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Background. Genomic testing gives guidance to the treatment options in lung adenocarcinoma patients, but some patients are unable to obtain tissue samples due to lesion location or intolerance. Cell-free circulating tumor DNA (ctDNA) tested in plasma or pleural effusion is an advanced access to solve the problem. Our study descriptively identified the genetic variations of advanced Chinese lung adenocarcinoma patients and analyzed the overall survival of patients with EGFR mutations. Methods. A total of 152 patients' plasma samples were included, and gene mutations were detected by NGS using an Illumina Miseq tabletop sequencer. Results. Frequencies of altered were EGFR 46.05%, ALK 7.24%, KRAS 6.58%, PIK3CA 6.58%, PTEN 2.63%, HER2 1.97%, MET 1.97%, BRAF 1.32%, NF1 1.32%, and ROS1 0.66%. We identified 48 cases with double or triple driver gene mutations. Multiple mutations were more frequently observed in EGFR and PIK3CA genes. Patients harboring coexistent mutations with an EGFR mutation tended to have a shorter overall survival than those with exclusively EGFR mutations. Conclusion. EGFR, ALK, and KRAS were common driver gene in Chinese patients with stage IV lung adenocarcinoma. Multiple mutations were detected in the ctDNA samples and involve more EGFR and PIK3CA mutations. The existence of coexisting gene mutations may have adverse effects on the prognosis of patients with EGFR mutation. The unknown mutations discovered by NGS may provide new targets for gene targeting therapy, and ctDNA test by NGS is an effective method for making appropriate treatment choices. [ABSTRACT FROM AUTHOR]

There are significant differences in pathology, etiology, clinical features, and treatment options between small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). However, the differences of macrophage distribution and its associated function between SCLC and NSCLC are not fully investigated. Through methods of flow cytometry and cytometric bead array, we examined the levels of various subtypes of macrophages, monocytes, and regulatory T cells (Tregs) as well as interleukin (IL)-10 in bronchoalveolar lavage fluid (BALF) of patients with SCLC or NSCLC. Our study showed that the frequency of CD14+, CD206+CD14+ and IL-10+CD206+CD14+M2-like macrophages were significantly increased, with simultaneously elevated IL-10 in BALF of SCLC patients, as compared to those in BALF of NSCLC patients. Furthermore, the increased frequency of IL-10+CD206+CD14+M2-like macrophages and elevated level of IL-10 in BALF of SCLC patients were positively correlated with advanced tumor stage, but negatively correlated with their survival time. On the other hand, the level of supernatant IL-10 and frequency of IL-10+CD206+CD14+M2-like macrophages in SCLC patients were positively correlated. The frequency of above mentioned macrophages was also positively correlated with that of Foxp3+CD25+CD4+Tregs. Compared to NSCLC patients, the level of circulating IL-10+CD206+CD14+M2-like monocytes in SCLC patients were significantly increased after chemotherapy. Overall, increased IL-10+CD206+CD14+M2-like macrophages were an important feature of SCLC, rather than NSCLC, and it is associated with development of SCLC. [ABSTRACT FROM AUTHOR]

The present study was designed to evaluate the percentage of different programmed cell death‐1 (PD‐1)+ T cell subsets in peripheral blood and bronchoalveolar lavage fluid (BALF) of small cell lung cancer (SCLC) patients. The percentages of PD‐1+ T cell subsets in peripheral blood and BALF samples obtained from 52 lung cancer and 20 pneumonia patients, and 20 healthy controls were examined by flow cytometry. In addition, clinical parameters, such as erythrocyte sedimentation rate (ESR) and C‐reactive protein (CRP) levels, were also determined using Spearman's correlation test to assess their association with PD‐1+ T cell subsets. These present results revealed that the percentage of circulating PD‐1+ Tfh and peripheral helper T cells (Tph) cells significantly increased in peripheral blood of SCLC patients, when compared to non‐small cell lung cancer (NSCLC) pneumonia patients and healthy controls. In addition, PD‐1+ Tfh cells were also significantly enhanced in patients in the extensive‐stage group. In contrast, the BALF samples of SCLC patients exhibited a significant decrease in percentage of Tph cells. An overall imbalance was observed between PD‐1+Tfh and Tph cells in both compartments. Furthermore, SCLC patients exhibited a significant decrease in the percentage of circulating PD‐1+ Tfh and Tph cells following chemotherapy, and the in vitro analysis revealed that the concentration of IL‐2 and IFN‐γ derived from PD‐1 + Tfh cells in SCLC were significantly lower than that from NSCLC. However, this had no significant correlation with disease severity. The present study indicated that elevated circulating PD‐1+ T cells can primarily be used as a biomarker for disease diagnosis and a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Background: T follicular helper (Tfh) cells are known to regulate humoral immune response. In this study we examined the correlation of different subsets of peripheral blood Tfh cells in patients with diabetic nephropathy (DN).Methods: A total of 23 DN patients and 15 healthy controls (HC) were investigated for various subsets of Tfh cells by flow cytometry. The molecules ICOS+, PD-1+, CD28+, CD154+, IL-21+, IFN-γ+, IL-4+, IL-17+Tfh cells were examined. The subsets of B cells were investigated by flow cytometry. The levels of 24 h urinary protein and estimated glomerular filtration rate (eGFR) were calculated. A potential correlation between the number of different subsets of Tfh cells, B cells and DN, was assessed.Results: The circulating CD4+CXCR5+PD-1+, PD-1+CD154+, PD-1+CD28+, PD-1+IL-21+, PD-1+IL-4+, PD-1+-IL-17+-Tfh cell counts, CD38+CD19+, CD38+CD19+CD40+B cells and plasma levels of IL-21 were significantly increased in DN patients (p < 0.05), as compared to that in the HC group. Furthermore, the circulating CD4+CXCR5+PD-1+Tfh cell counts negatively correlated with eGFR; Tfh cell counts positively correlated with 24 h urinary protein concentration in DN patients. Post-treatment, there was a significant reduction in the CD4+CXCR5+PD-1+Tfh cell counts and its subsets, with a corresponding decrease in plasma levels of IL-6 and IL-17A (p < 0.05) in DN patients, as compared to the HCs.Conclusion: An increased number of CD4+CXCR5+PD-1+Tfh cells were observed in DN patients, which may be new targets for intervention in DN. [ABSTRACT FROM AUTHOR]

