The association of neutrophil-lymphocyte ratio and lymphocyte-monocyte ratio with 3-month clinical outcome after mechanical thrombectomy following stroke.

BACKGROUND AND AIM: Neutrophil-lymphocyte ratio (NLR) and lymphocyte-monocyte ratio (LMR) are associated with clinical outcomes in malignancy, cardiovascular disease and stroke. Here we investigate their association with outcome after acute ischaemic stroke treated by mechanical thrombectomy (MT). METHODS: Patients were selected using audit data for MT for acute anterior circulation ischaemic stroke at a UK centre from May 2016-July 2017. Clinical and laboratory data including neutrophil, lymphocyte and monocyte count tested before and 24 h after MT were collected. Poor functional outcome was defined as modified Rankin Scale (mRS) of 3-6 at 3 months. Multivariable logistic regression analyses were performed to explore the relationship of NLR and LMR with functional outcome. RESULTS: One hundred twenty-one patients (mean age 66.4 ± 16.7, 52% female) were included. Higher NLR (adjusted OR 0.022, 95% CI, 0.009-0.34, p = 0.001) and lower LMR (adjusted OR - 0.093, 95% CI (- 0.175)-(- 0.012), p = 0.025) at 24-h post-MT were significantly associated with poorer functional outcome when controlling for age, baseline NIHSS score, infarct size, presence of good collateral supply, recanalisation and symptomatic intracranial haemorrhage on multivariate logistic regression. Admission NLR or LMR were not significant predictors of mRS at 3 months. The optimal cut-off values of NLR and LMR at 24-h post-MT that best discriminated poor outcome were 5.5 (80% sensitivity and 60% specificity) and 2.0 (80% sensitivity and 50% specificity), respectively on receiver operating characteristic curve analysis. CONCLUSION: NLR and LMR tested at 24 h after ictus or intervention may predict 3-month functional outcome.

Neutrophil-lymphocyte ratio is increased in elderly patients with first episode depression, but not in recurrent depression.

Association between inflammation and depression, especially in elderly patients, leads to conclusions about their shared influence on risk of cardiovascular disease and death. It might be found useful to predict those issues by monitoring inflammatory parameters, such as neutrophil/lymphocyte ratio (NLR). The aim of this study was to determine the NLR in elderly patients with unipolar depression compared with non-depressed elderly patients. NLR was measured in 684 Caucasian subjects (depressed: n = 465, non-depressed: n = 219), aged ≥ 60 (depressed: mean age 74.8 ±â€¯7.8 years, non-depressed: mean age: 71.1 ±â€¯5.7 years). There were two subgroups within depressed patients: first episode depression (n = 138, 29.6%) and recurrent depression (n = 328, 70.3%). NLR was calculated as ratio between absolute neutrophil count to absolute lymphocyte count. NLR was significantly higher in unmedicated patients with depression compared with healthy control (2.10 ±â€¯2.13 vs. 2.01 ±â€¯0.75, p = 0.004). It was higher in first episode depression compared with recurrent depression (2.11 ±â€¯1.76 vs 1.64 ±â€¯1.04, p < 0.05). There was a positive correlation with severity of symptoms. We found non-specific effect of treatment with antidepressants or antipsychotics on lower NLR. Increased NLR in patients with first episode of depression compared to recurrent depression and healthy control may have important clinical consequences. Severity of symptoms are positively correlated with NLR, which may indicate that with increasing severity of depression, the risk of cardiovascular events is also rising, which leads to higher mortality. In elderly patients with depression even a small reduction of such risk may translate into better prognosis and improve quality of live. The difference between first episode and recurrent depression in terms of inflammatory biomarkers requires further studies.

B-cell and T-cell quantification in minor salivary glands in primary Sjögren's syndrome: development and validation of a pixel-based digital procedure.

