RESUMEN
SARS-CoV-2 breakthrough infections, associated with waning immunity, increase systemic antibody levels. In this study, we analyzed the impact of the infection timing on the magnitude of the systemic humoral response and whether breakthrough infections also boost antibody levels in the salivary compartment. We observed that the combination of infection plus vaccination, regardless of infection timing, produced a sharp increase in systemic antibodies, which were higher in subjects infected after third doses. Moreover, despite high systemic antibody levels, breakthrough infections after dose three occurred and boosted antibody levels in the salivary compartment. These results suggest that current vaccination strategies against COVID-19 should be improved. Results also showed that determination of salivary antibodies against SARS-CoV-2 could be a valuable tool in disease prevalence studies, for the follow-up of vaccinated individuals, and to assist vaccination strategies against COVID-19, especially in settings where blood sampling cannot be fulfilled.
RESUMEN
We report the alterations of immunological parameters of a patient with visceral leishmaniasis caused by Leishmania (Leishmania) infantum from the Northwest of Argentina during active disease and after achieving clinical recovery. We first demonstrated elevated amounts of IFN-y, IL-10, B-cell activating factor (BAFF) and IgG in plasma during active disease, which returned to control values after recovery. In relation to T cell profile, we measured CD27, CD28, CD45RO, CD57 and perforin. We found a highly differentiated phenotype, preferentially in active disease and among CD8+ T cells, consisting in increased numbers of late differentiated and terminal effector cells. Although this highly differentiated CD8+ T cell phenotype persisted after recovery, a clear increase of central memory cells was recorded for both T subsets at that point, suggesting signs of reversion toward a less differentiated profile. The composition of the B cell compartment was slightly modified during active disease. Herein we document the global impact of severe visceral leishmaniasis on immunological parameters, which tend to revert upon clinical recovery, suggesting signs of immune restoration accompanying clinical improvement. The evaluated parameters could eventually be used as biomarkers of clinical evolution of visceral leishmaniasis.
En el presente trabajo informamos la afectación de parámetros inmunológicos durante la etapa grave de la infección y luego de alcanzar la recuperación clínica en un paciente autóctono del Noroeste argentino con leishmaniasis visceral causada por Leishmania (Leishmania) infantum. Detectamos concentraciones plasmáticas elevadas de interferón-y, interleuquina 10, IgG y BAFF (B-cell activating factor) durante la enfermedad activa, que se normalizaron luego de la recuperación clínica. En relación al perfil de diferenciación y memoria de las células T, clasificamos las células según la expresión de CD27, CD28, CD45RO, CD57 y perforina. Encontramos un fenotipo altamente diferenciado analizando la población de linfocitos T CD8+, con porcentajes aumentados de células T de diferenciación tardía y efectoras terminales. Si bien el fenotipo T CD8+ persistió luego de la recuperación clínica, pudimos observar un claro aumento de células T de memoria central en ese punto de estudio, sugiriendo signos de una posible reversión hacia un perfil T menos avanzado. El compartimiento de células B CD19+ mostró cambios más leves en la composición de las subpoblaciones de memoria. Documentamos el compromiso global de parámetros inmunológicos en la etapa grave de la leishmaniasis visceral que tienden a revertir luego de la recuperación, sugiriendo posibles signos de reconstitución inmune acompañando a la mejoría clínica. Los parámetros evaluados podrían ser útiles como biomarcadores de la evolución clínica de la enfermedad.
