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1.
J Clin Immunol ; 44(6): 142, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38847943

RESUMO

PURPOSE: Common Variable Immunodeficiency (CVID) is characterized by hypogammaglobulinemia and failure of specific antibody production due to B-cell defects. However, studies have documented various T-cell abnormalities, potentially linked to viral complications. The frequency of Cytomegalovirus (CMV) replication in CVID cohorts is poorly studied. To address this gap in knowledge, we set up an observational study with the objectives of identifying CVID patients with active viraemia (CMV, Epstein-Barr virus (EBV)), evaluating potential correlations with immunophenotypic characteristics, clinical outcome, and the dynamic progression of clinical phenotypes over time. METHODS: 31 CVID patients were retrospectively analysed according to viraemia, clinical and immunologic characteristics. 21 patients with non CVID humoral immunodeficiency were also evaluated as control. RESULTS: Active viral replication of CMV and/or EBV was observed in 25% of all patients. CMV replication was detected only in CVID patients (16%). CVID patients with active viral replication showed reduced HLA-DR+ NK counts when compared with CMV-DNA negative CVID patients. Viraemic patients had lower counts of LIN-DNAMbright and LIN-CD16+ inflammatory lymphoid precursors which correlated with NK-cell subsets. Analysis of the dynamic progression of CVID clinical phenotypes over time, showed that the initial infectious phenotype progressed to complicated phenotypes with time. All CMV viraemic patients had complicated disease. CONCLUSION: Taken together, an impaired production of inflammatory precursors and NK activation is present in CVID patients with active viraemia. Since "Complicated" CVID occurs as a function of disease duration, there is need for an accurate evaluation of this aspect to improve classification and clinical management of CVID patients.


Assuntos
Imunodeficiência de Variável Comum , Infecções por Citomegalovirus , Citomegalovirus , Herpesvirus Humano 4 , Replicação Viral , Humanos , Imunodeficiência de Variável Comum/imunologia , Imunodeficiência de Variável Comum/complicações , Masculino , Feminino , Infecções por Citomegalovirus/imunologia , Citomegalovirus/imunologia , Citomegalovirus/fisiologia , Adulto , Pessoa de Meia-Idade , Herpesvirus Humano 4/fisiologia , Herpesvirus Humano 4/imunologia , Estudos Retrospectivos , Células Matadoras Naturais/imunologia , Adulto Jovem , Viremia/imunologia , Infecções por Vírus Epstein-Barr/imunologia , Imunofenotipagem , Idoso , Adolescente
2.
Front Immunol ; 15: 1400550, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38835756

RESUMO

The dog is an important companion animal and also serves as model species for human diseases. Given the central role of T cells in immune responses, a basic understanding of canine conventional T cell receptor (TCR)αß+ T cells, comprising CD4+ single-positive (sp) T helper (Th) and CD8α+ sp cytotoxic T cell subsets, is available. However, characterization of canine non-conventional TCRαß+ CD4+CD8α+ double-positive (dp) and TCRαß+ CD4-CD8α- double-negative (dn) T cells is limited. In this study, we performed a comprehensive analysis of canine dp and dn T cells in comparison with their conventional counterparts. TCRαß+ T cells from peripheral blood of healthy dogs were sorted according to their CD4/CD8α phenotype into four populations (i.e. CD4+ sp, CD8α+ sp, dp, and dn) and selected surface markers, transcription factors and effector molecules were analyzed ex vivo and after in vitro stimulation by RT-qPCR. Novel characteristics of canine dp T cells were identified, expanding the previously characterized Th1-like phenotype to Th17-like and Th2-like properties. Overall, mRNA expression of various Th cell-associated cytokines (i.e. IFNG, IL17A, IL4, IL13) in dp T cells upon stimulation highlights their versatile immunological potential. Furthermore, we demonstrated that the CD4-CD8α- dn phenotype is stable during in vitro stimulation. Strikingly, dn T cells were found to express highest mRNA levels of type 2 effector cytokines (IL4, IL5, and IL13) upon stimulation. Their strong ability to produce IL-4 was confirmed at the protein level. Upon stimulation, the percentage of IL-4-producing cells was even higher in the non-conventional dn than in the conventional CD4+ sp population. Constitutive transcription of IL1RL1 (encoding IL-33Rα) further supports Th2-like properties within the dn T cell population. These data point to a role of dn T cells in type 2 immunity. In addition, the high potential of dn T cells to transcribe the gene encoding the co-inhibitory receptor CTLA-4 and to produce the inhibitory cytokine IL-10 indicates putative immunosuppressive capacity of this population. In summary, this study reveals important novel aspects of canine non-conventional T cells providing the basis for further studies on their effector and/or regulatory functions to elucidate their role in health and disease.


