The diagnostic role of PD-1+ CXCR5+ follicular helper CD8+ T cell in renal allograft dysfunction.

BACKGROUND: The roles of PD-1+ CXCR5+ follicular helper CD8+ T cell were reported in different disease conditions, but their roles in transplantation are unclear. In this study, the association between PD-1+ CXCR5+ follicular helper CD8+ T cell and renal allograft dysfunction in kidney transplant recipients (KTRs) was investigated. METHODS: 82 KTRs were enrolled in this study. 45 KTRs were included in the chronic allograft dysfunction (CAD) group, and 37 KTRs were included in the stable recipients group. Among the CAD group, 12 cases of antibody-mediated rejection (ABMR) and 4 cases of T cell-mediated rejection (TCMR) were diagnosed by biopsy. The percentage of CXCR5+ CD8+ T cells and the co-expression of signal transducers and activators of transcription 4 (STAT4), STAT5, and PD-1 in peripheral blood were determined by flow cytometry. RESULTS: The expression of CXCR5 on CD3+ CD8+ T cells and the percentage of STAT5+ CXCR5+ cells in the CD3+ CD8+ T-cell population were significantly lower in the CAD group (p < 0.05), while the expression of PD-1+ CXCR5+ CD8+ T cells was significantly higher (p < 0.05). Through logistic regression analysis, we concluded that the percentage of PD-1+ CXCR5+ CD8+ T cells was an independent risk factor for renal dysfunction. Grouping by pathological type, PD-1+ CXCR5+ CD8+ T cells showed relatively good diagnostic efficacy for ABMR by ROC analysis. CONCLUSIONS: Our results suggested that PD-1+ CXCR5+ CD8+ T cells were a promising biomarker for distinguishing renal allograft dysfunction and different allograft pathological types. Also, our findings may provide new ways of identifying and treating allograft rejection.

Alimentary system is directly attacked by SARS-COV-2 and further prevents immune dysregulation caused by COVID-19.

BACKGROUND: SARS-COV-2 causes digestive system symptom, the effect of which remains equivocal. METHODS: Patients with COVID-19 were classified into four groups according to symptom. The study traced the onset and duration of symptoms, compared laboratory examinations and conducted bioinformatic analysis. Immune indices were further analysed. RESULTS: By March 16, 25 patients with COVID-19 and 13 with suspect COVID-19 were admitted to West China Hospital, Sichuan University. Digestive system symptom group had the highest level of ESR (mm/h, P < .0001), serum ferritin (ng/ml, P < .0001), hepatic enzymes (P < .05) and retentive lymphocyte count/percentage (P < .05) and its subsets (P < .05). Combined group (respiratory combined with subsequent digestive system symptom) had the highest level of IL-6 (pg/ml, P = .0046), CRP (mg/L, P = .0004) and moderate lymphocyte depletion. Respiratory system symptom and asymptomatic groups suffered the most from lymphocyte depletion (P < .05). Bioinformatic analysis indicated co-expression of binding related proteins of SARS-COV-2 (ACE2, TMPRSS2 and Furin) in small intestine. CD147 was extensively expressed in alimentary tract. CTSL, PIKfyve, TPC2 and CTSB could be detected with ≥moderate expressions in a variety of organs including alimentary system. CONCLUSIONS: Alimentary system is possibly attacked by SARS-COV-2 other than hyperinflammation or immune dysregulation caused by it. Involvement of alimentary system might further protect mild and moderate cases from lymphocyte depletion caused by COVID-19.

Clinical Significance of Serum IgG4 in the Diagnosis and Treatment Response of IgG4-Related Disease in Adults of Southwest China: A Retrospective Study.

Background: There is no standard cut-off value of serum IgG4 concentration and serum IgG4/total IgG ratio for the diagnosis of IgG4-related disease (IgG4-RD) or as a marker of treatment responses. We aimed to explore this issue through a retrospective cohort analysis of adults in southwest China. Methods: The diagnostic performance of serum IgG4 concentration and IgG4/IgG ratio for IgG4-RD was evaluated in a retrospective analysis of 177 adults newly diagnosed as having IgG4-RD and 877 adults without IgG4-RD. Dynamic analysis was performed to evaluate the significance of serum IgG4 concentration on IgG4-RD treatment responses. Results: The serum IgG4 concentration differed according to sex. The optimal cut-off values of serum IgG4 concentration and IgG4/IgG ratio for IgG4-RD diagnosis were 1.92 g/L and 0.12 in males and 1.83 g/L and 0.11 in females, respectively. For patients with serum IgG4 concentration >2.01 g/L, the cut-off values in the total population were >3.00 g/L and 0.19, respectively. The median serum IgG4 concentration decreased over time, and the decrease rate increased over time. The serum IgG4 concentration significantly decreased at >1 week post-treatment (P=0.004), and the median decrease rate was close to 50% at >4 weeks post-treatment. Conclusions: Serum IgG4 can be a good indicator for IgG4-RD diagnosis; however, different diagnostic cut-off values should be determined according to sex. The decreasing rate is more conducive than the serum IgG4 concentration to monitor treatment efficacy. The IgG4/IgG ratio did not improve the diagnostic efficacy for IgG4-RD.

Homogeneous Dual Fluorescence Count of CD4 in Clinical HIV-Positive Samples via Parallel Catalytic Hairpin Assembly and Multiple Recognitions.

Regularly measuring the level of CD4+ cells is necessary for monitoring progression and predicting prognosis in patients suffering from an infection with the human immunodeficiency virus (HIV). However, the current flow cytometry standard detection method is expensive and complicated. A parallel catalytic hairpin assembly (CHA)-assisted fluorescent aptasensor is reported for homogeneous CD4 count by targeting the CD4 protein expressed on the membrane of CD4+ cells. Detection was achieved using CdTe quantum dots (QDs) and methylene blue (MB) as signal reporters. CdTe QDs distinguished CHA-assisted release of Ag+ and C-Ag+-C and MB that has differentiated cytosine (C)-rich single-stranded DNA (ssDNA) and C-Ag+-C, generating changes in fluorescence intensity. With the assistance of the CHA strategy and luminescent nanomaterials, this method reached limits of detection of 0.03 fg/mL for the CD4 protein and 0.3 cells/mL for CD4+ cells with linear ranges of 0.1 to 100 fg/mL and 1 to 1000 cells/mL, respectively. The method was validated in 50 clinical whole blood samples consisting of 30 HIV-positive patients, 10 healthy volunteers, and 10 patients with cancer or other chronic infections. The findings from this method were in good agreement with the data from clinical flow cytometry. Due to its sensitivity, affordability, and ease of operation, the current method has demonstrated great potential for routine CD4 counts for the management of HIV, especially in communities and remote areas.