Asunto(s)
Leishmaniasis Visceral , Argentina , Linfocitos T CD8-positivos , HumanosRESUMEN
Resumen En el presente trabajo informamos la afectación de parámetros inmunológicos durante la etapa grave de la infección y luego de alcanzar la recuperación clínica en un paciente autóctono del Noroeste argentino con leishmaniasis visceral causada por Leishmania (Leishmania) infantum. Detectamos concentraciones plasmáticas elevadas de interferón-γ, interleuquina 10, IgG y BAFF (B-cell activating factor) durante la enfermedad activa, que se normalizaron luego de la recuperación clínica. En relación al perfil de diferenciación y memoria de las células T, clasificamos las células según la expresión de CD27, CD28, CD45RO, CD57 y perforina. Encontramos un fenotipo altamente diferenciado analizando la población de linfocitos T CD8+, con porcentajes aumentados de células T de diferenciación tardía y efectoras terminales. Si bien el fenotipo T CD8+ persistió luego de la recuperación clínica, pudimos observar un claro aumento de células T de memoria central en ese punto de estudio, sugiriendo signos de una posible reversión hacia un perfil T menos avanzado. El compartimiento de células B CD19+ mostró cambios más leves en la composición de las subpoblaciones de memoria. Documentamos el compromiso global de parámetros inmunológicos en la etapa grave de la leishmaniasis visceral que tienden a revertir luego de la recuperación, sugiriendo posibles signos de reconstitución inmune acompañando a la mejoría clínica. Los parámetros evaluados podrían ser útiles como biomarcadores de la evolución clínica de la enfermedad.
Abstract We report the alterations of immunological parameters of a patient with visceral leishmaniasis caused by Leishmania (Leishmania) infantum from the Northwest of Argentina during active disease and after achieving clinical recovery. We first demonstrated elevated amounts of IFN-γ, IL-10, B-cell activating factor (BAFF) and IgG in plasma during active disease, which returned to control values after recovery. In relation to T cell profile, we measured CD27, CD28, CD45RO, CD57 and perforin. We found a highly differentiated phenotype, preferentially in active disease and among CD8+ T cells, consisting in increased numbers of late differentiated and terminal effector cells. Although this highly differentiated CD8+ T cell phenotype persisted after recovery, a clear increase of central memory cells was recorded for both T subsets at that point, suggesting signs of reversion toward a less differentiated profile. The composition of the B cell compartment was slightly modified during active disease. Herein wedocument the global impact of severe visceral leishmaniasis on immunological parameters, which tend to revert upon clinical recovery, suggesting signs of immune restoration accompanying clinical improvement. The evaluated parameters could eventually be used as biomarkers of clinical evolution of visceral leishmaniasis.
Asunto(s)
Humanos , Leishmaniasis Visceral , Argentina , Linfocitos T CD8-positivosRESUMEN
AIMS: The aim of this study was to evaluate characteristics of B cells in human tegumentary leismaniasis (TL) analysing cutaneous leishmaniasis (CL), most prevalent form and mucosal leishmaniasis (ML), aggressive form characterized by the destruction of the oral-nasal-pharyngeal cavities. METHODS AND RESULTS: By flow cytometry analysis, we found decreased percentages of non-class-switched memory B cells in TL with the degree of the loss related to clinical severity. Using commercial ELISA, we reported high levels of B-cell activating factor (BAFF) and IgG preferentially in aggressive CL and markedly in ML together with decreased BAFF receptors in the latter. We also found lower levels of BAFF after clinical recovery suggesting a relation between BAFF and disease activity. Mucosal leishmaniasis history of therapeutic failure presented high levels of BAFF accompanied by detectable concentrations of IFN-γ and IL-6 (assayed by commercial ELISA and cytometric bead arrays respectively), cytokines involved in exaggerated inflammatory responses and tissue damage in TL. CONCLUSION: We demonstrate B-cell disturbances in TL with the degree of the alterations related to clinical severity. We suggest a relation between excess of BAFF and disease activity and point towards a possible implication of BAFF in the inflammatory phenomenon of ML.