Assuntos
Receptores de Antígenos de Linfócitos T alfa-beta , Células Th2 , Animais , Cães , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Células Th2/imunologia , Antígenos CD8/metabolismo , Antígenos CD8/imunologia , Citocinas/metabolismo , Antígenos CD4/metabolismo , Antígenos CD4/imunologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Imunofenotipagem , Masculino
3.
Front Immunol ; 15: 1402724, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38835783

RESUMO

Background and objective: Acute ischemic stroke (AIS) is a leading cause of mortality, severe neurological and long-term disability world-wide. Blood-based indicators may provide valuable information on identified prognostic factors. However, currently, there is still a lack of peripheral blood indicators for the prognosis of AIS. We aimed to identify the most promising prognostic indicators and establish prognostic models for AIS. Methods: 484 subjects enrolled from four centers were analyzed immunophenotypic indicators of peripheral blood by flow cytometry. Least absolute shrinkage and selection operator (LASSO) regression was applied to minimize the potential collinearity and over-fitting of variables measured from the same subject and over-fitting of variables. Univariate and multivariable Cox survival analysis of differences between and within cohorts was performed by log-rank test. The areas under the receiving operating characteristic (ROC) curves were used to evaluate the selection accuracy of immunophenotypic indicators in identifying AIS subjects with survival risk. The prognostic model was constructed using a multivariate Cox model, consisting of 402 subjects as a training cohort and 82 subjects as a testing cohort. Results: In the prospective study, 7 immunophenotypic indicators of distinct significance were screened out of 72 peripheral blood immunophenotypic indicators by LASSO. In multivariate cox regression, CTL (%) [HR: 1.18, 95% CI: 1.03-1.33], monocytes/µl [HR: 1.13, 95% CI: 1.05-1.21], non-classical monocytes/µl [HR: 1.09, 95% CI: 1.02-1.16] and CD56high NK cells/µl [HR: 1.13, 95% CI: 1.05-1.21] were detected to decrease the survival probability of AIS, while Tregs/µl [HR:0.97, 95% CI: 0.95-0.99, p=0.004], BM/µl [HR:0.90, 95% CI: 0.85-0.95, p=0.023] and CD16+NK cells/µl [HR:0.93, 95% CI: 0.88-0.98, p=0.034] may have the protective effect. As for indicators' discriminative ability, the AUC for CD56highNK cells/µl attained the highest of 0.912. In stratification analysis, the survival probability for AIS subjects with a higher level of Tregs/µl, BM/µl, CD16+NK cells/µl, or lower levels of CD56highNK cells/µl, CTL (%), non-classical monocytes/µl, Monocytes/µl were more likely to survive after AIS. The multivariate Cox model showed an area under the curve (AUC) of 0.805, 0.781 and 0.819 and 0.961, 0.924 and 0.982 in the training and testing cohort, respectively. Conclusion: Our study identified 7 immunophenotypic indicators in peripheral blood may have great clinical significance in monitoring the prognosis of AIS and provide a convenient and valuable predictive model for AIS.


Assuntos
Citometria de Fluxo , Imunofenotipagem , AVC Isquêmico , Humanos , Feminino , Masculino , AVC Isquêmico/sangue , AVC Isquêmico/mortalidade , AVC Isquêmico/diagnóstico , AVC Isquêmico/imunologia , Citometria de Fluxo/métodos , Prognóstico , Idoso , Pessoa de Meia-Idade , Estudos Prospectivos , Biomarcadores/sangue , Idoso de 80 Anos ou mais
4.
Indian J Public Health ; 68(1): 21-25, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38847628

RESUMO

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Immunophenotype (IPT) and cytogenetics are essential for diagnosis, risk stratification, and management for ALL. OBJECTIVES: Evaluating the burden of immunophenotypic and cytogenetic profile of pediatric ALL patients. MATERIALS AND METHODS: A descriptive cross-sectional study was conducted on 100 patients of ALL (1-18 completed years) attending a tertiary-care center in Kolkata, Eastern India. RESULTS: Ninety-six percent of patients had B-cell ALL (94.00% pre-B ALL and 2.00% Pro-B ALL) and 4.0% had T-ALL. 60% B-cell ALL were CD19/CD10 positive, 10% were CD79a positive, 9% were only CD19 positive, and 7% were only CD10 positive. Thirty-three percent of T-ALL were CD3+, whereas 22% were positive each for CD4 and CD7. 51.0% of patients had diploid, 46.0% hyperdiploid, and 3.0% hypodiploid karyotype. Among hyperdiploids, 98% had good prednisolone response and 89% had measurable residual disease (MRD) <0.01. CONCLUSION: The most commonly diagnosed ALL by IPT was pre-B ALL. Among the detectable cytogenetic abnormalities, t(12; 21) ETV6-RUNX1 was the most common. ZNF-384 gene arrangement was also detected in our study. t(12;21) ETV6-RUNX1 had a good treatment response, while t(9;22) BCR-ABL, t(1;19) TCF3-PBX1, iAMP-21, MLL gene rearrangement, and ZNF-384 gene arrangement had poor treatment response in terms of MRD.