Background: Henoch—Schoenlein purpura is the one of most common types of systemic vasculitis that involves impaired renal function and Henoch-Schoenlein purpura nephritis (HSPN). The diagnosis of this condition is largely based on immunohistologic detection of immunoglobulin A1-containing immune complex in the glomerular deposits of mesangium. Despite clinical advances, the etiopathogenesis of HSPN is still largely unknown. Methods: In this study, we enrolled 25 newly diagnosed HSPN patients and 14 healthy controls. Then, fractions of B cell subtypes were determined in venous blood using flow cytometry. The serum interleukin (IL)-10 concentration was determined by enzyme-linked immunosorbent assay. Results: Compared to those in healthy controls, the numbers of CD38+CD19+, CD86+CD19+, CD38+CD86+CD19+, and CD95+CD19+ B cells per microliter of blood were significantly higher in HSPN patients. In contrast, the numbers of CD5+CD19+, IL-10+CD19+, CD5+CD1d+CD19+, and IL-10+CD5+CD1d+CD19+ B cells per microliter of blood and the serum IL-10 concentration were significantly lower in HSPN patients. Following treatment, the numbers of CD38+CD19+ and CD86+CD19+ B cells per microliter of blood were significantly reduced in HSPN patients. However, the numbers of CD5+CD1d+CD19+, CD5+CD1d+IL-10+CD19+, and IL-10+CD19+ B cells per microliter of blood and the serum IL-10 concentration were significantly increased in HSPN patients following treatment. The estimated glomerular filtration rate (eGFR) was negatively correlated with the number of CD38+CD19+ B cells but positively correlated with the numbers of IL-10+CD19+, CD1d+CD5+CD19+, and IL-10+CD1d+CD5+CD19+B cells per microliter of blood and the serum IL-10 concentration. The 24-h urinary protein concentration was positively correlated with the number of CD38+CD19+B cells but negatively correlated with the numbers of IL-10+CD19+, CD1d+CD5+CD19+, and IL-10+CD1d+CD5+CD19+B cells per microliter of blood and the serum IL-10 concentration. Conclusion: Our results suggest that CD38+CD19+ and CD1d+CD5+CD19+ B cells (Bregs) contribute to the pathogenesis of HSPN. [ABSTRACT FROM AUTHOR]

Objective: This study is aimed at examining the potential roles of circulating memory T follicular helper (Tfh) cells in patients with multiple sclerosis (MS). Methods: The numbers of different subsets of circulating memory Tfh cells in 25 patients with relapsed MS before and after treatment as well as 14 healthy controls (HC) were examined by flow cytometry. The levels of plasma IL-21 in all patients and cerebrospinal fluid (CSF) IL-21 in some MS patients and controls with non-inflammatory neuronal diseases (NND) were measured by ELISA. Results: In comparison with that in the HC, the numbers of circulating CD3+CD4+CXCR5+CD45RA-, ICOS+, CCR7+ and CCR7+ICOS+ memory Tfh cells and the levels of plasma IL-21 significantly increased in MS patients, but significantly decreased in the patients with complete remission (CR). The levels of CSF IL-21 were significantly higher in the MS patients than that in the NND patients. The numbers of CCR7+ICOS+ memory Tfh cells were positively correlated with the EDSS scores, the levels of plasma and CSF IL-21, IgG, MBP-Ab or MOG-Ab. Conclusions: Our findings indicated that circulating memory Tfh cells, especially CCR7+ICOS+ memory Tfh cells, may be associated with the relapse of MS and may serve as a new therapeutic target. [ABSTRACT FROM AUTHOR]