RESUMEN
T-lymphoblastic leukemia/lymphoma (T-ALL/LBL) is a rare acute leukemia that expresses cytoplasmic CD3 (cCD3) and frequently lacks surface CD3. Given that routine flow cytometric testing for cCD3 may not be feasible and cCD3 interpretation may be difficult, we investigate if surface CD2 and/or CD7 expression on blasts can be used by flow cytometry to screen for T-lineage acute leukemia. We retrospectively reviewed flow cytometric data from 233 acute leukemias (36 T-ALL/LBL, 8 mixed-phenotype acute leukemia T/myeloid, 80 acute myeloid leukemia, 97 B-ALL/LBL, 8 mixed-phenotype acute leukemia B/myeloid, and 4 acute undifferentiated leukemia cases). Uniform expression (≥75% of blasts) of CD2 and/or CD7 was seen in all 44 cCD3-positive cases but in only 11% (20/189) of cCD3-negative acute leukemias, thus demonstrating 100% sensitivity and 89% specificity in the identification of cCD3-positive (T-lineage) acute leukemia. To avoid selection bias, we prospectively studied 232 consecutive acute leukemias for which cCD3, CD2, and CD7 were automatically performed in all cases. Similar to the retrospective study, uniform expression of CD2 and/or CD7 on blasts showed 100% sensitivity and 88% specificity in the screening for cCD3-positive (T-lineage) acute leukemia. Therefore, acute leukemias with uniform expression of CD2 and/or CD7 warrant further testing for cCD3 to evaluate for T-lineage acute leukemia. Blasts that lack both uniform CD2 and CD7 expression do not require additional cCD3 testing. We propose that CD2 and CD7 could be utilized in a limited antibody flow cytometry panel as a sensitive, robust, and cost-effective way to screen for T-lineage acute leukemia.
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Antígenos CD7/análisis , Biomarcadores de Tumor/análisis , Antígenos CD2/análisis , Linaje de la Célula , Citometría de Flujo , Inmunofenotipificación , Leucemia-Linfoma Linfoblástico de Células T Precursoras/inmunología , Linfocitos T/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Complejo CD3/análisis , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Fenotipo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patología , Valor Predictivo de las Pruebas , Estudios Prospectivos , Reproducibilidad de los Resultados , Estudios Retrospectivos , Adulto JovenRESUMEN
Protein-protein interactions (PPI) by homo-, hetero- or oligo-merization in the cellular environment regulate cellular processes. PPI can be inhibited by antibodies, small molecules or peptides, and this inhibition has therapeutic value. A recently developed method, the proximity ligation assay (PLA), provides detection of PPI in the cellular environment. However, most applications using this assay are for proteins expressed in the same cell. We employ PLA for the first time to study PPI of cell surface proteins on two different cells. Inhibition of PPI using a peptide inhibitor is also quantified using this assay; PLA is used to detect PPI of CD2 and CD58 between Jurkat cells (T cells) and human fibroblast-like synoviocyte-rheumatoid arthritis cells that are important in the immune response in the autoimmune disease rheumatoid arthritis. This assay provides direct evidence of inhibition of PPI of two proteins on different cell surfaces.