Assuntos
Imunofenotipagem , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Índia/epidemiologia , Criança , Masculino , Feminino , Pré-Escolar , Adolescente , Estudos Transversais , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Lactente , Análise Citogenética
6.
BMC Infect Dis ; 24(1): 567, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844850

RESUMO

This study investigates the longitudinal dynamic changes in immune cells in COVID-19 patients over an extended period after recovery, as well as the interplay between immune cells and antibodies. Leveraging single-cell mass spectrometry, we selected six COVID-19 patients and four healthy controls, dissecting the evolving landscape within six months post-viral RNA clearance, alongside the levels of anti-spike protein antibodies. The T cell immunophenotype ascertained via single-cell mass spectrometry underwent validation through flow cytometry in 37 samples. Our findings illuminate that CD8 + T cells, gamma-delta (gd) T cells, and NK cells witnessed an increase, in contrast to the reduction observed in monocytes, B cells, and double-negative T (DNT) cells over time. The proportion of monocytes remained significantly elevated in COVID-19 patients compared to controls even after six-month. Subpopulation-wise, an upsurge manifested within various T effector memory subsets, CD45RA + T effector memory, gdT, and NK cells, whereas declines marked the populations of DNT, naive and memory B cells, and classical as well as non-classical monocytes. Noteworthy associations surfaced between DNT, gdT, CD4 + T, NK cells, and the anti-S antibody titer. This study reveals the changes in peripheral blood mononuclear cells of COVID-19 patients within 6 months after viral RNA clearance and sheds light on the interactions between immune cells and antibodies. The findings from this research contribute to a better understanding of immune transformations during the recovery from COVID-19 and offer guidance for protective measures against reinfection in the context of viral variants.


Assuntos
COVID-19 , Citometria de Fluxo , Leucócitos Mononucleares , RNA Viral , SARS-CoV-2 , Humanos , COVID-19/imunologia , COVID-19/sangue , COVID-19/virologia , Leucócitos Mononucleares/virologia , Leucócitos Mononucleares/imunologia , SARS-CoV-2/imunologia , Masculino , Feminino , Pessoa de Meia-Idade , RNA Viral/sangue , Adulto , Estudos Longitudinais , Análise de Célula Única/métodos , Células Matadoras Naturais/imunologia , Anticorpos Antivirais/sangue , Imunofenotipagem , Idoso
7.
Zhonghua Bing Li Xue Za Zhi ; 53(6): 563-569, 2024 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-38825901

RESUMO

Objective: To analyze the clinicopathological features and differential diagnosis of large B-cell lymphoma with IRF4 rearrangement, aiming enhance its recognition and prevent misdiagnosis. Methods: The clinicopathological features, immunophenotype, and fluorescence in situ hybridization (FISH) results of six cases diagnosed with IRF4 rearrangement-positive B-cell lymphoma at the Affiliated Hospital of Xuzhou Medical University from 2015 to 2023 were retrospectively analyzed. Additionally, a comprehensive review of the literature was conducted. Results: Six patients with IRF4 rearrangement-positive large B-cell lymphoma were included. Patients 1 to 5 included three males and two females with a median age of 19 years ranging from 11 to 34 years. Four patients presented with head and neck lesions, while the other one had a breast nodule; all were in clinical Ann Arbor stages I to Ⅱ. Morphologically, entirely diffuse pattern was present in two cases, purely follicular pattern in one case, and diffuse and follicular patterns in other two cases. The tumor cells, predominantly centroblasts mixed with some irregular centrocytes, were of medium to large size, with a starry sky appearance observed in two cases. Immunophenotyping revealed all cases were positive for bcl-6 and MUM1, with a Ki-67 index ranging from 70% to 90%, and CD10 was positive in two cases. IRF4 rearrangement was confirmed in all cases by FISH analysis, with dual IRF4/bcl-6 rearrangements identified in two cases, leading to a diagnosis of LBCL-IRF4. Case 6, a 39-year-old female with a tonsillar mass and classified as clinical Ann Arbor stage Ⅳ, displayed predominantly diffuse large B-cell lymphoma (DLBCL) morphology with 20% high-grade follicular lymphoma characteristics. Immunohistochemistry showed negative CD10 and positive bcl-6/MUM1, with a Ki-67 index of approximately 80%. Triple rearrangements of IRF4/bcl-2/bcl-6 were identified by FISH, leading to a diagnosis of DLBCL with 20% follicular lymphoma (FL). All six patients achieved complete remission after treatment, with no progression or relapse during a follow-up period of 31-100 months. Conclusions: Large B-cell lymphoma with IRF4 rearrangement is a rare entity with pathological features that overlap with those of FL and DLBCL. While IRF4 rearrangement is necessary for diagnosing LBCL-IRF4, it is not specific and requires differentiation from other aggressive B-cell lymphomas with IRF4 rearrangement.


Assuntos
Rearranjo Gênico , Hibridização in Situ Fluorescente , Fatores Reguladores de Interferon , Linfoma Difuso de Grandes Células B , Proteínas Proto-Oncogênicas c-bcl-6 , Humanos , Fatores Reguladores de Interferon/genética , Fatores Reguladores de Interferon/metabolismo , Diagnóstico Diferencial , Feminino , Masculino , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/metabolismo , Adulto , Adolescente , Estudos Retrospectivos , Proteínas Proto-Oncogênicas c-bcl-6/genética , Proteínas Proto-Oncogênicas c-bcl-6/metabolismo , Criança , Adulto Jovem , Imunofenotipagem , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
10.
Transl Psychiatry ; 14(1): 254, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38866753