Asunto(s)
Factor Activador de Células B/metabolismo , Linfocitos B/inmunología , Leishmaniasis Cutánea/inmunología , Adolescente , Adulto , Anciano , Receptor del Factor Activador de Células B/metabolismo , Citocinas/metabolismo , Femenino , Humanos , Inmunoglobulina G/inmunología , Leishmaniasis Mucocutánea/inmunología , Masculino , Persona de Mediana Edad , Adulto JovenAsunto(s)
Linfocitos B , Recuento de Linfocitos , Trastornos Linfoproliferativos/sangre , Trastornos Linfoproliferativos/diagnóstico , Progresión de la Enfermedad , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/virología , Humanos , Memoria Inmunológica , Trastornos Linfoproliferativos/tratamiento farmacológico , Trastornos Linfoproliferativos/etiología , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Carga ViralRESUMEN
CD4+ T follicular helper cells (TFH) were assessed in adult patients with common variable immune deficiency (CVID) classified according to the presence of granulomatous disease (GD), autoimmunity (AI), or both GD and AI (Group I) or the absence of AI and GD (Group II). TFH lymphocytes were characterized by expression of CXCR5 and PD-1. TFH were higher (in both absolute number and percentage) in Group I than in Group II CVID patients and normal controls (N). Within CXCR5+CD4+ T cells, the percentage of PD-1 (+) was higher and that of CCR7 (+) was lower in Group I than in Group II and N. The percentages of Treg and TFH reg were similar in both CVID groups and in N. TFH responded to stimulation increasing the expression of the costimulatory molecules CD40L and ICOS as did N. After submitogenic PHA+IL-2 stimulation, intracellular expression of TFH cytokines (IL-10, IL-21) was higher than N in Group I, and IL-4 was higher than N in Group II. These results suggest that TFH are functional in CVID and highlight the association of increased circulating TFH with AI and GD manifestations.
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Inmunodeficiencia Variable Común/inmunología , Regulación de la Expresión Génica/inmunología , Enfermedad Granulomatosa Crónica/inmunología , Linfocitos T Colaboradores-Inductores/inmunología , Linfocitos T Reguladores/inmunología , Adulto , Anciano , Autoinmunidad , Ligando de CD40/genética , Ligando de CD40/inmunología , Estudios de Casos y Controles , Inmunodeficiencia Variable Común/complicaciones , Inmunodeficiencia Variable Común/genética , Inmunodeficiencia Variable Común/patología , Femenino , Enfermedad Granulomatosa Crónica/complicaciones , Enfermedad Granulomatosa Crónica/genética , Enfermedad Granulomatosa Crónica/patología , Humanos , Proteína Coestimuladora de Linfocitos T Inducibles/genética , Proteína Coestimuladora de Linfocitos T Inducibles/inmunología , Interleucina-10/genética , Interleucina-10/inmunología , Interleucina-2/farmacología , Interleucina-4/genética , Interleucina-4/inmunología , Interleucinas/genética , Interleucinas/inmunología , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Fitohemaglutininas/farmacología , Cultivo Primario de Células , Receptor de Muerte Celular Programada 1/genética , Receptor de Muerte Celular Programada 1/inmunología , Receptores CCR7/genética , Receptores CCR7/inmunología , Receptores CXCR5/genética , Receptores CXCR5/inmunología , Transducción de Señal , Linfocitos T Colaboradores-Inductores/efectos de los fármacos , Linfocitos T Colaboradores-Inductores/patología , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T Reguladores/patologíaRESUMEN
American tegumentary leishmaniasis displays two main clinical forms: cutaneous (CL) and mucosal (ML). ML is more resistant to treatment and displays a more severe and longer evolution. Since both forms are caused by the same Leishmania species, the immunological response of the host may be an important factor determining the evolution of the disease. Herein, we analyzed the differentiation and memory profile of peripheral CD4(+) and CD8(+) T lymphocytes of patients with CL and ML and their Leishmania-T. cruzi co-infected counterparts. We measured the expression of CD27, CD28, CD45RO, CD127, PD-1 and CD57, together with interferon-γ and perforin. A highly differentiated phenotype was reflected on both T subsets in ML and preferentially on CD8(+) T cells in CL. A positive trend toward a higher T differentiation profile was found in T. cruzi-infected CL and ML patients as compared with Leishmania single infections. Association between CD8(+) T-cell differentiation and illness duration was found within the first year of infection, with progressive increase of highly differentiated markers over time. Follow-up of patients with good response to therapy showed predominance of early differentiated CD8(+) T cells and decrease of highly differentiated cells, while patients with frequent relapses presented the opposite pattern. CD8(+) T cells showed the most striking changes in their phenotype during leishmaniasis. Patients with long-term infections showed the highest differentiated degree implying a relation between T differentiation and parasite persistence. Distinct patterns of CD8(+) T differentiation during follow-up of different clinical outcomes suggest the usefulness of this analysis in the characterization of Leishmania-infected patients.
