Peripheral blood lymphocyte subpopulations in patients with bipolar disorder type II

Pietruczuk, Krzysztof; Lisowska, Katarzyna A.; Grabowski, Karol; Landowski, Jerzy; Cubała, Wiesław Jerzy; Witkowski, Jacek M.

doi:10.1038/s41598-019-42482-6

Cited by 24 publications

(19 citation statements)

References 33 publications

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“…Increased CD14 + levels in serum and cerebrospinal fluid (CSF) have also been associated with schizophrenia and bipolar disorder risk ( Jakobsson et al, 2015 ; Johansson et al, 2017 ). Similarly, for the other immune cell types implicated in the MSEA analysis of miRNA blood-brain correlates, significant aberrations in cell subpopulation levels have been reported for various neurological and psychiatric conditions, both in brain tissue ( Busse et al, 2012 ; Geng and Huang, 2021 ; Troscher et al, 2021 ) and peripheral blood samples ( Schleifer et al, 2002 ; Richartz-Salzburger et al, 2007 ; Miller et al, 2013 ; Cacabelos et al, 2016 ; Rocha et al, 2018 ; Furlan et al, 2019 ; Pietruczuk et al, 2019 ), including major depression, schizophrenia, epilepsy, bipolar disorder and Parkinson’s disease, among others, further suggesting a broad, pathophysiological role for changes in inflammation profiles.…”

Section: Discussionmentioning

confidence: 76%

Blood-Based miRNA Biomarkers as Correlates of Brain-Based miRNA Expression

Kos

Puppala

Cruz

et al. 2022

Front. Mol. Neurosci.

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The use of easily accessible peripheral samples, such as blood or saliva, to investigate neurological and neuropsychiatric disorders is well-established in genetic and epigenetic research, but the pathological implications of such biomarkers are not easily discerned. To better understand the relationship between peripheral blood- and brain-based epigenetic activity, we conducted a pilot study on captive baboons (Papio hamadryas) to investigate correlations between miRNA expression in peripheral blood mononuclear cells (PBMCs) and 14 different cortical and subcortical brain regions, represented by two study groups comprised of 4 and 6 animals. Using next-generation sequencing, we identified 362 miRNAs expressed at ≥ 10 read counts in 80% or more of the brain samples analyzed. Nominally significant pairwise correlations (one-sided P < 0.05) between peripheral blood and mean brain expression levels of individual miRNAs were observed for 39 and 44 miRNAs in each group. When miRNA expression levels were averaged for tissue type across animals within the groups, Spearman’s rank correlations between PBMCs and the brain regions are all highly significant (rs = 0.47–0.57; P < 2.2 × 10–16), although pairwise correlations among the brain regions are markedly stronger (rs = 0.86–0.99). Principal component analysis revealed differentiation in miRNA expression between peripheral blood and the brain regions for the first component (accounting for ∼75% of variance). Linear mixed effects modeling attributed most of the variance in expression to differences between miRNAs (>70%), with non-significant 7.5% and 13.1% assigned to differences between blood and brain-based samples in the two study groups. Hierarchical UPGMA clustering revealed a major co-expression branch in both study groups, comprised of miRNAs globally upregulated in blood relative to the brain samples, exhibiting an enrichment of miRNAs expressed in immune cells (CD14+, CD15+, CD19+, CD3+, and CD56 + leukocytes) among the top blood-brain correlates, with the gene MYC, encoding a master transcription factor that regulates angiogenesis and neural stem cell activation, representing the most prevalent miRNA target. Although some differentiation was observed between tissue types, these preliminary findings reveal wider correlated patterns between blood- and brain-expressed miRNAs, suggesting the potential utility of blood-based miRNA profiling for investigating by proxy certain miRNA activity in the brain, with implications for neuroinflammatory and c-Myc-mediated processes.

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Section: Discussionmentioning

confidence: 76%

Blood-Based miRNA Biomarkers as Correlates of Brain-Based miRNA Expression

Kos

Puppala

Cruz

et al. 2022

Front. Mol. Neurosci.