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Biotecnología/métodos , Antígenos de Histocompatibilidad Clase II/análisis , Proteínas de la Membrana/química , Proteínas/química , Antígenos CD2/análisis , Antígenos CD2/metabolismo , Antígenos CD58/análisis , Antígenos CD58/metabolismo , Células Cultivadas , Citometría de Flujo , Antígenos de Histocompatibilidad Clase II/metabolismo , Humanos , Células Jurkat , Proteínas de la Membrana/análisis , Modelos Moleculares , Unión Proteica , SinoviocitosRESUMEN
Cancer immunotherapy has proven high efficacy in treating diverse cancer entities by immune checkpoint modulation and adoptive T-cell transfer. However, patterns of treatment response differ substantially from conventional therapies, and reliable surrogate markers are missing for early detection of responders versus non-responders. Current imaging techniques using 18F-fluorodeoxyglucose-positron-emmission-tomograpy (18F-FDG-PET) cannot discriminate, at early treatment times, between tumor progression and inflammation. Therefore, direct imaging of T cells at the tumor site represents a highly attractive tool to evaluate effective tumor rejection or evasion. Moreover, such markers may be suitable for theranostic imaging. Methods: We mainly investigated the potential of two novel pan T-cell markers, CD2 and CD7, for T-cell tracking by immuno-PET imaging. Respective antibody- and F(ab´)2 fragment-based tracers were produced and characterized, focusing on functional in vitro and in vivo T-cell analyses to exclude any impact of T-cell targeting on cell survival and antitumor efficacy. Results: T cells incubated with anti-CD2 and anti-CD7 F(ab´)2 showed no major modulation of functionality in vitro, and PET imaging provided a distinct and strong signal at the tumor site using the respective zirconium-89-labeled radiotracers. However, while T-cell tracking by anti-CD7 F(ab´)2 had no long-term impact on T-cell functionality in vivo, anti-CD2 F(ab´)2 caused severe T-cell depletion and failure of tumor rejection. Conclusion: This study stresses the importance of extended functional T-cell assays for T-cell tracer development in cancer immunotherapy imaging and proposes CD7 as a highly suitable target for T-cell immuno-PET imaging.
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Traslado Adoptivo/métodos , Antígenos CD7/análisis , Inmunoterapia/métodos , Imagen Molecular/métodos , Neoplasias/terapia , Linfocitos T/química , Linfocitos T/inmunología , Animales , Antígenos CD2/análisis , Línea Celular Tumoral , Modelos Animales de Enfermedad , Xenoinjertos , Humanos , Fragmentos Fab de Inmunoglobulinas/administración & dosificación , Ratones , Trasplante de Neoplasias , Tomografía de Emisión de Positrones/métodos , Trazadores Radiactivos , Radiofármacos/administración & dosificaciónRESUMEN
Systemic mastocytosis (SM) with associated clonal nonmast cell lineage disease is seen in up to 20% cases of SM. SM is uncommon in the pediatric population. T (8; 21) (q22; q22) is a good prognostic factor in acute myeloid leukemia (AML). However, the presence of SM confers poor prognosis in t (8; 21) (q22; q22) associated AML. We report the case of a child with t (8; 21) (q22; q22) associated AML with SM and her minimal residual disease status over the course of her treatment. In our case, the abnormal mast cells, showing co-expression of CD25 and CD2, persisted even after the marrow showed no evidence of residual AML.
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Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/diagnóstico , Mastocitosis Sistémica/complicaciones , Mastocitosis Sistémica/diagnóstico , Translocación Genética , Médula Ósea/patología , Antígenos CD2/análisis , Niño , Femenino , Humanos , Subunidad alfa del Receptor de Interleucina-2/análisis , Mastocitos/químicaAsunto(s)
Rubor/etiología , Mastocitosis Sistémica/complicaciones , Mastocitosis Sistémica/genética , Proteínas Proto-Oncogénicas c-kit/genética , Adulto , Anciano , Antígenos CD2/análisis , Femenino , Humanos , Subunidad alfa del Receptor de Interleucina-2 , Masculino , Mastocitos/química , Persona de Mediana Edad , Mutación , Estudios Prospectivos , Tasa de SupervivenciaRESUMEN
UNLABELLED: Molecular factors driving immune-mediated inflammation in the liver are incompletely understood. The transcription factor, cyclic adenosine monophosphate-responsive element modulator alpha (CREMα) can endorse differentiation of T lymphocytes toward T-helper (Th)17 cells, thereby promoting autoimmunity in systemic lupus erythematosus or lung inflammation. To investigate the role of CREMα in liver disease, we subjected transgenic (Tg) mice overexpressing CREMα under control of the CD2 promoter (cremtg mice), which restrains expression mainly to lymphocytes (T, natural killer [NK], and NKT cells), to acute and chronic liver injury models. Already in steady state, Tg CREMα overexpression broadly reduced hepatic immune cell numbers by decreasing their viability, but did not affect immune cell migration or the fibrogenic response to chronic liver injury. Strikingly, cremtg mice developed more severe immune-mediated hepatitis with a higher mortality rate, compared to wild-type (wt) mice, upon concanavalin A (ConA) administration. Unlike in T cells from spleen, CREMα overexpression did not induce a predominant Th17 response in intrahepatic T cells, given that hepatic cremtg CD4+ T cells expressed less interleukin (IL)-17 than wt T cells. Reconstitution of Rag1-/- mice with Crem-/- T cells did not ameliorate ConA hepatitis. Overexpression of CREMα did not influence NK and NKT-cell effector functions either. Interestingly, a subset of monocytic myeloid-derived suppressor cells (MDSCs) also expressed CD2 and CREMα. Cremtg MDSCs isolated from liver expressed reduced inducible nitric oxide synthase and arginase 1 and displayed a reduced T-cell suppressive activity. The adoptive transfer of wt MDSCs was capable of reducing the fulminant immune-mediated liver damage in cremtg mice to wt level. CONCLUSION: These results suggest compartmental differences of T cell activation pathways between liver and other organs in autoimmunity and define a functional role of CREMα in hepatic monocytic MDSCs for the pathogenesis of immune-mediated liver disease.