RESUMO

Depression is a prevalent and incapacitating condition with a significant impact on global morbidity and mortality. Although the immune system's role in its pathogenesis is increasingly recognized, there is a lack of comprehensive understanding regarding the involvement of innate and adaptive immune cells. To address this gap, we conducted a multicenter case-control study involving 121 participants matched for sex and age. These participants had either an active (or current) major depressive episode (MDE) (39 cases) or a remitted MDE (40 cases), including individuals with major depressive disorder or bipolar disorder. We compared these 79 patients to 42 healthy controls (HC), analyzing their immunological profiles. In blood samples, we determined the complete cell count and the monocyte subtypes and lymphocyte T-cell populations using flow cytometry. Additionally, we measured a panel of cytokines, chemokines, and neurotrophic factors in the plasma. Compared with HC, people endorsing a current MDE showed monocytosis (p = 0.001), increased high-sensitivity C-reactive protein (p = 0.002), and erythrocyte sedimentation rate (p = 0.003), and an altered proportion of specific monocyte subsets. CD4 lymphocytes presented increased median percentages of activation markers CD69+ (p = 0.007) and exhaustion markers PD1+ (p = 0.013) and LAG3+ (p = 0.014), as well as a higher frequency of CD4+CD25+FOXP3+ regulatory T cells (p = 0.003). Additionally, patients showed increased plasma levels of sTREM2 (p = 0.0089). These changes are more likely state markers, indicating the presence of an ongoing inflammatory response during an active MDE. The Random Forest model achieved remarkable classification accuracies of 83.8% for MDE vs. HC and 70% for differentiating active and remitted MDE. Interestingly, the cluster analysis identified three distinct immunological profiles among MDE patients. Cluster 1 has the highest number of leukocytes, mainly given by the increment in lymphocyte count and the lowest proinflammatory cytokine levels. Cluster 3 displayed the most robust inflammatory pattern, with high levels of TNFα, CX3CL1, IL-12p70, IL-17A, IL-23, and IL-33, associated with the highest level of IL-10, as well as ß-NGF and the lowest level for BDNF. This profile is also associated with the highest absolute number and percentage of circulating monocytes and the lowest absolute number and percentage of circulating lymphocytes, denoting an active inflammatory process. Cluster 2 has some cardinal signs of more acute inflammation, such as elevated levels of CCL2 and increased levels of proinflammatory cytokines such as IL-1ß, IFNγ, and CXCL8. Similarly, the absolute number of monocytes is closer to a HC value, as well as the percentage of lymphocytes, suggesting a possible initiation of the inflammatory process. The study provides new insights into the immune system's role in MDE, paving the ground for replication prospective studies targeting the development of diagnostic and prognostic tools and new therapeutic targets.


Assuntos
Citocinas , Transtorno Depressivo Maior , Imunofenotipagem , Monócitos , Humanos , Feminino , Masculino , Estudos de Casos e Controles , Transtorno Depressivo Maior/imunologia , Transtorno Depressivo Maior/sangue , Adulto , Pessoa de Meia-Idade , Citocinas/sangue , Citocinas/imunologia , Monócitos/imunologia , Transtorno Bipolar/imunologia , Transtorno Bipolar/sangue , Inflamação/imunologia , Inflamação/sangue , Antígenos CD/sangue , Antígenos CD/imunologia , Citometria de Fluxo
11.
Breast Cancer Res ; 26(1): 97, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858721

RESUMO

BACKGROUND: Tumor immune infiltration and peripheral blood immune signatures have prognostic and predictive value in breast cancer. Whether distinct peripheral blood immune phenotypes are associated with response to neoadjuvant chemotherapy (NAC) remains understudied. METHODS: Peripheral blood mononuclear cells from 126 breast cancer patients enrolled in a prospective clinical trial (NCT02022202) were analyzed using Cytometry by time-of-flight with a panel of 29 immune cell surface protein markers. Kruskal-Wallis tests or Wilcoxon rank-sum tests were used to evaluate differences in immune cell subpopulations according to breast cancer subtype and response to NAC. RESULTS: There were 122 evaluable samples: 47 (38.5%) from patients with hormone receptor-positive, 39 (32%) triple-negative (TNBC), and 36 (29.5%) HER2-positive breast cancer. The relative abundances of pre-treatment peripheral blood T, B, myeloid, NK, and unclassified cells did not differ according to breast cancer subtype. In TNBC, higher pre-treatment myeloid cells were associated with lower pathologic complete response (pCR) rates. In hormone receptor-positive breast cancer, lower pre-treatment CD8 + naïve and CD4 + effector memory cells re-expressing CD45RA (TEMRA) T cells were associated with more extensive residual disease after NAC. In HER2 + breast cancer, the peripheral blood immune phenotype did not differ according to NAC response. CONCLUSIONS: Pre-treatment peripheral blood immune cell populations (myeloid in TNBC; CD8 + naïve T cells and CD4 + TEMRA cells in luminal breast cancer) were associated with response to NAC in early-stage TNBC and hormone receptor-positive breast cancers, but not in HER2 + breast cancer. TRIAL REGISTRATION: NCT02022202 . Registered 20 December 2013.