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Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Enfermedad de Chagas/patología , Coinfección/patología , Leishmaniasis Mucocutánea/patología , Subgrupos de Linfocitos T/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD/análisis , Diferenciación Celular , Niño , Femenino , Estudios de Seguimiento , Humanos , Inmunofenotipificación , Interferón gamma/análisis , Masculino , Persona de Mediana Edad , Perforina/análisis , Adulto JovenRESUMEN
Peripheral blood mononuclear cells with T(FH) phenotype from two asymptomatic XLP patients were studied. Normal/high numbers of CXCR5+, CD4+ T cells coexpressing PD-1 were demonstrated. Peripheral blood mononuclear cells (PBMC) from these patients responded to sub-optimal PHA/IL-2 stimulation upregulating ICOS and CD40L and increasing intracellular expression of IL-10, IL-21 and IL-4 by CD4+ T(FH) cells. However when compared to N, the time profile of activation and cytokine synthesis was different in XLP and N. While ICOS and CD40L expression in N decreased after 6-8 days, it continued to increase or was maintained in XLP cultures. Intracellular IL-10, IL-21 and IL-4 reached higher values in XLP than N after 8 days. Rather than the absence of T(FH) cells or their intrinsic inability to respond to stimuli, differences in the time profile of their response could contribute to impair their role as helpers of B lymphocytes.
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Linfocitos T CD4-Positivos/inmunología , Péptidos y Proteínas de Señalización Intracelular/inmunología , Trastornos Linfoproliferativos/inmunología , Adulto , Linfocitos T CD4-Positivos/efectos de los fármacos , Ligando de CD40/biosíntesis , Ligando de CD40/inmunología , Células Cultivadas , Exones , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Proteína Coestimuladora de Linfocitos T Inducibles/biosíntesis , Proteína Coestimuladora de Linfocitos T Inducibles/inmunología , Interleucina-2/inmunología , Interleucina-2/farmacología , Interleucinas/inmunología , Interleucinas/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Leucocitos Mononucleares/inmunología , Trastornos Linfoproliferativos/tratamiento farmacológico , Trastornos Linfoproliferativos/genética , Persona de Mediana Edad , Mutación , Fitohemaglutininas/inmunología , Fitohemaglutininas/farmacología , Proteína Asociada a la Molécula de Señalización de la Activación Linfocitaria , Linfocitos T Colaboradores-Inductores/inmunología , Regulación hacia Arriba/inmunologíaRESUMEN
Occurrence of the rare CD16b deficiency ("null" phenotype) in neutrophils from two female patients (41 and 15 years old) is reported. The first case was referred with a diagnosis of anemia related to paroxistic nocturnal hemoglobinuria and the second case, with presumptive diagnosis of immune neutropenia. In both cases, absence of CD16b expression was determined by flow cytometry without deficiencies of other neutrophil alloantigens or defects of membrane anchorage through glycosil phosphatydil inositol (GPI) linkage. Clinical manifestations in both patients could not be attributed exclusively to the absence of CD16b, as other receptors for the IgG Fc fragment (CD32 and CD64) could compensate this deficiency that occurs in <1% of the caucasic population. Nevertheless, it is important to take this rare deficiency into account in order to prevent isoantibody formation after eventual blood transfusions, or transient neonatal immune neutropenia in children born to women with the "null" phenotype.
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Hemoglobinuria Paroxística/diagnóstico , Neutropenia/diagnóstico , Neutrófilos/inmunología , Receptores de IgG/deficiencia , Adolescente , Adulto , Femenino , Citometría de Flujo , Proteínas Ligadas a GPI , Hemoglobinuria Paroxística/inmunología , Humanos , Receptores de IgG/inmunologíaRESUMEN
Survival of lymphocytes after prolonged culture was studied in two asymptomatic XLP patients. Viability of XLP PBMC after 30 days of non-stimulated culture was higher than that of normal controls (N), mainly due to the persistence of CD8 memory lymphocytes. IFNgamma high CD8 T lymphocytes remained higher in XLP than in N after 30 days. The number of perforin+ CD8 lymphocytes was markedly reduced after 30 days in XLP and in N. Increased viability was not related to CD127, PD-1, CD27, or CD62L expression. Concerning B lymphocytes, memory CD27+ CD19+ cells prevailed over CD27- cells after 30 days in both XLP and N, with far more surviving cells in XLP. In N, few CD19+ B lymphocytes were viable after prolonged culture. In XLP, these cells were also IgD+, IgM+ and EBNA2+. These results demonstrate that IFNgamma-positive memory CD8 T cells persist in XLP after prolonged culture in association with a subset of viable memory CD27+ B cells expressing latent EBV antigens. The survival advantage of XLP cells might be related to increased frequency of extranodal lymphoma in XLP patients.