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Modulador del Elemento de Respuesta al AMP Cíclico/fisiología , Hepatitis Autoinmune/etiología , Hígado/inmunología , Células Mieloides/fisiología , Traslado Adoptivo , Animales , Antígenos CD2/análisis , Diferenciación Celular , Concanavalina A , Cirrosis Hepática Experimental/etiología , Ratones , Ratones Transgénicos , Linfocitos T/inmunología , Células Th17/fisiologíaRESUMEN
This work reports an efficient, specific, and sensitive immunoassay protocol for detection of tumor cells by using inductively coupled plasma mass spectrometry (ICP-MS) with two probes. Magnetic nanobeads modified with anti-CD3 were used as capture probes for efficient and fast magnetic separation of Jurkat T cells from a mixture of cells, and gold nanoparticles (Au NPs) conjugated with anti-CD2 were used as detection probes for ICP-MS measurement. The capture and detection probes target the Jurkat T cells with high affinity and specificity, while they do not target other CD2/CD3-negative cells such as 97L cells and A549 cells. On the basis of these results, we proposed a new immunoassay for specific detection of Jurkat T cells. The conditions for this immunoassay were carefully optimized, including the incubation time and temperature, the concentration of the labeling probe, and the elution conditions. Under the optimized conditions, the linear range of 300-30,000 and the limit of detection of 86 Jurkat T cells were obtained, and the relative standard deviation for seven replicate detection of Jurkat T cells was 5.2% (3000 Jurkat T cells). This method has numerous advantages, including ease of preparation, low sample consumption, and high sensitivity and selectivity. Importantly, the methodology could be extended to the simultaneous detection of other cells based on their cellular biomarkers.
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Anticuerpos Inmovilizados , Oro/química , Separación Inmunomagnética/métodos , Nanopartículas del Metal/química , Neoplasias/diagnóstico , Anticuerpos Inmovilizados/química , Antígenos CD2/análisis , Complejo CD3/análisis , Línea Celular Tumoral , Separación Celular/métodos , Humanos , Inmunoensayo/métodos , Células Jurkat , Espectrometría de Masas/métodosRESUMEN
Patients with resected stage II-III cutaneous melanomas remain at high risk for metastasis and death. Biomarker development has been limited by the challenge of isolating high-quality RNA for transcriptome-wide profiling from formalin-fixed and paraffin-embedded (FFPE) primary tumor specimens. Using NanoString technology, RNA from 40 stage II-III FFPE primary melanomas was analyzed and a 53-immune-gene panel predictive of non-progression (area under the curve (AUC)=0.920) was defined. The signature predicted disease-specific survival (DSS P<0.001) and recurrence-free survival (RFS P<0.001). CD2, the most differentially expressed gene in the training set, also predicted non-progression (P<0.001). Using publicly available microarray data from 46 primary human melanomas (GSE15605), a coexpression module enriched for the 53-gene panel was then identified using unbiased methods. A Bayesian network of signaling pathways based on this data identified driver genes. Finally, the proposed 53-gene panel was confirmed in an independent test population of 48 patients (AUC=0.787). The gene signature was an independent predictor of non-progression (P<0.001), RFS (P<0.001), and DSS (P=0.024) in the test population. The identified driver genes are potential therapeutic targets, and the 53-gene panel should be tested for clinical application using a larger data set annotated on the basis of prospectively gathered data.