Assuntos
Neoplasias da Mama , Imunofenotipagem , Terapia Neoadjuvante , Humanos , Feminino , Terapia Neoadjuvante/métodos , Pessoa de Meia-Idade , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/imunologia , Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Adulto , Idoso , Receptor ErbB-2/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucócitos Mononucleares/metabolismo , Biomarcadores Tumorais/sangue , Prognóstico , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/imunologia , Neoplasias de Mama Triplo Negativas/sangue , Neoplasias de Mama Triplo Negativas/patologia , Estudos Prospectivos , Resultado do Tratamento , Quimioterapia Adjuvante/métodos
12.
Sci Rep ; 14(1): 13452, 2024 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-38862612

RESUMO

In recent years, the significance of detecting minimal/measurable residual disease (MRD) in chronic lymphocytic leukemia (CLL) has increased due to the availability of highly effective therapeutic agents. Flow cytometry provides notable cost-effectiveness and immediacy, with an expected sensitivity level of approximately 10-4. The critical aspect of MRD detection via flow cytometry lies in accurately defining the region containing tumor cells. However, a subset of CLL, known as CLL with atypical immunophenotype, exhibits a distinct cell surface marker expression pattern that can make MRD detection challenging, because these markers often resemble those of normal B cells. To enhance the sensitivity of MRD detection in such atypical cases of CLL, we have capitalized on the observation that cell surface immunoglobulin (sIg) light chains tend to be expressed at a higher level in this subtype. For every four two-dimensional plots of cell surface markers, we used a plot to evaluate the expression of sIg kappa/lambda light chains and identified regions where the kappa/lambda ratio of sIg light chains deviated from a designated threshold within the putative CLL cell region. Using this method, we could detect atypical CLL cells at a level of 10-4. We propose this method as an effective MRD assay.


Assuntos
Citometria de Fluxo , Cadeias kappa de Imunoglobulina , Cadeias lambda de Imunoglobulina , Imunofenotipagem , Leucemia Linfocítica Crônica de Células B , Neoplasia Residual , Humanos , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/patologia , Neoplasia Residual/diagnóstico , Imunofenotipagem/métodos , Citometria de Fluxo/métodos , Feminino , Masculino , Cadeias Leves de Imunoglobulina/metabolismo
13.
Clin Lab ; 70(5)2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38747915

RESUMO

BACKGROUND: As a tumor mass, a myeloid sarcoma consists of myeloid blasts and presents at an anatomical site other than the bone marrow. In about one quarter of cases, myeloid sarcoma happens without an underlying acute myeloid leukemia or other myeloid neoplasm, and it may precede or coincide with AML or form acute blastic transformation of MDSs, MPNs, or MDS/MPNs. METHODS: Herein, we described a rare case of acute myeloid leukemia with myelodysplasia-related changes (AML-MRC), with WT1 mutation and high expression of TP53 after isolated myeloid sarcoma of lymph nodes showing a higher proportion of blasts, dysplasia of both megakaryocytes and granulocytes. CONCLUSIONS: The case highlights the importance of a bone marrow examination, including morphology, immunophenotyping, cytogenetic, and molecular examination in all cases to exclude the possibility of myeloid sarcoma, especially the morphological feature of bone marrow dysplasia in the early stage before AML.


Assuntos
Leucemia Mieloide Aguda , Mutação , Síndromes Mielodisplásicas , Sarcoma Mieloide , Humanos , Sarcoma Mieloide/genética , Sarcoma Mieloide/diagnóstico , Sarcoma Mieloide/patologia , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/diagnóstico , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/patologia , Síndromes Mielodisplásicas/diagnóstico , Proteína Supressora de Tumor p53/genética , Proteínas WT1/genética , Masculino , Medula Óssea/patologia , Pessoa de Meia-Idade , Imunofenotipagem
14.
Clin Lab ; 70(5)2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38747916

RESUMO

BACKGROUND: The goal was to improve the clinical cognition of Ph-positive mixed phenotype acute leukemia and avoid misdiagnosis or delayed diagnosis. METHODS: The clinical manifestations and laboratory results (bone marrow cell morphology, multiparameter flow cytometry, and cytogenetics) of a case of Ph-positive mixed phenotype acute leukemia were analyzed, and related literature was reviewed. RESULTS: Blood routine: WBC 386.35 x 109/L, HGB 117.00 g/L, PLT 31 x 109/L; 80% of the original cells can be seen by artificial classification. Morphological examination of bone marrow cells showed that the proliferation of nucleated cells was obviously active, and the original cells accounted for 76%. The size of the original cells was somewhat uniform, most of the cells had less mass, were stained light grayish blue, the cytoplasm particles were not obvious, the nuclei were mostly round or quasi-round, some of them showed distortion and nuclear notch, and the chromatin was coarse. Some of the cells were rich in mass, small azurin granules were seen, the nuclei were regular, most of them were round, the chromatin was fine, the myeloperoxidase and esterase staining were negative, the eosinophils accounted for 2.5%, and the basophils accounted for 0.5%. Flow cytometry immunotyping: Two groups of abnormal cells were seen in the bone marrow. 1. A group included 12.32% of nuclear cells and showed abnormal myeloid primitive cell phenotype. Main expression: CD117, CD34, CD38, HLA-DR, CD33, CD64, CD123, weak expression: CD13, CD19. 2. The other group included 45.61% of the nuclear cells and had a B-lymphoblastic phenotype. Main expression: CD34, CD38, HLA-DR, CD123, CD19, CD10, CD9, cCD79a, TDT, weak expression of CD13, CD22. Mixed phenotype acute leukemia (M/B) immunophenotype was considered. Chromosome: 46,XY,t(9; 22)(q34;q11.2) [20]. BCR-ABL (P210) fusion gene was positive. CONCLUSIONS: Mixed phenotype acute leukemia (MPAL) is a rare type of malignant hematologic disease. Its diagnosis is based on the comprehensive evaluation of bone marrow cell morphology, immunophenotype, molecular and cytogenetic features.