BACKGROUND: Evaluating lymphocytic infiltration of minor salivary gland biopsy in primary Sjögren's syndrome is challenging. We developed and evaluated a digital method for quantifying B and T lymphocytes in whole minor salivary gland biopsy slides. METHODS: Minor salivary gland biopsies were immunostained with anti-CD20/anti-CD3 antibodies using red/brown chromogens. Slides were digitised and spliced into mosaics of smaller JPEG format images in which red and brown pixels were counted. ImageJ Cell counter was used for validation. Agreement between the digital and manual methods was evaluated using Bland-Altman plots and the interclass correlation coefficient. External validation relied on the Chisholm-Mason, Tarpley, and focus-score methods. RESULTS: Of 62 minor salivary gland biopsy slides, 61.3 % had a Chisholm-Mason grade ≥ III or a focus score ≥1. The number of pixels correlated well with manual cell counts (r = 0.95 for red pixels vs. B cell count and r = 0.91 for brown pixels vs. T cell count). Interclass correlation coefficients between digital and manual counts were excellent (0.92 for B/T cells). B-cell proportion showed a significant positive correlation with the focus score (Spearman's coefficient 0.463, p < 0.0001). Median B-cell proportion was lower in minor salivary gland biopsies with Chisholm grades I-II (2.5 % (0.2-13.9)) than III-IV (30.0 % (15.5-45.2)) and increased with Tarpley's class (1, 2.2 % (0.2-6.6); 2, 27.2 % (13.0-38.9); and 3-4, 48.5 % (29.4-56.4); p < 0.001 for all comparisons). Minor salivary gland biopsy B-cell proportion was also significantly correlated with several markers of clinical and biological activity of the disease, especially with markers of systemic B-cell hyperactivation. CONCLUSION: The digital procedure proved accurate compared to the reference standard, producing reliable results for whole tissue sections. TRIAL REGISTRATION: ClinicalTrials.gov [ NCT00740948 ]. Registered 22 August 2008.

Utilidad del recuento e inmunofenotipaje de los linfocitos intraepiteliales de la mucosa intestinal en el diagnóstico de la enfermedad celiaca / Usefulness of intraepithelial lymphocytes immunophenotyping in intestinal mucosa for the diagnosis of coeliac disease

Introducción. Se han observado cambios característicos en las poblaciones de linfocitos intraepiteliales (LIE) de la mucosa intestinal en pacientes celiacos infantiles y adultos. Objetivos. Determinar el rango normal de las poblaciones de LIE por citometría de flujo y establecer su rentabilidad diagnóstica en la enfermedad celiaca (EC). Material y métodos. Estudio retrospectivo de 246 niños y 461 adultos con sospecha de EC a los que se había realizado estudio de poblaciones de LIE. El grupo de EC (221 niños y 98 adultos) lo forman individuos con serología celiaca positiva e histología con lesión grado Marsh 1 o mayor. El grupo control (25 niños y 363 adultos) lo constituyen individuos sin lesión intestinal y serología celiaca negativa a los que también se había realizado inmunofenotipo de LIE por citometría de flujo. Resultados. En el grupo de pacientes celiacos se observa un aumento significativo de LIE totales y LIE TCRγδ y un descenso significativo de LIE NK-like en comparación con los grupos control. En función de las curvas ROC, los puntos de corte en la población infantil fueron: %LIE > 14,2%, %LIE TCRγδ > 16,5% y %LIE NK-like < 10,1%. Los puntos de corte en la población adulta fueron: %LIE > 14,2%, %LIE TCRγδ > 16,1% y %LIE NK-like < 4,4%. En ambas poblaciones se obtienen una especificidad y VPP cercano o igual al 100%, con unos CP+ > 5 y CP− < 2 o próximos. Conclusiones. En el presente trabajo se han establecido los valores de corte para los tres parámetros analizados de los LIE. Estos parámetros permiten diagnosticar con una especificidad cercana al 100% la EC en el niño y en el adulto. Los valores de CP+ y CP− obtenidos muestran que estos parámetros son muy útiles en el diagnóstico de EC activa infantil y del adulto. Por lo tanto, el análisis de las poblaciones de LIE por medio de la citometría de flujo es una nueva herramienta diagnóstica de la EC que complementa el estudio anatomopatológico clásico aumentando su especificidad (AU)