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Redes Reguladoras de Genes , Melanoma/inmunología , Teorema de Bayes , Antígenos CD2/análisis , Genes p53 , Humanos , Melanoma/genética , Melanoma/mortalidad , Melanoma/patología , Estadificación de NeoplasiasRESUMEN
Acute myeloid leukemia with inv3(q21q26.2)/t(3,3)(q21;q26.2) is a subtype of acute myeloid leukemia associated with significant dysmyelopoiesis and a poor prognosis. In more than a half of the cases, there is also monosomy 7. We present 2 young male patients with de novo acute myeloid leukemia with inversion 3 and monosomy 7 who had significant morphologic and immunophenotypical similarities. Both patients had circulating subsets of blasts with unusual intracytoplasmic basophilic granules and prominent bone marrow dysmegakaryopoiesis. The leukemic myeloid blasts were negative for myeloperoxidase and had aberrant coexpression of CD2 and CD31. Despite their morphologic and immunophenotypical similarities, only 1 of the patients achieved remission and remained free of disease 24 months after bone marrow transplant. The younger patient, who had also increased hemoglobin F and an associated FLT3 D835 variant, had an acute myeloid leukemia refractory to chemotherapy and died 4 months after his diagnosis.
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Antígenos CD2/biosíntesis , Deleción Cromosómica , Cromosomas Humanos Par 3 , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patología , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/biosíntesis , Adulto , Biomarcadores de Tumor/análisis , Antígenos CD2/análisis , Cromosomas Humanos Par 3/genética , Cromosomas Humanos Par 7 , Humanos , Masculino , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/análisisRESUMEN
Resting memory CD4(+) T cells are the largest reservoir of persistent infection in HIV-1-positive subjects. They harbor dormant, stably integrated virus despite suppressive antiretroviral therapy, posing an obstacle to a cure. Surface markers that identify latently infected cells remain unknown. Microarray analyses comparing resting latently infected and uninfected CD4(+) T cells generated in vitro showed profound differences in the expression of gene programs related to transcriptional and posttranscriptional regulation, cell proliferation, survival, cycle progression, and basic metabolism, suggesting that multiple biochemical and metabolic blocks contribute to preventing viral production in latently infected cells. We identified 33 transcripts encoding cell surface markers that are differentially expressed between latently infected and uninfected cells. Quantitative reverse transcriptase PCR (RT-QPCR) and flow cytometry analyses confirmed that the surface marker CD2 was expressed at higher levels on latently infected cells. To validate this result in vivo, we sorted resting memory CD4(+) T cells expressing high and low surface levels of CD2 from six HIV-1-infected subjects successfully treated with antiretroviral drugs for at least 3 years. Resting memory CD4(+) CD2(high) T cells from all subjects harbored higher HIV-1 DNA copy numbers than all other CD4(+) T cell subsets. Moreover, after ex vivo viral reactivation, robust viral RNA production was detected only from resting memory CD4(+) CD2(high) T cells but not from other cell subsets. Altogether, these results show that a high CD2 expression level is a hallmark of latently infected resting memory CD4(+) T cells in vivo.