Assuntos
Citometria de Fluxo , Fenótipo , Humanos , Citometria de Fluxo/métodos , Masculino , Imunofenotipagem/métodos , Células da Medula Óssea/patologia , Células da Medula Óssea/metabolismo , Cromossomo Filadélfia , Leucemia Aguda Bifenotípica/diagnóstico , Leucemia Aguda Bifenotípica/genética , Leucemia Aguda Bifenotípica/patologia , Leucemia/diagnóstico , Leucemia/patologia , Leucemia/imunologia , Adulto , Feminino , Pessoa de Meia-Idade
15.
Clin Lab ; 70(5)2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38747919

RESUMO

BACKGROUND: For many years it has been postulated that the immune system controls the progress of multiple myeloma (MM). However, the phenotypes of T cells in MM remain to be elucidated. In this study, we compared the phenotypes of T cells, which were obtained from the peripheral blood, in MM patients with those in healthy donors (HD). The expression of CCR7, CD57, CD28, HLA-DR, CD38, CD45RA, and CD45RO were assessed on T cells from MM patients and HDs using multicolor flow cytometry (MFC). METHODS: For this study, 17 newly diagnosed MM patients were selected, and 20 healthy people were selected as a control group. MFC was used to detect the markers on T cells. RESULTS: We detected significant increases in the expression levels of HLA-DR, CD38, and CD57on CD8+ T cells, significant decreases in the expression levels of CD28 and CD45RA on CD8+ T cells, and a decrease of CD4+ effec-tor T cells in MM patients, compared to the HD group. CONCLUSIONS: Our study shows that the accumulation of peripheral CD8+CD57+T cells, CD8+CD38high T cells, and CD8+HLA-DR+CD38high T cells is reflective of an ongoing antitumor T cell response and a progressive immune dysfunction in MM. During chemotherapy, the recovery of immune function can be monitored by detecting the proportion of activated molecules of T lymphocytes.


Assuntos
ADP-Ribosil Ciclase 1 , Antígenos CD28 , Citometria de Fluxo , Antígenos HLA-DR , Antígenos Comuns de Leucócito , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/imunologia , Antígenos CD28/imunologia , Antígenos CD28/metabolismo , ADP-Ribosil Ciclase 1/metabolismo , Antígenos HLA-DR/imunologia , Antígenos HLA-DR/metabolismo , Antígenos HLA-DR/sangue , Antígenos Comuns de Leucócito/metabolismo , Masculino , Pessoa de Meia-Idade , Feminino , Idoso , Antígenos CD57/metabolismo , Estudos de Casos e Controles , Imunofenotipagem/métodos , Linfócitos T/imunologia , Linfócitos T/metabolismo , Adulto , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Glicoproteínas de Membrana/imunologia
16.
Autoimmunity ; 57(1): 2356089, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38770919

RESUMO

Autoimmune hepatitis (AIH) is a chronic, inflammatory liver disease of unknown aetiology which requires lifelong immunosuppression. Most therapeutic and outcome studies of AIH have been conducted predominantly in Caucasian (European Ancestry, EA) cohorts, with the exclusion of African American (AA) patients due to inadequate sample size. It is known that AA patients have a severe phenotype of autoimmune diseases and demonstrate a poor response to conventional medical therapy. Understanding cellular and molecular pathways which determine AIH severity and progression in AA patients is likely to lead to the discovery of novel, personalised and better tolerated therapies. The aim of the study is to determine the distinct effector B cell phenotypes which contribute to disease severity and progression of AIH in AA children as compared to their EA cohorts. PBMCs were isolated from blood samples collected from patients visiting Children's Healthcare of Atlanta (CHOA) and were grouped into AA, (n = 12), EA, (n = 11) and controls (n = 12) and were processed for flow cytometry. Markers of B cell development, maturation and activation were assessed namely CD19, CD21, IgD, CD27, CD38, CD11c, CD24, CD138. AA children with AIH demonstrated an expansion of CD19 + ve, Activated Naïve (aN), (CD19+ IgD-/CD27- Double Negative (DN2) ([CD19+/IgD-/CD27++CD38++) cells. Plasmablasts were significantly higher along with Signalling Lymphocytic activation molecule F7 (SLAMF7). Unswitched memory [CD19+] IgD+CD27+ (USM) B cells were significantly contracted in AA patients with AIH. B cell phenotyping reveals a distinct profile in AA AIH patients with a major skewing towards the expansion of effector pathways which have been previously characterised in severe SLE in AA patients. These results suggest that the quantification and therapeutic target of B cell pathway could contribute substantially to the clinical approach to AIH especially in the AA population.