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Linfocitos B/patología , Linfocitos T CD4-Positivos/patología , Linfocitos T CD8-positivos/patología , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Trastornos Linfoproliferativos/patología , Adulto , Antígenos CD/metabolismo , Proteínas Reguladoras de la Apoptosis/metabolismo , Linfocitos B/inmunología , Linfocitos B/virología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/virología , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/virología , Supervivencia Celular , Células Cultivadas , Cromosomas Humanos X/genética , Infecciones por Virus de Epstein-Barr/complicaciones , Humanos , Interferón gamma/metabolismo , Subunidad alfa del Receptor de Interleucina-7/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Trastornos Linfoproliferativos/inmunología , Trastornos Linfoproliferativos/virología , Perforina/metabolismo , Receptor de Muerte Celular Programada 1 , Proteína Asociada a la Molécula de Señalización de la Activación LinfocitariaRESUMEN
UNLABELLED: We have analysed the phenotype of T lymphocytes in two X-linked lymphoproliferative disease (XLP) patients with the same SH2D1A mutation differing in initial exposure to Epstein-Barr virus (EBV) and treatment. While memory T lymphocytes (with low CCR7 and CD62L expression) prevailed in both XLP patients, in patient 9, who developed acute infectious mononucleosis (AIM) and received B cell ablative treatment, the predominant phenotype was that of late effector CD8 T cells (CD27-, CD28-, CCR7-, CD62L-, CD45 RA+, perforin+), while in patient 4 (who did not suffer AIM) the prevalent phenotype of CD8 T lymphocytes was similar to that of normal controls (N) or to that of adult individuals who recovered from AIM: CD27+ , CD28+, CCR7-, CD62L-, CD45 RO+ and perforin-. CD57 expression (related to senescence) was also higher in CD8 T cells from patient 9 than in patient 4, AIM or N. Persistently high EBV viral load was observed in patient 9. The results obtained from this limited number of XLP patients suggest that events related to the initial EBV encounter (antigen load, treatment, cytokine environment) may have more weight than lack of SH2D1A in determining the long-term differentiation pattern of CD8 memory T cells.
Asunto(s)
Linfocitos T CD8-positivos/inmunología , Enfermedades Genéticas Ligadas al Cromosoma X/inmunología , Trastornos Linfoproliferativos/inmunología , Adulto , Ligando CD27/sangre , Antígenos CD28/sangre , Linfocitos T CD4-Positivos/inmunología , Preescolar , Enfermedades Genéticas Ligadas al Cromosoma X/virología , Herpesvirus Humano 4/aislamiento & purificación , Humanos , Memoria Inmunológica , Inmunofenotipificación , Mononucleosis Infecciosa/complicaciones , Mononucleosis Infecciosa/inmunología , Interferón gamma/biosíntesis , Trastornos Linfoproliferativos/virología , Masculino , Miembro 7 de la Superfamilia de Receptores de Factores de Necrosis Tumoral/sangre , Carga ViralRESUMEN
Human immune deficiency virus (HIV) and human hepatitis C virus (HCV) infection are frequent in patients who have been exposed to blood or blood-derived products. It has been suggested that HIV infection increases HCV replication altering the course of HCV-related disease. However, it is not known if HIV directly enhances HCV replication or if its effect is the consequence of HIV infection of other cell types that control HCV replication (lymphocytes, macrophages). While the main cell targets for HIV infection are mononuclear leukocytes bearing CD4 and the chemokine receptors CCR5 and CXCR4, HCV was originally thought to be strictly hepatotropic, but it is now known that HCV can also replicate in peripheral blood mononuclear cells (PBMC). Therefore, in co-infected individuals, these two different viruses could share cell targets and interact either directly or indirectly. Some membrane receptors can be used by both HCV and HIV for entry into target cells, but the intracellular mechanisms shared by these viruses are not known. Lack of experimental systems providing suitable methods for the study of HCV replication in the presence or absence of HIV co-infection has hampered advances in this research area, but recent investigations are currently going on in order to answer these questions. This is an important issue, as knowledge of HIV/HCV interactions is required for the design of effective antiviral therapies.