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Antígenos CD2/análisis , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/virología , Infecciones por VIH/inmunología , VIH-1/fisiología , Memoria Inmunológica , Latencia del Virus , Linfocitos T CD4-Positivos/química , ADN Viral/análisis , ADN Viral/genética , Citometría de Flujo , Perfilación de la Expresión Génica , VIH-1/genética , Humanos , Provirus/genética , ARN Viral/biosíntesis , Reacción en Cadena en Tiempo Real de la Polimerasa , Activación ViralRESUMEN
Membrane nanotubes are thin membranous projections that physically connect two cells. While nanotubes have been studied in human natural killer (NK) cells and are implicated in aiding NK cell cytotoxic function, requirements for their formation to susceptible target cells remain incompletely understood. Here we demonstrate that the CD2-CD58/48 receptor-ligand interaction promotes and is required for nanotube formation in human NK cells. In the CD2(-) NK cell line YTS, a stable CD2 expression variant enabled effective nanotube formation, and was associated with better cytotoxic function. Importantly, only interactions between an NK cell and a susceptible target cell were associated with multiple nanotubes and the number of nanotubes was inversely correlated with their length. Quantitative live cell fluorescence microscopy of CD2 nanotubes revealed time-dependent enrichment and localization of CD2 to the nanotube tip, and blocking CD2 receptor-ligand interactions prevented nanotube formation. Increased nanotube formation was not simply a feature of receptor-ligand pairing, as a KIR-MHC interaction in the same cell line system failed to promote nanotube formation. Additionally, blocking LFA-1-ICAM and 2B4-CD48 receptor-ligand interactions failed to inhibit nanotube formation. Thus only specific receptor-ligand pairs promote nanotubes. CD2 also promoted nanotube formation in ex vivo NK cells suggesting that CD2 plays a crucial role in the generation of nanotubes between an NK cell and its target.
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Antígenos CD2/inmunología , Antígenos CD58/inmunología , Membrana Celular/inmunología , Membrana Celular/ultraestructura , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/ultraestructura , Antígenos CD2/análisis , Antígenos CD58/análisis , Línea Celular , HumanosRESUMEN
Systemic mastocytosis with associated clonal hematological nonmast cell lineage disease (SM-AHNMD) is a subtype of mastocytosis associated commonly with myeloid neoplasms, Non-Hodgkin's lymphoma, or other hematological neoplasms. In these conditions, mastocytosis needs to be differentiated from mast cell hyperplasia or mast cell activation states. Neoplastic nature of mastocytosis is proved either by morphology, aberrant immunophenotype, or detection of point mutation at codon-816 of c-kit gene. This is a rare entity, even more so in pediatric population. Herein, we report a case of 14-year-old girl with SM associated with acute myeloid leukemia with maturation with t(8;21). Multifocal dense infiltrate of spindle-shaped mast cells on bone marrow aspirate and biopsy with coexpression of CD2 and CD25 by flow cytometric analysis proved the SM component at the time of diagnosis and persistence at post induction status also.
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Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/diagnóstico , Mastocitosis Sistémica/complicaciones , Mastocitosis Sistémica/diagnóstico , Translocación Genética , Adolescente , Médula Ósea/patología , Antígenos CD2/análisis , Femenino , Citometría de Flujo , Humanos , Subunidad alfa del Receptor de Interleucina-2/análisis , MicroscopíaRESUMEN
Radiotherapy of intrathoracic and chest wall tumors may lead to exposure of the heart to ionizing radiation, resulting in radiation-induced heart diseases (RIHD). The main manifestations of RIHD become apparent many years after treatment and include cardiomyopathy and accelerated atherosclerosis. This study examines the role of the kallikrein-kinin system (KKS) in RIHD by investigating the cardiac radiation response in a kininogen-deficient Brown Norway Katholiek (BN/Ka) rat model. BN/Ka rats and wild-type Brown Norway (BN) rats were exposed to local heart irradiation with a single dose of 18 Gy or 24 Gy and were observed for 3 to 6 months. Examinations included in vivo and ex vivo cardiac function, histopathology, gene and protein expression measurements, and mitochondrial swelling assays. Upon local heart irradiation, changes in in vivo cardiac function were significantly less in BN/Ka rats. For instance, a single dose of 24 Gy caused a 35% increase in fractional shortening in BN rats compared with a 16% increase in BN/Ka rats. BN rats, but not BN/Ka rats, showed a 56% reduction in cardiac numbers of CD2-positive cells, and a 57% increase in CD68-positive cells, together with a 52% increase in phosphorylation of extracellular signal-regulated kinase 1/2 (Erk1/2). Local heart irradiation had similar effects on histopathology, mitochondrial changes, and left ventricular mRNA levels of NADPH oxidases in the two genotypes. These results suggest that the KKS plays a role in the effects of radiation on cardiac function and recruitment of inflammatory cells. The KKS may have these effects at least in part by altering Erk1/2 signaling.