Assuntos
Linfócitos B , Hepatite Autoimune , Imunoglobulina D , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral , Humanos , Hepatite Autoimune/imunologia , Hepatite Autoimune/sangue , Hepatite Autoimune/patologia , Hepatite Autoimune/diagnóstico , Imunoglobulina D/imunologia , Imunoglobulina D/metabolismo , Criança , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismo , Masculino , Feminino , Adolescente , Linfócitos B/imunologia , Linfócitos B/metabolismo , Pré-Escolar , Imunofenotipagem , Subpopulações de Linfócitos B/imunologia , Subpopulações de Linfócitos B/metabolismo , Idade de Início , Biomarcadores
17.
Medicina (Kaunas) ; 60(5)2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38792990

RESUMO

Spontaneous remissions (SRs) in blastic plasmacytoid dendritic cell neoplasms (BPDCNs) are infrequent, poorly documented, and transient. We report a 40-year-old man presenting with bycitopenia and soft tissue infection. The bone marrow exhibited 3% abnormal cells. Immunophenotyping of these cells revealed the antigens CD45+ (dim), CD34+, CD117+, CD123+ (bright), HLA-DR+ (bimodal), CD56+ (bright), CD33+, CD13+, CD2+, and CD22+ (dim) and the partial expression of the CD10+, CD36+, and CD7+ antigens. All other myeloid, monocytic, and lymphoid antigens were negative. Genetic studies showed a complex karyotype and mutations in the TP53R337C and KRASG12D genes. On hospital admission, the patient showed a subcutaneous nodule on the right hand and left lower limb. Flow cytometry multiparameter (FCM) analysis showed the presence of 29% abnormal cells with the previously described immunophenotype. The patient was diagnosed with BPDCN. The patient was treated with broad-spectrum antibiotics for soft tissue infection, which delayed therapy for BPDCN. No steroids or chemotherapeutic or hypomethylating agents were administered. His blood cell counts improved and skin lesions disappeared, until the patient relapsed five months after achieving spontaneous remission. About 60% of abnormal cells were identified. No changes in immunophenotype or the results of genetic studies were observed. The patient underwent a HyperCVAD chemotherapy regimen for six cycles. Consolidation therapy was performed via allogeneic bone marrow transplantation with an HLA-unrelated donor. One year after the bone marrow transplant, the patient died due to the progression of his underlying disease, coinciding with a respiratory infection caused by SARS-CoV-2. In the available literature, SRs are often linked to infections or other stimulators of the immune system, suggesting that powerful immune activation could play a role in controlling the leukemic clone. Nevertheless, the underlying mechanism of this phenomenon is not clearly understood. We hypothesize that the immune system would force the leukemic stem cell (LSC) to undergo a state of quiescence. This loss of replication causes the LSC progeny to die off, resulting in the SR of BPDCN.


Assuntos
Células Dendríticas , Humanos , Masculino , Adulto , Remissão Espontânea , Imunofenotipagem , Neoplasias Hematológicas
18.
Viruses ; 16(5)2024 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-38793691

RESUMO

In patients with COVID-19, broad panels of immune checkpoint molecules (ICPMs) and the purinergic signaling have not been studied in parallel. We aimed to perform in-depth immunophenotyping of major cell subsets present in human peripheral blood of COVID-19 patients and controls using PD1, TIM3, LAG3, TIGIT, and CD200R, as well as CD39, as markers for the purinergic signaling pathway. We studied 76 COVID-19 patients and 12 healthy controls using peripheral blood mononuclear cells on flow cytometry. Univariable and multivariable statistics were performed. All ICPMs studied were significantly overexpressed on different cell subsets of COVID-19 patients when compared with healthy controls. Elevated lactate dehydrogenase; C-reactive protein; age; and high expression of CD45+, CD39+CD45+, TIM3+CD39+CD4+CD45+, and TIM3+CD39+CD8+CD3+CD4+ cells were significantly associated with severe COVID-19. On multivariable analysis, however, only high expression of CD39+CD45+ (OR 51.4, 95% CI 1.5 to 1763) and TIM3+CD39+CD4+CD3+CD45+ (OR 22.6, 95% CI 1.8 to 277) cells was an independent predictor for severe COVID-19. In conclusion, numerous ICPMs are overexpressed in COVID-19 patients when compared with healthy controls, suggesting a pathophysiological role of these molecules in SARS-CoV-2 infection. However, only TIM3 in co-expression with CD39 remained as a significant independent prognostic ICPM on multivariable analysis. The flow cytometric evaluation of TIM3+CD39+CD4+CD3+CD45+, as well as CD39+CD45+, is a powerful tool for the prognostication of COVID-19 patients on hospital admission.


