular IVIG therapy, resulting in fewer and less severe infections. We conclude that although IgG levels are normal in most DIDS patients, IVIG replacement therapy is still necessary. 相似文献
Systemic sclerosis (SSc) is an autoimmune disease mainly characterized by persistent inflammation and fibrosis. The receptor tyrosine kinase (RTK) signal pathway plays an important role in the process of SSc, and Grb2‐associated binding protein (GAB) is crucial in activating RTK signalling. A previous study found elevated levels of GAB1 in bleomycin (BLM)‐induced fibrotic lungs, but the effects of GAB1 in SSc remain unclear. Our aim was to investigate whether GAB1 was dysregulated and its potential role in SSc. Compared with healthy donors, we found GAB1 expression was 1.6‐fold higher in peripheral blood mononuclear cells (PBMC), 2.5‐fold higher in CD4 + T cells, and 2‐fold higher in skin from of SSc patients (P < .01). At the same time, the levels of type one collagen (COLI) were also significantly increased (1.8‐fold higher) in SSc skin. Additionally, BLM‐induced SSc mice showed mRNA levels of Gab1 2‐fold higher than saline‐treated controls, and Gab1 expression correlated positively with collagen content. A further in vitro study showed silencing of GAB1 suppressed inflammatory gene expression in TNF‐α induced fibroblasts. Additionally, GAB1 deficiency prominently inhibited cell proliferation and reduced COLI protein levels in TGF‐β induced fibroblasts. Taken together, these data suggest that GAB1 has a relatively high expression rate in SSc, and knockdown of GAB1 may attenuate SSc by stimulating inflammatory and fibrotic processes. 相似文献
This meta-analysis aimed to summarize the association between anthocyanin consumption and the risk of colorectal cancer.
All relative articles were located on online databases, including PubMed, Embase, and the Cochrane Library as of June 11, 2018. Risk ratios (RRs) or odds ratio and their 95% confidence intervals (CIs) were calculated through the STATA 12.0 software package.
A total of seven studies were included in the meta-analysis. A significant inverse association was found between total anthocyanin consumption and colorectal cancer risk (RR?=?0.78; 95% CI, 0.64–0.95). Likewise, there was significant evidence of a relationship between anthocyanin intake and colorectal cancer in the colon site (RR?=?0.81; 95% CI, 0.71–0.92); men (RR?=?0.88; 95% CI, 0.81–0.95), and case-control studies (RR?=?0.69; 95% CI, 0.60–0.78). A dose–response relationship was not found in this meta-analysis. The Grades of Recommendations Assessment, Development, and Evaluation quality in our study was very low.
This meta-analysis indicates that anthocyanin consumption is inversely associated with the risk of colorectal cancer. Anthocyanins may play an active role in the prevention of colorectal cancer.
Key teaching points:
Some epidemiological studies found an inverse correlation between the high consumption of anthocyanins and low risk of colorectal cancer.
Because of this structure, anthocyanins/anthocyanidins have a powerful capability of donating electrons, which can be characterized as antioxidant properties.
Anthocyanins can also inhibit colon cancer by interfering in the cell cycle and inducing the effect of anti-proliferation and apoptosis. The formation of cytoplasmic vacuoles in cells also indicates that anthocyanins may induce autophagy.
From the findings of nonrandomized controlled trials, anthocyanins may play an active role in the prevention of colorectal cancer.