Analysis of peripheral blood lymphocyte subsets in critical patients at ICU admission: A preliminary investigation of their role in the prediction of sepsis during ICU stay.
Frattari Antonella,Polilli Ennio,Primiterra Vanessa,Savini Vincenzo,Ursini Tamara,Di Iorio Giancarlo,Parruti Giustino
International journal of immunopathology and pharmacology
A better knowledge of factors predicting the development of sepsis in patients hospitalized in intensive care unit (ICU) might help deploy more targeted preventive and therapeutic strategies. In addition to the known clinical and demographic predictors of septic syndromes, in this study, we investigated whether measuring T and B lymphocyte subsets upon admission in the ICU may help individualize the prediction of ensuing sepsis during ICU stay. Between May 2015 and December 2016, we performed a prospective cohort study evaluating peripheral blood lymphocyte T-CD4+ (T-helper cells), T-CD8+ (cytotoxic T-cells), T-CD56 + (natural killer cells), and T-CD19+ (B-lymphocytes), using flow cytometry on blood samples collected 2 days after admission in the ICU. We enrolled 176 patients, 65.3% males, with mean age of 61.1 ± 15.4 years. At univariate analyses, higher percentages of CD19 B-cells were significantly associated with ensuing sepsis (20.5% (15.7-27.7)% vs 16.9% (11.3-22)%, P = 0.0001), whereas median interquartile range (IQR) proportions of CD4 T-cells (41.2% (33.4-50.6)% vs 40% (35-47)%, P = 0.5), CD8 T-cells (21.1% (15.8-28.2)% vs 19.6% (14.6-25.1)%, P = 0.2) and CD56 T-cells (1.7% (0.9-3.1)% vs 1.45% (0.7-2.3)%, P = 0.4) did not reveal any significant association. An unexpected, highly significant inverse correlation of CD8 T-cells and CD19 B-cells proportions, however, was observed, suggesting that patients with lower CD19 and higher CD8 proportions might be somehow protected from ensuing sepsis. We therefore studied the ability of the CD8/CD19 ratio to predict ensuing sepsis in our sample. In final models of multivariate logistic regression, the following independent associations were found: previous antibiotic exposure (odds ratio (OR): 3.8 (95% confidence interval (CI): 1.35-10.87), P = 0.01), isolation of at least one multi-drug resistant organism at any time during ICU stay (OR: 8.4 (95% CI: 3.47-20.6), P < 0.0001), decreasing age (OR: 0.9 (95% CI: 0.93-0.99), P = 0.02) and a CD8/CD19 ratio >2.2 (OR: 10.3 (95% CI: 1.91-55.36), P = 0.007). Our data provide preliminary evidence that immune characterization of critically ill patients on ICU admission may help personalize the prediction of ensuing sepsis during their ICU stay. Further polycentric evaluation of the true potential of this new tool is warranted.
Altered peripheral lymphocyte subsets in untreated systemic lupus erythematosus patients with infections.
Lu Zhimin,Li Jing,Ji Juan,Gu Zhifeng,Da Zhanyun
Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas
The leading cause of death in systemic lupus erythematosus (SLE) patients is infection. The objective of this study was to evaluate the distribution of lymphocyte subsets in untreated SLE patients with infections. This was a cross-sectional study. Data from January 2017 to May 2018 were collected. Flow cytometry was used to measure the peripheral lymphocyte subsets including CD3+T cells, CD4+T cells, CD8+T cells, CD19+B cells, CD3-CD16+CD56NK cells, and CD3+CD16+CD56NKT cells in 25 healthy controls and 52 treatment-naive SLE patients, among whom 13 were complicated with infections. Association between the lymphocyte subsets and infections was further analyzed. SLE patients with infections (n=13) showed a significantly higher incidence rate of fever (84.6 vs 28.2%) and serositis (84.6 vs 23.1%), increased level of erythrocyte sedimentation rate (60.5±30.1 vs 37.4±27.1 mm/h), serum C-reactive protein (CRP) (102.7±94.9 vs 9.4±14.9 mg/L), procalcitonin (PCT) (1.07±0.08 vs 0.16±0.13 μg/L), and lower blood hemoglobin (Hb) (93.0±20.5 vs 110.4±16.0 g/L) level compared with non-infection patients (n=39) (all P<0.05). In comparison with non-infectious SLE patients (387.9±261.6/μL), CD4+T cells count decreased significantly in infectious SLE patients (217.8±150.4/μL) (P<0.05), and it was negatively correlated with infection-related indicators including PCT (r=-0.573, P=0.041) and CRP (r=-0.596, P=0.032) levels. Our findings suggested that abnormalities of peripheral lymphocyte subsets were related to the immune disorder of lupus itself, regardless of immunosuppressive treatment. Monitoring lymphocyte subsets, especially CD4+T cells, may be helpful for identifying the presence of infection in SLE patients.
Immunologic Monitoring of T-Lymphocyte Subsets and Hla-Dr-Positive Monocytes in Kidney Transplant Recipients: A Prospective, Observational Cohort Study.