Assuntos
Apirase , COVID-19 , SARS-CoV-2 , Humanos , COVID-19/mortalidade , COVID-19/imunologia , COVID-19/diagnóstico , COVID-19/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Idoso , Estudos Prospectivos , SARS-CoV-2/imunologia , Adulto , Índice de Gravidade de Doença , Proteínas de Checkpoint Imunológico/genética , Proteínas de Checkpoint Imunológico/metabolismo , Antígenos CD/sangue , Leucócitos Mononucleares/imunologia , Imunofenotipagem , Citometria de Fluxo , Idoso de 80 Anos ou mais
19.
Front Immunol ; 15: 1321126, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38711501

RESUMO

Introduction: γδ T cells recognize and exert cytotoxicity against tumor cells. They are also considered potential immune cells for immunotherapy. Our previous study revealed that the altered expression of immune checkpoint T-cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) on γδ T cells may result in immunosuppression and is possibly associated with a poor overall survival in acute myeloid leukemia (AML). However, whether γδ T-cell memory subsets are predominantly involved and whether they have a relationship with clinical outcomes in patients with AML under the age of 65 remain unclear. Methods: In this study, we developed a multicolor flow cytometry-based assay to monitor the frequency and distribution of γδ T-cell subsets, including central memory γδ T cells (TCM γδ), effector memory γδ T cells (TEM γδ), and TEM expressing CD45RA (TEMRA γδ), in peripheral blood from 30 young (≤65 years old) patients with newly diagnosed non-acute promyelocytic leukemia (also known as M3) AML (AMLy-DN), 14 young patients with AML in complete remission (AMLy-CR), and 30 healthy individuals (HIs). Results: Compared with HIs, patients with AMLy-DN exhibited a significantly higher differentiation of γδ T cells, which was characterized by decreased TCM γδ cells and increased TEMRA γδ cells. A generally higher TIGIT expression was observed in γδ T cells and relative subsets in patients with AMLy-DN, which was partially recovered in patients with AMLy-CR. Furthermore, 17 paired bone marrow from patients with AMLy-DN contained higher percentages of γδ and TIGIT+ γδ T cells and a lower percentage of TCM γδ T cells. Multivariate logistic regression analyses revealed the association of high percentage of TIGIT+ TCM γδ T cells with an increased risk of poor induction chemotherapy response. Conclusions: In this study, we investigated the distribution of γδ T cells and their memory subsets in patients with non-M3 AML and suggested TIGIT+ TCM γδ T cells as potential predictive markers of induction chemotherapy response.


Assuntos
Receptores de Antígenos de Linfócitos T gama-delta , Receptores Imunológicos , Humanos , Receptores Imunológicos/metabolismo , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Prognóstico , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Adulto Jovem , Idoso , Células T de Memória/imunologia , Células T de Memória/metabolismo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Leucemia Mieloide Aguda/imunologia , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/diagnóstico , Memória Imunológica , Leucemia Promielocítica Aguda/imunologia , Leucemia Promielocítica Aguda/diagnóstico , Leucemia Promielocítica Aguda/mortalidade , Imunofenotipagem
20.
Cell Mol Biol (Noisy-le-grand) ; 70(5): 1-9, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38814241

RESUMO

Non-Hodgkin lymphoma (NHL) is a lymphoproliferative disorder derived from either B or T lymphocytes. Among NHL, activated B-cell-like (ABC) diffuse large B-cell lymphoma (DLBCL) and T cell non-Hodgkin lymphomas (T-NHL) are poor prognosis and aggressive subtypes. Macrophages are professional phagocytic cells and dendritic cells (DCs) are professional antigen-presenting cells in immune system. Doxorubicin (Dox) and Etoposide (ET) are the most effective anti-cancer drugs. A20 and CYLD are negative regulators of NF-κB-dependent functions in many cell types. Little is known about the roles of A20 and CYLD in regulating functions of DCs and macrophages from NHL. The present study, therefore, explored whether A20/CYLD expression contributes to functions of DCs and macrophages from NHL. To this end, blood samples of seventy-nine patients with ABC DLBCL and T-NHL were examined. Gene expression profile was determined by quantitative RT-PCR and immunophenotype, cell apoptosis and phagocytosis by flow cytometry. As a result, immunophenotypic analysis showed that the numbers of CD13+CD117-, CD56+CD40+ and CD23+CD40+ expressing cells were significantly elevated in ABC DLBCL cases compared to healthy individuals and T-NHL patients. Interestingly, upon treatment of Dox and ET, the phagocytosis of lymphoma cells was significantly reduced by CD11c+CD123- DCs and the percentage of CD56+ mature DCs was significantly enhanced in ABC DLBCL patients only in the presence of A20 siRNA, but not CYLD siRNA. In conclusion, ABC DLBCL patients with low A20 expression were defective in elimination of lymphoma cells by DCs and linked to killer DC expansion in circulation.


Assuntos
Células Dendríticas , Linfoma Difuso de Grandes Células B , Fagocitose , Proteína 3 Induzida por Fator de Necrose Tumoral alfa , Humanos , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Fagocitose/efeitos dos fármacos , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/metabolismo , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/genética , Feminino , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/imunologia , Pessoa de Meia-Idade , Masculino , Linfoma não Hodgkin/patologia , Linfoma não Hodgkin/imunologia , Apoptose/efeitos dos fármacos , Idoso , Adulto , Macrófagos/metabolismo , Macrófagos/imunologia , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Linfócitos B/imunologia , Linfócitos B/metabolismo , Imunofenotipagem
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