Asunto(s)
Infecciones por VIH/inmunología , Hepatitis C/inmunología , Replicación Viral , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Células Dendríticas/fisiología , Células Dendríticas/virología , Infecciones por VIH/virología , Hepacivirus/fisiología , HumanosRESUMEN
Auto or alloantibodies reactive with neutrophils define immune neutropenia. Alloimmune neonatal neutropenia is caused by maternal sensitization to paternal neutrophil antigens, resulting in IgG antibodies that are transferred to the fetus through the placenta. We present the studies in 4 children from 3 families with neutropenia of unknown origin (two of them were brothers). They were evaluated by flow cytometry in parallel with leukoagglutination. Reference values were established for serum reactive IgG in healthy volunteers for three dilutions (1/2, 1/5 and 1/20), both for the autologous reaction (serum and cells of the same individual) and for the heterologous reaction (serum and cells of different individuals). Results were expressed by an index defined by the quotient of the mean fluorescence intensity of the patient's serum divided by that of the reference serum. Serum reactive/agglutinant factors and circulating immune complexes were evaluated in patients and parents serum. Neutrophil specific phenotypes were determined for HNA-1a, HNA-1b and HNA-2a. Reactive IgG/agglutinant factors were found in 4 children. Two maternal sera were reactive against paternal and/or children neutrophils. Circulating immune complexes were detected in 2/4 children sera and were negative in 3/3 maternal sera. Maternal/children incompatibility was detected in the four cases. The three mothers had the same phenotype: homozygous NA1/NA1, NB1+.
Asunto(s)
Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Inmunoglobulina G/sangre , Neutropenia/inmunología , Neutrófilos/inmunología , Aglutinación/inmunología , Anticuerpos Anticitoplasma de Neutrófilos/sangre , Eosinófilos/metabolismo , Femenino , Citometría de Flujo/métodos , Factor Estimulante de Colonias de Granulocitos , Humanos , Lactante , Recuento de Leucocitos , Masculino , Neutropenia/sangre , Neutrófilos/metabolismo , Fenotipo , Embarazo , Proteínas Recombinantes , Valores de ReferenciaRESUMEN
La neutropenia inmune se diagnostica por la presencia de auto o aloanticuerpos reactivos con losneutrófilos. La neutropenia aloinmune neonatal es consecuencia de la sensibilización materna alos antígenos específicos de los neutrófilos paternos que afectan al neonato al atravesar la barrera placentaria. Se presentan 4 casos de niños, 2 de ellos hermanos consanguíneos con doble vínculo. Se estudiaron los sueros de los pacientes y sus padres. Por citometría de flujo se establecen los valores de referencia de la IgG sérica reactiva con los neutrófilos en voluntarios sanos, para 3 diluciones (1/2, 1/5 y 1/20) en reacción autóloga(suero y células de un mismo individuo) y heteróloga (suero y células de diferentes individuos). Los resultadosse expresan por un índice definido como el cociente entre la mediana de la intensidad de fluorescencia media del suero incógnita y la de un suero utilizado como referencia. Por leucoaglutinación se evaluó la dilucióndel suero 1/20. Se determinó el nivel de complejos inmunes circulantes. Se determinó el fenotipo, para los epitopes HNA-1a, HNA-1b y HNA-2a. En los 4 niños se encontró IgG reactiva y/o factores aglutinantes; 2/3 sueros maternos fueron reactivos con los neutrófilos del cónyuge y de los hijos. Los complejos inmunes circulantes fueron positivos en 2/4 sueros negativos en 3/3 sueros maternos. Se encontró incompatibilidad materno-infantil en los 4 casos. Las 3 madres tenían igual fenotipo: homocigotos NA1/NA1, NB1+. En síntesis, se presenta el hallazgo de 4 casos con neutropenia inmune: 3/4 auto-inmune, 1/3 se asocia a complejos inmunes circulantes y 1/4 con neutropenia neonatal aloinmune