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Corazón/fisiopatología , Sistema Calicreína-Quinina , Quininógenos/deficiencia , Miocarditis/metabolismo , Miocardio/metabolismo , Animales , Antígenos CD/análisis , Antígenos de Diferenciación Mielomonocítica/análisis , Western Blotting , Antígenos CD2/análisis , Expresión Génica/efectos de la radiación , Corazón/efectos de la radiación , Inmunohistoquímica , Técnicas In Vitro , Quininógenos/genética , Sistema de Señalización de MAP Quinasas/efectos de la radiación , Dilatación Mitocondrial/efectos de la radiación , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Miocarditis/etiología , Miocarditis/genética , Miocardio/patología , NADPH Oxidasas/genética , Fosforilación/efectos de la radiación , Traumatismos Experimentales por Radiación/complicaciones , Ratas , Ratas Endogámicas BN , Receptor de Bradiquinina B2/genética , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Aberrant expression of CD2 and/or CD25 by bone marrow, peripheral blood or other extracutaneous tissue mast cells is currently used as a minor World Health Organization diagnostic criterion for systemic mastocytosis. However, the diagnostic utility of CD2 versus CD25 expression by mast cells has not been prospectively evaluated in a large series of systemic mastocytosis. Here we evaluate the sensitivity and specificity of CD2 versus CD25 expression in the diagnosis of systemic mastocytosis. Mast cells from a total of 886 bone marrow and 153 other non-bone marrow extracutaneous tissue samples were analysed by multiparameter flow cytometry following the guidelines of the Spanish Network on Mastocytosis at two different laboratories. The 'CD25+ and/or CD2+ bone marrow mast cells' World Health Organization criterion showed an overall sensitivity of 100% with 99.0% specificity for the diagnosis of systemic mastocytosis whereas CD25 expression alone presented a similar sensitivity (100%) with a slightly higher specificity (99.2%). Inclusion of CD2 did not improve the sensitivity of the test and it decreased its specificity. In tissues other than bone marrow, the mast cell phenotypic criterion revealed to be less sensitive. In summary, CD2 expression does not contribute to improve the diagnosis of systemic mastocytosis when compared with aberrant CD25 expression alone, which supports the need to update and replace the minor World Health Organization 'CD25+ and/or CD2+' mast cell phenotypic diagnostic criterion by a major criterion based exclusively on CD25 expression.
Asunto(s)
Antígenos CD2/análisis , Inmunofenotipificación , Subunidad alfa del Receptor de Interleucina-2/análisis , Mastocitos/inmunología , Mastocitosis Sistémica/diagnóstico , Organización Mundial de la Salud , Biomarcadores/análisis , Examen de la Médula Ósea , Distribución de Chi-Cuadrado , Citometría de Flujo , Adhesión a Directriz , Humanos , Inmunofenotipificación/métodos , Inmunofenotipificación/normas , Mastocitosis Sistémica/inmunología , Variaciones Dependientes del Observador , Fenotipo , Guías de Práctica Clínica como Asunto , Valor Predictivo de las Pruebas , Pronóstico , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y Especificidad , EspañaRESUMEN
CONTEXT: Angiofollicular lymph node hyperplasia or Castleman's disease is a rare clinical condition. Knowledge about etiology and physiopathology; and treatment management as well are yet to be defined. Unicentric presentation of this disease affecting single lymph nodes in the mediastinum seems to be the most common presentation. Castleman's disease localized in the pancreas topographic area that mimics a pancreatic neoplasm is an even more uncommon event, with available published data of less than 15 cases until now. CASE REPORT: We present a 64-year-old male patient with a six-month past history of asthenia, adynamia, and lack of general clinical conditions. Imaging studies showed a nodular hypoechoic mass in the pancreatic head. Enucleation of the lesion was performed. Histopathological study revealed unicentric form of Castleman's Disease. CONCLUSIONS: Castleman's disease mimetizing pancreatic tumor is uncommon and it also curses with a difficult preoperative diagnosis. Surgery seems to be the best therapeutic alternative for this disease.