Introduction: The intestinal mucosa of children and adult with coeliac disease shows characteristic changes in intraepithelial lymphocyte (IEL) populations. Objectives: Determination of the normal range of IEL populations by flow cytometry and its diagnostic usefulness in coeliac disease (CD). Methods: A retrospective study of 246 children and 461 adults with suspected CD with IEL immunophenotype results. The CD group (221 children and 98 adults) are individuals with positive coeliac serology and a histology lesion Marsh grade 1 or greater. The control group included 25 children and 363 adults without bowel lesion, negative serology and with IEL immunophenotype results. Results: The group of coeliac patients, adults and children, shows a significant increase in total IEL and TCRdeltagamma IEL, and a significant decrease in NK-like IEL compared with control groups. Based on ROC curves, the cut-off in coeliac children was: %IEL >14.2%, %TCRdeltagamma IEL>16.5% and %NK-like IEL<10.1%. The cut-off in the adult coeliac population was: %IEL >14.2%, %TCR IEL>16.1% and %NK-like IEL<4.4%. In both populations the specificity and PPV are close or equal to 100%, a CP+ >5 and a CP− <2 or near. Conclusions: The cut-off values of the LIE population analysed has been established in this study. The values of CP+ and CP− show that these parameters are very useful for the diagnosis of celiac disease in children and adults, with a specificity of approximately 100%. The immunophenotyping of LIE is a very useful technique in the diagnosis of CD, and complements the classical pathological study, thus increasing the specificity (AU)

A reversed CD4/CD8 ratio of tumor-infiltrating lymphocytes and a high percentage of CD4(+)FOXP3(+) regulatory T cells are significantly associated with clinical outcome in squamous cell carcinoma of the cervix.

In this study, 40 biopsy samples collected from cervical cancer patients at the First Affiliated Hospital of Xi'an Jiaotong University, China, were retrospectively assessed using immunohistochemistry for CD4(+) and CD8(+) tumor-infiltrating lymphocytes (TILs) and were analyzed for the expression of FOXP3, OX40, granzyme B (GrB) and perforin (Prf). The proliferating index of the TILs was determined by assessing Ki67 expression. We determined the prognostic value of low and high numbers of TILs on survival by performing Kaplan-Meier analysis using median values as the cut-off points. Except for the number of CD4(+)FOXP3(+) regulatory T cells (Tregs) and the CD4/CD8 ratio, none of the CD4(+), CD8(+), OX40(+), GrB(+) or Prf(+) TILs were associated with the overall 5-year survival rate. The 5-year survival rate was significantly lower in patients who had a high percentage of Tregs as compared with the those who had a lower percentage (35.3% versus 88.9%, P=0.001), while the 5-year survival rate was significantly higher in patients with a high CD4/CD8 ratio as compared with patients who had a low CD4/CD8 ratio (82.4% versus 44.4%, P=0.029). When we considered the deaths and surviving cases as separate groups, we found that both the number of CD4(+) T cells and the CD4/CD8 ratio were significantly lower in patients who died as compared with those who survived (26.33±11.80 versus 47.79±38.18, P=0.023 and 0.60±0.25 versus 1.17±1.02, P=0.019, respectively). In conclusion, decreased proportions of tumor-infiltrating CD4(+) T cells with high percentages of Tregs and reversed CD4/CD8 ratios were significantly associated with the clinical outcome of patients with cervical carcinoma.

Quantification of T-cell proliferation for individualizing immunosuppressive therapy for transplantation patients.

The serious side effects and complications related to the lifelong use of immunosuppressors in organ transplantation have fueled research into their possible minimization. Immunosuppressive therapy in organ transplantation is therefore tentatively moving from a phase of empirical administration toward individualized therapy. This process is highly dependent on the development of monitoring methods to detect individual immune states. The results of the studies by Kurata et al. support the usefulness of pharmacodynamic assays of lymphocyte function for the predictive monitoring of the effects of immunosuppressive drug therapy.

Is HIV becoming more virulent? Initial CD4 cell counts among HIV seroconverters during the course of the HIV epidemic: 1985-2007.