Auto or alloantibodies reactive with neutrophils define immune neutropenia. Alloimmune neonatal neutropenia is caused by maternal sensitization to paternal neutrophil antigens, resulting in IgG antibodies that are transferred to the fetus through the placenta. We present the studies in 4 children from 3 families with neutropenia of unknown origin (two of them were brothers). Theywere evaluated by flow cytometry in parallel with leukoagglutination. Reference values were established forserum reactive IgG in healthy volunteers for three dilutions (1/2, 1/5 and 1/20), both for the autologous reaction (serum and cells of the same individual) and for the heterologous reaction (serum and cells of differentindividuals). Results were expressed by an index defined by the quotient of the mean fluorescence intensityof the patients serum divided by that of the reference serum. Serum reactive/agglutinant factors and circulating immune complexes were evaluated in patients and parents serum. Neutrophil specific phenotypes weredetermined for HNA-1a, HNA-1b and HNA-2a. Reactive IgG/agglutinant factors were found in 4 children. Twomaternal sera were reactive against paternal and/or children neutrophils. Circulating immune complexes weredetected in 2/4 children sera and were negative in 3/3 maternal sera. Maternal/children incompatibility wasdetected in the four cases. The three mothers had the same phenotype: homozygous NA1/NA1, NB1+
Asunto(s)
Humanos , Masculino , Femenino , Embarazo , Lactante , Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Citometría de Flujo/métodos , Inmunoglobulina G/sangre , Neutropenia/inmunología , Neutrófilos/inmunología , Aglutinación/inmunología , Anticuerpos Anticitoplasma de Neutrófilos/sangre , Eosinófilos/metabolismo , Recuento de Leucocitos , Neutropenia/sangre , Neutrófilos/metabolismo , Fenotipo , Valores de ReferenciaRESUMEN
La neutropenia inmune se diagnostica por la presencia de auto o aloanticuerpos reactivos con losneutrófilos. La neutropenia aloinmune neonatal es consecuencia de la sensibilización materna alos antígenos específicos de los neutrófilos paternos que afectan al neonato al atravesar la barrera placentaria. Se presentan 4 casos de niños, 2 de ellos hermanos consanguíneos con doble vínculo. Se estudiaron los sueros de los pacientes y sus padres. Por citometría de flujo se establecen los valores de referencia de la IgG sérica reactiva con los neutrófilos en voluntarios sanos, para 3 diluciones (1/2, 1/5 y 1/20) en reacción autóloga(suero y células de un mismo individuo) y heteróloga (suero y células de diferentes individuos). Los resultadosse expresan por un índice definido como el cociente entre la mediana de la intensidad de fluorescencia media del suero incógnita y la de un suero utilizado como referencia. Por leucoaglutinación se evaluó la dilucióndel suero 1/20. Se determinó el nivel de complejos inmunes circulantes. Se determinó el fenotipo, para los epitopes HNA-1a, HNA-1b y HNA-2a. En los 4 niños se encontró IgG reactiva y/o factores aglutinantes; 2/3 sueros maternos fueron reactivos con los neutrófilos del cónyuge y de los hijos. Los complejos inmunes circulantes fueron positivos en 2/4 sueros negativos en 3/3 sueros maternos. Se encontró incompatibilidad materno-infantil en los 4 casos. Las 3 madres tenían igual fenotipo: homocigotos NA1/NA1, NB1+. En síntesis, se presenta el hallazgo de 4 casos con neutropenia inmune: 3/4 auto-inmune, 1/3 se asocia a complejos inmunes circulantes y 1/4 con neutropenia neonatal aloinmune (AU)