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Enfermedad de Castleman/diagnóstico , Páncreas/patología , Neoplasias Pancreáticas/diagnóstico , Antígenos CD34/análisis , Antígenos CD2/análisis , Enfermedad de Castleman/metabolismo , Diagnóstico Diferencial , Humanos , Inmunohistoquímica , Antígenos Comunes de Leucocito/análisis , Masculino , Persona de Mediana Edad , Páncreas/química , Neoplasias Pancreáticas/metabolismo , Tomografía Computarizada por Rayos XRESUMEN
Mastocytosis can sometimes resemble other skin conditions, especially pigmented ones, not only clinically but also dermatoscopically. We report the case of a woman with the diagnosis of cutaneous mastocytosis mimicking multiple melanocytic nevi. Melanocytic stimulation can be induced by high levels of stem cell factor. The progressive increase in the number of pigmented lesions in a patient should lead us to perform a biopsy to search for mastocytosis.
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Dermoscopía , Mastocitosis Cutánea/diagnóstico , Nevo Pigmentado/diagnóstico , Adulto , Biopsia , Médula Ósea/patología , Antígenos CD2/análisis , Diagnóstico Diferencial , Femenino , Humanos , Subunidad alfa del Receptor de Interleucina-2/análisis , Mastocitos/química , Mastocitos/patología , Mastocitosis Cutánea/genética , Mastocitosis Cutánea/patología , Mutación , Proteínas Proto-Oncogénicas c-kit/genética , Factor de Células Madre/fisiologíaRESUMEN
Mastocytosis is a term used to designate a heterogeneous group of disorders characterized by an abnormal proliferation and accumulation of mast cells (MCs) in one or multiple tissues including skin, bone marrow (BM), liver, spleen, and lymph nodes, among others. Recent advances in our understanding of mast cell biology and disease resulted in the identification of important differences in the expression of mast cell surface antigens between normal and neoplastic mast cells. Most notably, detection of aberrant expression of CD25 and CD2 on the surface of neoplastic mast cells but not on their normal counterparts lead to the inclusion of this immunophenotypic abnormality in the World Health Organization diagnostic criteria for systemic mastocytosis. Aberrant mast cell surface marker expression can be detected in the bone marrow aspirate by flow cytometry, even in patients lacking histopathologically detectable aggregates of mast cells in bone marrow biopsy sections. These aberrant immunophenotypic features are of great relevance for the assessment of tissue involvement in mastocytosis with consequences in the diagnosis, classification, and follow-up of the disease and in its differential diagnosis with other entities. In this chapter, we provide the reader with information for the objective and reproducible identification of pathologic MCs by using quantitative multiparametric flow cytometry, for their phenotypic characterization, and the criteria currently used for correct interpretation of the immunophenotypic results obtained.
