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Decreased B1 and B2 Lymphocytes Are Associated With Mortality in Elderly Patients With Chronic Kidney Diseases.

ABSTRACT: Aim: Loss of renal function is associated with immune deficiency; however, few studies have addressed the role of B lymphocytes in elderly patients with chronic kidney disease (CKD). In this study, we examined the distribution and the relationship of the B lymphocyte subpopulation with clinical outcomes in elderly CKD patients. Methods: In this study, a total of 380 patients (312 CKD patients and 68 non-CKD controls) were recruited. Venous blood samples were analyzed by flow cytometry to determine the following B cell subsets: total B cells (CD19+), innate B1 cells (CD19+CD5+), and conventional B2 cells (CD19+CD5-). Correlations between the B cell subsets with clinical features and patient prognosis were analyzed. Results: A total of 380 patients (mean age 82.29 ± 6.22 years, 76.3% male) were included. The median follow-up time was 37.0 months (range, 1-109 months); 109 (28.7%) patients died. The main causes of death were infections (59.6%) and cardiovascular diseases (22.9%). Correlation analysis showed that levels of serum creatinine (SCr), blood urea nitrogen (BUN), and CKD were negatively associated with B1 cells. However, lymphocytes, T lymphocytes, and estimated glomerular filtration rate (eGFR) were positively correlated with B1 cells (all P < 0.05). B2 cells were negatively associated with age, SCr, cystatin C, BUN, and CKD, and were positively correlated with hemoglobin, lymphocytes, T lymphocytes, NK cells, and eGFR (all P < 0.05). Patient survival was significantly better in patients with B cells > 0.05 × 109/L, B1 cells > 0.02 × 109/L, and B2 cells > 0.04 × 109/L. Multivariate Cox regression analysis showed that B1 cells > 0.02 × 109/L [hazard ratio (HR) = 0.502, 95% confidence interval (CI): 0.297-0.851, P = 0.010] and B2 cells > 0.04 × 109/L (HR = 0.536, 95% CI: 0.319-0.901, P = 0.019) were independent protective factors for all-cause mortality. Conclusions: Our results showed that B1 and B2 cells exhibited a significantly negative correlation with the progression of CKD in elderly patients. Moreover, B1 and B2 cells were independent prognostic factors for survival, which indicates that the decrease in B cells may be associated with the progression of kidney diseases.

SUBMITTER: Lin J

PROVIDER: S-EPMC7098909 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Decreased B1 and B2 Lymphocytes Are Associated With Mortality in Elderly Patients With Chronic Kidney Diseases.

Lin Jieshan J Tang Wenfang W Liu Wei W Yu Feng F Wu Yanhua Y Fang Xiaowu X Zhou Maohua M Hao Wenke W Hu Wenxue W

Frontiers in medicine 20200320

<b>Aim:</b> Loss of renal function is associated with immune deficiency; however, few studies have addressed the role of B lymphocytes in elderly patients with chronic kidney disease (CKD). In this study, we examined the distribution and the relationship of the B lymphocyte subpopulation with clinical outcomes in elderly CKD patients. <b>Methods:</b> In this study, a total of 380 patients (312 CKD patients and 68 non-CKD controls) were recruited. Venous blood samples were analyzed by flow cytome ...[more]

PMID: 32266271

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Project description:Preeclampsia is a prevalent pregnancy complication characterized by new-onset maternal hypertension and inflammation, with placental ischemia as the initiating event. Studies of others have provided evidence for the importance of lymphocytes in placental ischemia-induced hypertension; however, the contributions of B1 versus B2 lymphocytes are unknown. We hypothesized that peritoneal B1 lymphocytes are important for placental ischemia-induced hypertension. As an initial test of this hypothesis, the effect of anti-CD20 depletion on both B-cell populations was determined in a reduced utero-placental perfusion pressure (RUPP) model of preeclampsia. Anti-murine CD20 monoclonal antibody (5 mg/kg, Clone 5D2) or corresponding mu IgG2a isotype control was administered intraperitoneally to timed pregnant Sprague-Dawley rats on gestation day (GD)10 and 13. RUPP or sham control surgeries were performed on GD14, and mean arterial pressure (MAP) was measured on GD19 from a carotid catheter. As anticipated, RUPP surgery increased MAP and heart rate and decreased mean fetal and placental weight. However, anti-CD20 treatment did not affect these responses. On GD19, B-cell populations were enumerated in the blood, peritoneal cavity, spleen, and placenta with flow cytometry. B1 and B2 cells were not significantly increased following RUPP. Anti-CD20 depleted B1 and B2 cells in peritoneum and circulation but depleted only B2 lymphocytes in spleen and placenta, with no effect on circulating or peritoneal IgM. Overall, these data do not exclude a role for antibodies produced by B cells before depletion but indicate the presence of B lymphocytes in the last trimester of pregnancy is not critical for placental ischemia-induced hypertension.NEW & NOTEWORTHY The adaptive and innate immune systems are implicated in hypertension, including the pregnancy-specific hypertensive condition preeclampsia. However, the mechanism of immune system dysfunction leading to pregnancy-induced hypertension is unresolved. In contrast to previous reports, this study reveals that the presence of classic B2 lymphocytes and peritoneal and circulating B1 lymphocytes is not required for development of hypertension following third trimester placental ischemia in a rat model of pregnancy-induced hypertension.