Cho Jang-Hee,Yoon Young-Deuk,Jang Hye Min,Kwon Eugene,Jung Hee-Yeon,Choi Ji-Young,Park Sun-Hee,Kim Yong-Lim,Kim Hyung-Kee,Huh Seung,Won Dong-Il,Kim Chan-Duck
The clinical significance of circulating T-lymphocyte subsets and human leukocyte antigen (HLA)-DR-positive monocytes in the peripheral blood of kidney transplant recipients (KTRs) remains unclear. We examined the efficacy of enumerating these cells for the immunologic monitoring of KTRs.Blood samples were obtained before transplantation, 2 weeks after transplantation and at diagnosis, and 2 weeks after treating biopsy-proven acute cellular rejection and cytomegalovirus (CMV) infection. Serial flow cytometric analysis was performed using peripheral blood obtained from 123 patients to identify the frequencies of HLA-DR, CD3, CD4, CD8, and CD25 T-lymphocytes and HLA-DR-positive monocytes.Frequencies of CD4CD25/CD4 T cells, CD8CD25/CD8 T cells, and HLA-DR-positive monocytes were significantly lower at 2 weeks after transplantation than before transplantation (all P < 0.001). This decrease was not correlated with clinical parameters. The frequency of CD4CD25/CD4 T cells was significantly higher in KTRs with acute rejection than in KTRs at 2 weeks after transplantation (9.10% [range 4.30-25.6%] vs 5.10% [range 0.10-33.3%]; P = 0.024). However, no significant differences were observed between stable KTRs and KTRs with CMV infection. Analysis of the receiver operating characteristic curve adjusted by covariates showed that acute rejection could be predicted with 75.0% sensitivity and 68.4% specificity by setting the cutoff value of CD4CD25/CD4 T cell frequency as 5.8%.Circulating T-lymphocyte and monocyte subsets showed significant and consistent changes in their frequencies after immunosuppression. Of the various immune cells examined, circulating levels of CD4CD25 T cells might be a useful noninvasive immunologic indicator for detecting acute rejection.
The Systemic Lupus Erythematosus Infection Predictive Index (LIPI): A Clinical-Immunological Tool to Predict Infections in Lupus Patients.
Torres-Ruiz Jiram,Mejía-Domínguez Nancy R,Zentella-Dehesa Alejandro,Ponce-de-León Alfredo,Morales-Padilla Sandra Rubí,Vázquez-Rodríguez Ricardo,Alvarado-Lara Mario René,Reyna-de-la-Garza Roberto Adrián,Tapia-Rodríguez Miguel,Juárez-Vega Guillermo,Merayo-Chalico Javier,Barrera-Vargas Ana,Alcocer-Varela Jorge C,Gómez-Martín Diana
Frontiers in immunology
Among autoimmune diseases, systemic lupus erythematosus (SLE) patients have a unique predisposition to develop infections, which represents one of their main causes of morbidity and mortality. Many infections occur at disease diagnosis in the absence of immunosuppressive therapy, suggesting that the immunological abnormalities in SLE patients might be fundamental for the development of this complication. The aim of this study was to address the main clinical and immunological features associated with the development of infection and to create and validate a compound clinical-immunological infection predictive index in a cohort of SLE patients. We included 55 SLE patients with < 5 years since diagnosis. The clinical and immunological features were evaluated periodically and patients were followed-up during 1 year, searching for the development of infection. Immunophenotyping was performed by multiparametric flow cytometry and neutrophil extracellular traps (NETs) were assessed by confocal microscopy. Eighteen patients (32.7%) presented 19 infectious events, 5 (26.3%) were severe. For the construction of the index, we performed a logistic regression analysis and the cutoff points were determined with ROC curves. Increased numbers of peripheral Th17 cells, B cell lymphopenia, and lower TLR2 expression in monocytes, as well as the use of cyclophosphamide were the major risk factors for the development of infection and thus were included in the index. Besides, patients that developed infection were characterized by increased numbers of low-density granulocytes (LDGs) and higher expression of LL-37 in NETs upon infection. Finally, we validated the index retrospectively in a nested case-control study. A score >1.5 points was able to predict infection in the following year (AUC = 0.97; LR- = 0.001, specificity 100%, = 0.0003). Our index encompasses novel immunological features able to prospectively predict the risk of infection in SLE patients.
Association between lymphocyte subsets and cytomegalovirus infection status among patients with systemic lupus erythematosus: A pilot study.
Qin Ling,Qiu Zhifeng,Hsieh Evelyn,Geng Taoran,Zhao Jiuliang,Zeng Xiaofeng,Wan Lu,Xie Jing,Ramendra Rayoun,Routy Jean Pierre,Li Taisheng
This study aimed to determine the association between different lymphocyte subsets and cytomegalovirus (CMV) infection status in patients with systemic lupus erythematosus (SLE). We performed a retrospective study among SLE patients with CMV infection and collected patient socio-demographic and clinical characteristics, as well as their recorded circulating lymphocyte subsets. Univariate and multivariable logistic regression analyses examined the relationship between CMV infection status and lymphocyte subset counts. We included 125 hospitalized patients with SLE, consisting of 88 with documented CMV infection and 37 without any evidence of CMV or other infections. Among the 88 CMV-infected patients, 65 (73.8%) patients developed CMV disease and 23 (26.2%) presented as CMV viremia. Compared to uninfected patients (1520 ± 101 cells/μL), lymphocytes remained stable among those with CMV viremia (1305 ± 272 cells/μL, P = .995). However, compared to their uninfected counterparts, there was a marked decrease in lymphocytes among patients with CMV disease (680 ± 513 cells/μL, P < .001). Analysis of lymphocyte subsets via flow cytometry showed that CD4+ T cell, CD8+ T cell, and natural killer cell counts were lower among those with CMV disease compared to those with CMV viremia and those without infection. Further, multivariable analysis showed that total lymphocyte (odds ratio [OR] 0.999, 95% confidence interval [CI] 0.998-1.000, P = .007) and CD4+ T cell counts (OR 0.99, 95% CI 0.992-0.998, P = .003) were negatively associated with CMV disease. Our findings support a potential inverse relationship between lymphopenia, specifically CD4+ T-cell lymphopenia, and CMV disease among hospitalized SLE patients.