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Médula Ósea/patología , Antígenos CD2/análisis , Citometría de Flujo/métodos , Inmunofenotipificación/métodos , Subunidad alfa del Receptor de Interleucina-2/análisis , Mastocitos/patología , Mastocitosis/diagnóstico , Anticuerpos Monoclonales/análisis , Anticuerpos Monoclonales/inmunología , Biomarcadores/análisis , Médula Ósea/inmunología , Antígenos CD2/inmunología , Recuento de Células , Colorantes Fluorescentes/análisis , Colorantes Fluorescentes/química , Humanos , Subunidad alfa del Receptor de Interleucina-2/inmunología , Mastocitos/inmunología , Mastocitos/metabolismo , Mastocitosis/clasificación , Mastocitosis/inmunologíaRESUMEN
BACKGROUND: According to the World Health Organization (WHO) classification the diagnosis of systemic mastocytosis (SM) relies on bone marrow (BM) examination and is based on one major and four minor criteria. Herein, we used WHO criteria to compare flow cytometry (FC) with other available techniques in the diagnosis of SM after BM examination. METHODS: We analyzed a cohort of 95 patients with suspect SM. All patients underwent comprehensive BM examination by using cytology, immunohistochemistry, FC and molecular study for mutation of c-Kit and serum tryptase dosage. FC evaluation was based on a combination of monoclonal antibodies, specifically CD25/CD2/CD45/CD34/CD117. RESULTS: Seventy-four out of ninety-five patients were diagnosed with indolent SM (n = 59) or monoclonal mast cell activation syndrome (n = 15) because satisfying less than 3 minor criteria. Thirty-nine out of these seventy-four patients fulfilled the major histological criterion, whereas the presence of a minor criterion was assessed by FC, molecular study, cytology, and tryptase level in 70/74, 52/67, 56/74, and 42/74 patients, respectively. FC showed higher sensitivity than IHC in detection of CD25+ mast cells (MC) (92.9% vs. 73.8%; P = 0.019), especially in the absence of the major histological criterion (90.5% vs. 47.6%; P = 0.003). Moreover, CD2 expression was documented by FC and IHC in 97.1% and 35.3% of cases, respectively (P < 0.001). CONCLUSIONS: FC showed the best sensitivity for identifying abnormal MC compared to other techniques, especially in cases with low MC burden. Therefore, we hope for a major role of FC in the diagnostic work-up of clonal MC disorders.
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Citometría de Flujo , Inmunofenotipificación/métodos , Mastocitosis Sistémica/diagnóstico , Adulto , Anciano , Biomarcadores/análisis , Células de la Médula Ósea/citología , Células de la Médula Ósea/inmunología , Antígenos CD2/análisis , Antígenos CD2/inmunología , Femenino , Humanos , Inmunohistoquímica , Subunidad alfa del Receptor de Interleucina-2/análisis , Subunidad alfa del Receptor de Interleucina-2/inmunología , Masculino , Mastocitos/química , Mastocitos/inmunología , Mastocitosis Sistémica/sangre , Mastocitosis Sistémica/genética , Mastocitosis Sistémica/inmunología , Persona de Mediana Edad , Mutación , Proteínas Proto-Oncogénicas c-kit/genética , Sensibilidad y Especificidad , Organización Mundial de la Salud , Adulto JovenRESUMEN
Plasmacytoid dendritic cells (pDCs) are decreased in number and are functionally impaired in HIV act reasons for pDCs depletion are still unknown. It was recently reported that pDCs can be divided into two functionally distinct populations based on their CD2 expression level. To determine how the CD2(high) and CD2(low) populations are affected by HIV infection, we analyzed their frequencies in the peripheral blood of HIV-infected subjects and healthy controls. We found that the CD2(low) pDC subset was preferentially depleted in infected individuals. The frequency of CD2(low) pDCs correlated with the CD4(+) T-cell count but not with the plasma viral load. This finding furthers our understanding of the causes and consequences of pDC depletion during HIV infection.
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Antígenos CD2/análisis , Linfocitos T CD4-Positivos/patología , Linaje de la Célula/inmunología , Células Dendríticas/patología , Infecciones por VIH/patología , VIH/fisiología , Adolescente , Adulto , Anciano , Antígenos CD2/inmunología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/virología , Estudios de Casos y Controles , Recuento de Células , Niño , Células Dendríticas/inmunología , Células Dendríticas/virología , Citometría de Flujo , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Humanos , Persona de Mediana Edad , ARN Viral/análisis , ARN Viral/biosíntesis , Carga Viral/inmunologíaRESUMEN
We sought to determine the effects of interleukin-2 administered in combination with antiretroviral therapy (ART) on CD4+ T cells in the gut. Lymphocytes from whole blood, colon, and terminal ileum of HIV-infected adults treated with interleukin-2 and ART or ART alone were examined. There were no differences between groups in the proportion of CD4+ T cells or in expression of CD25 or Ki67 by CD4+ T cells in the gut. Although IL-2 administration leads to expansion of peripheral blood CD4+ T cells, there is no alteration in the proportion or activation of CD4+ T cells in the gut mucosa.