Project description:ObjectivesHigh-risk patients ≥65 y of age with coronavirus disease 2019 (COVID-19) tended to have lower serum prealbumin concentrations. The aim of this study was to investigate the association of prealbumin at baseline on COVID-19-related mortality in elderly patients (≥65 y of age).MethodsWe non-selectively and consecutively collected participants from Tongji Hospital in Wuhan from January 17 to February 17, 2020. Univariate and multivariate logistic regression models were employed to evaluate the correlation between prealbumin and in-hospital outcomes (in-hospital mortality, admission to the intensive care unit [ICU], and mechanical ventilation) in elderly patients with COVID-19. Linear trend was performed by entering the median value of each category of prealbumin tertile as a continuous variable and was visually confirmed by using generalized additive models. Interaction and stratified analyses were conducted as well.ResultsWe included 446 elderly patients with COVID-19 in the final analyses. In-hospital mortality was 14.79%. Of the 446 patients, 15.47% were admitted to the ICU and 21.3% required mechanical ventilation. Compared with patients in the highest tertile, the prealbumin of patients in the lowest tertile had a 19.09-fold higher risk for death [odds ratio (OR), 20.09; 95% confidence interval (CI), 3.62-111.64; P = 0.0006], 25.39-fold higher risk for ICU admission (OR, 26.39; 95% CI, 4.04-172.39; P = 0.0006), and 1.8-fold higher risk for mechanical ventilation (OR, 2.8; 95% CI, 1.15-6.78; P = 0.0227) after adjustment for potential confounders. There was a linear trend correlation between serum prealbumin concentration and risk for in-hospital mortality, ICU admission, and mechanical ventilation in elderly patients with COVID-19 infection.ConclusionPrealbumin is an independent risk factor of in-hospital mortality for elderly patients with COVID-19. Assessment of prealbumin may help identify high-risk individuals ≥65 y of age with COVID-19.

Project description:BackgroundChronic kidney disease (CKD) is age-related disease, and decreased renal function is associated with the premature aging of T cells and increased incidence of other age-related diseases. However, the relationship between T cell senescence and CKD progression remains unclear. Here, we investigated the relationship between T cell senescence, as indicated by decreased thymic output and increased proportion of highly differentiated CD28- T cells, and CKD progression.ResultsA total of 175 patients with non-dialysis-dependent CKD were enrolled in this study. Thymic output was assessed based on the CD45RA+CD31+CD4+ cell (recent thymic emigrant [RTE]) counts (RTEs) (/mm3) and the proportion of RTE among CD4+ T cells (RTE%). Highly differentiated T cells were assessed based on the proportion of CD28- cells among CD4+ T cells (CD28-/CD4+) and CD28- cells among CD8+ T cells (CD28-/CD8+). The primary outcome was estimated glomerular filtration rate (eGFR) decline of ≥40% or initiation of renal replacement therapy. The association between T cell senescence and renal outcomes was examined using Cox proportional hazards models and restricted cubic splines. The median age was 73 years, 33% were women, and the median eGFR was 26 mL/min/1.73 m2. The median RTEs, RTE%, CD28-/CD4+, and CD28-/CD8+ were 97.5/mm3, 16.2, 5.3, and 49.7%, respectively. After a median follow-up of 1.78 years, renal outcomes were observed in 71 patients. After adjusting for age, sex, eGFR, proteinuria, diabetes, and cytomegalovirus seropositivity, decreased RTEs, which corresponded to decreased thymic output, significantly and monotonically increased the risk of poor renal outcome (p = 0.04), and decreased RTE% and increased highly differentiated CD28-/CD4+ T cells also tended to monotonically increase the risk (p = 0.074 and p = 0.056, respectively), but not CD28-/CD8+ T cells.ConclusionsDecreased thymic output in CKD patients, as well as increased highly differentiated CD4+ T cells, predicted renal outcomes. Thus, the identification of patients prone to CKD progression using T cell senescence, particularly decreased RTE as a biomarker, may help to prevent progression to end-stage kidney disease.

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Decreased B1 and B2 Lymphocytes Are Associated With Mortality in Elderly Patients With Chronic Kidney Diseases.

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Decreased B1 and B2 Lymphocytes Are Associated With Mortality in Elderly Patients With Chronic Kidney Diseases.

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