BACKGROUND: Whether human immunodeficiency virus (HIV) seroconverters have been presenting with progressively lower CD4 cell counts over the course of the HIV epidemic is controversial. Additional data on whether HIV might have become more virulent on a population level (measured by post-seroconversion CD4 cell counts) may provide important insights regarding HIV pathogenesis. METHODS: To determine whether post-seroconversion CD4 cell counts have changed over time, we evaluated 2174 HIV seroconverters as part of a large cohort study during the period 1985-2007. Participants were documented antiretroviral-naive HIV seroconverters who had a CD4 cell count measured within 6 months after receiving a diagnosis of HIV infection. Multiple linear regression models were used to assess trends in initial CD4 cell counts. RESULTS: The mean initial CD4 cell count decreased during the study period from 632 cells/mm(3) in 1985-1990 to 553 cells/mm(3) in 1991-1995, 493 cells/mm(3) in 1996-2001, and 514 cells/mm(3) in 2002-2007. During those periods, the percentages of seroconverters with an initial CD4 cell count <350 cells/mm(3) were 12%, 21%, 26%, and 25%, respectively. In the multiple linear model, the mean decrease in CD4 cell count from 1985-1990 was 65 cells/mm(3) in 1991-1995 (P < .001)), 107 cells/mm(3) in 1996-2001 (P < .001), and 102 cells/mm(3) in 2002-2007 (P < .001). Similar trends occurred with regard to CD4 cell percentage and total lymphocyte count. Similar decreases in initial CD4 cell counts were observed among African American and white persons during the epidemic. DISCUSSION: A significant decrease in initial CD4 cell counts among HIV seroconverters in the United States has occurred during the HIV epidemic. These data provide an important clinical correlate to suggestions that HIV may have adapted to the host, resulting in a more virulent infection.

Clinical relevance of the severe abnormalities of the T cell compartment in septic shock patients.

INTRODUCTION: Given the pivotal role of T lymphocytes in the immune system, patients with septic shock may show T cell abnormalities. We have characterised the T cell compartment in septic shock and assess its clinical implications. METHODS: T lymphocytes from the peripheral blood of 52 patients with septic shock and 36 healthy control subjects were analysed on admission to the intensive care unit, baseline, and 3, 7, 14 and 28 days later. T cell phenotypes (CD3+CD4+/CD3+CD8+, CD45RA+/CD45RO+, CD62L+/CD28+) were assessed by quantitative flow cytometry. RESULTS: CD3+, CD3+CD4+ and CD3+CD8+ lymphocyte counts were significantly lower in patients with septic shock than control subjects. In surviving patients, CD3+CD4+ lymphocytes had normalised after 14 days, yet CD3+CD8+ numbers were still low. Non effector CD45RA+CD45RO- subsets of CD3+CD4+ and CD3+CD8+ were persistently low during patient follow up. CD3+CD8+CD28+ and CD3+CD8+CD62L+ were reduced in patients versus controls and survivors versus nonsurvivors in the first three days. A prediction receptor operative curve revealed that for the CD3+CD8+CD28+ subset, a cutoff of 136 cells/ml showed 70% sensitivity and 100% specificity for predicting death and the area under the curve was 0.84 at admission. Corresponding values for CD3+CD8+CD62L+ were 141 cells/ml, 60% sensitivity, 100% specificity and an area under the curve of 0.75. CONCLUSIONS: A severe redistribution of T lymphocyte subsets is found in septic shock patients. A different kinetic pattern of T cell subset involvement is observed in surviving and nonsurviving patients, with lower numbers of circulating CD3+CD8+CD28+ and CD3+CD8+CD62L+ associated with a better disease outcome.

The search for a predictor of CD4 cell count continues: total lymphocyte count is not a substitute for CD4 cell count in the management of HIV-infected individuals in a resource-limited setting.

Total lymphocyte count (TLC) has been recommended as a substitute for CD4 cell count for the management of HIV-infected individuals living in resource-limited settings. To confirm this, 151 TLCs and CD4 cell counts were obtained from 109 patients who had not yet started treatment and analyzed. CD4 cell counts of <200 cells/mm3 were found in 42 cases (37.8%) with TLCs of > or =1200 cells/mm3. Thus, 1 in 3 individuals would have been deprived of needed treatment. Therefore, in this setting, TLC is not a reliable predictor of CD4 cell count in HIV-infected individuals.