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“…Mays et al investigated whether the number or percentage of B cells reflected depressive states and noticed that depressed patients had significantly higher numbers of CD19 + B cells compared to HCs ( 30 ). A recent study that compared BD patients with HCs on distribution of B lymphocyte subsets yielded a similar result: patients with BD who were in remission and depressive episodes had a higher percentage of CD19 + B cells than HCs ( 31 ). The last but not least, Benschop et al showed that acute psychological stress induces a transient increase in lymphocyte numbers, with NK cell counts being the most prominent ( 32 ); on the contrary, Patas et al discovered that decreased NK cell counts were observed in patients with MDD ( 33 , 34 ).…”

Section: Introductionmentioning

confidence: 74%

Development and validation of a nomogram based on lymphocyte subsets to distinguish bipolar depression from major depressive disorder

Shuai

Mou

et al. 2022

Front. Psychiatry

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ObjectiveBipolar depression (BD) and major depressive disorder (MDD) are both common affective disorders. The common depression episodes make it difficult to distinguish between them, even for experienced clinicians. Failure to properly diagnose them in a timely manner leads to inappropriate treatment strategies. Therefore, it is important to distinguish between BD and MDD. The aim of this study was to develop and validate a nomogram model that distinguishes BD from MDD based on the characteristics of lymphocyte subsets.Materials and methodsA prospective cross-sectional study was performed. Blood samples were obtained from participants who met the inclusion criteria. The least absolute shrinkage and selection operator (LASSO) regression model was used for factor selection. A differential diagnosis nomogram for BD and MDD was developed using multivariable logistic regression and the area under the curve (AUC) with 95% confidence interval (CI) was calculated, as well as the internal validation using a bootstrap algorithm with 1,000 repetitions. Calibration curve and decision curve analysis (DCA) were used to evaluate the calibration and clinical utility of the nomogram, respectively.ResultsA total of 166 participants who were diagnosed with BD (83 cases) or MDD (83 cases), as well as 101 healthy controls (HCs) between June 2018 and January 2022 were enrolled in this study. CD19+ B cells, CD3+ T cells, CD3–CD16/56+ NK cells, and total lymphocyte counts were strong predictors of the diagnosis of BD and MDD and were included in the differential diagnosis nomogram. The AUC of the nomogram and internal validation were 0.922 (95%; CI, 0.879–0.965), and 0.911 (95% CI, 0.838–0.844), respectively. The calibration curve used to discriminate BD from MDD showed optimal agreement between the nomogram and the actual diagnosis. The results of DCA showed that the net clinical benefit was significant.ConclusionThis is an easy-to-use, repeatable, and economical nomogram for differential diagnosis that can help clinicians in the individual diagnosis of BD and MDD patients, reduce the risk of misdiagnosis, facilitate the formulation of appropriate treatment strategies and intervention plans.

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“…The preservation of lymphocyte subpopulations is one of the key steps when studying different types of hematological and immunological disorders [15, 16]. To this aim, in a select group of 19 subjects, we evaluated the ability of the automatic stratification method to guarantee correct recovery of the most representative lymphoid subsets.…”

Section: Resultsmentioning

confidence: 99%

Purification of viable peripheral blood mononuclear cells for biobanking using a robotized liquid handling workstation

et al. 2019

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BackgroundThe purification of peripheral blood mononuclear cells (PBMCs) by means of density gradient (1.07 g/mL) centrifugation is one of the most commonly used methods in diagnostics and research laboratories as well as in biobanks. Here, we evaluated whether it was possible to set up an automated protocol for PBMC purification using a programmable liquid handling robotized workstation (Tecan, Freedom EVO 150). We selected a population composed of 30 subjects for whom it was possible to dispose of two ethylenediaminetetraacetic acid (EDTA) vacutainer tubes containing unfractionated peripheral blood. The purification of PBMCs was performed in parallel using automated and manual workflows.ResultsAn automated workflow using the Freedom EVO 150 liquid handling workstation was generated for the isolation of PBMCs. This protocol allowed blood dilution in Dulbecco’s phosphate-buffered saline (DPBS), stratification onto the density gradient, and the collection of PBMC rings after centrifugation. The comparison between the automated and manual methods revealed no significant differences after separation in terms of total mononuclear cell enrichment, red blood cell contamination, or leucocyte formula, including the percentage of lymphoid subpopulations as B, T and natural killer (NK) lymphocytes.ConclusionsOur results show that it is possible to set up an automated protocol for the isolation of PBMCs using a robotized liquid handling workstation. This automated protocol provided comparable results to the routinely used manual method. This automatic method could be of interest for those working in biobanking or industries involved in diagnostics and therapeutics field, to avoid operator-dependent errors as well as procedures standardization.

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Peripheral blood lymphocyte subpopulations in patients with bipolar disorder type II

Cited by 24 publications

References 33 publications

Blood-Based miRNA Biomarkers as Correlates of Brain-Based miRNA Expression

Blood-Based miRNA Biomarkers as Correlates of Brain-Based miRNA Expression

Development and validation of a nomogram based on lymphocyte subsets to distinguish bipolar depression from major depressive disorder

Purification of viable peripheral blood mononuclear cells for biobanking using a robotized liquid handling workstation

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