Auto or alloantibodies reactive with neutrophils define immune neutropenia. Alloimmune neonatal neutropenia is caused by maternal sensitization to paternal neutrophil antigens, resulting in IgG antibodies that are transferred to the fetus through the placenta. We present the studies in 4 children from 3 families with neutropenia of unknown origin (two of them were brothers). Theywere evaluated by flow cytometry in parallel with leukoagglutination. Reference values were established forserum reactive IgG in healthy volunteers for three dilutions (1/2, 1/5 and 1/20), both for the autologous reaction (serum and cells of the same individual) and for the heterologous reaction (serum and cells of differentindividuals). Results were expressed by an index defined by the quotient of the mean fluorescence intensityof the patientãs serum divided by that of the reference serum. Serum reactive/agglutinant factors and circulating immune complexes were evaluated in patients and parents serum. Neutrophil specific phenotypes weredetermined for HNA-1a, HNA-1b and HNA-2a. Reactive IgG/agglutinant factors were found in 4 children. Twomaternal sera were reactive against paternal and/or children neutrophils. Circulating immune complexes weredetected in 2/4 children sera and were negative in 3/3 maternal sera. Maternal/children incompatibility wasdetected in the four cases. The three mothers had the same phenotype: homozygous NA1/NA1, NB1+ (AU)
Asunto(s)
Humanos , Masculino , Femenino , Embarazo , Lactante , Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Citometría de Flujo/métodos , Inmunoglobulina G/sangre , Neutropenia/inmunología , Neutrófilos/inmunología , Aglutinación/inmunología , Anticuerpos Anticitoplasma de Neutrófilos/sangre , Eosinófilos/metabolismo , Factor Estimulante de Colonias de Granulocitos , Recuento de Leucocitos , Neutropenia/sangre , Neutrófilos/metabolismo , Fenotipo , Valores de ReferenciaRESUMEN
La neutropenia inmune se diagnostica por la presencia de auto o aloanticuerpos reactivos con losneutrófilos. La neutropenia aloinmune neonatal es consecuencia de la sensibilización materna alos antígenos específicos de los neutrófilos paternos que afectan al neonato al atravesar la barrera placentaria. Se presentan 4 casos de niños, 2 de ellos hermanos consanguíneos con doble vínculo. Se estudiaron los sueros de los pacientes y sus padres. Por citometría de flujo se establecen los valores de referencia de la IgG sérica reactiva con los neutrófilos en voluntarios sanos, para 3 diluciones (1/2, 1/5 y 1/20) en reacción autóloga(suero y células de un mismo individuo) y heteróloga (suero y células de diferentes individuos). Los resultadosse expresan por un índice definido como el cociente entre la mediana de la intensidad de fluorescencia media del suero incógnita y la de un suero utilizado como referencia. Por leucoaglutinación se evaluó la dilucióndel suero 1/20. Se determinó el nivel de complejos inmunes circulantes. Se determinó el fenotipo, para los epitopes HNA-1a, HNA-1b y HNA-2a. En los 4 niños se encontró IgG reactiva y/o factores aglutinantes; 2/3 sueros maternos fueron reactivos con los neutrófilos del cónyuge y de los hijos. Los complejos inmunes circulantes fueron positivos en 2/4 sueros negativos en 3/3 sueros maternos. Se encontró incompatibilidad materno-infantil en los 4 casos. Las 3 madres tenían igual fenotipo: homocigotos NA1/NA1, NB1+. En síntesis, se presenta el hallazgo de 4 casos con neutropenia inmune: 3/4 auto-inmune, 1/3 se asocia a complejos inmunes circulantes y 1/4 con neutropenia neonatal aloinmune (AU)
Auto or alloantibodies reactive with neutrophils define immune neutropenia. Alloimmune neonatal neutropenia is caused by maternal sensitization to paternal neutrophil antigens, resulting in IgG antibodies that are transferred to the fetus through the placenta. We present the studies in 4 children from 3 families with neutropenia of unknown origin (two of them were brothers). Theywere evaluated by flow cytometry in parallel with leukoagglutination. Reference values were established forserum reactive IgG in healthy volunteers for three dilutions (1/2, 1/5 and 1/20), both for the autologous reaction (serum and cells of the same individual) and for the heterologous reaction (serum and cells of differentindividuals). Results were expressed by an index defined by the quotient of the mean fluorescence intensityof the patientãs serum divided by that of the reference serum. Serum reactive/agglutinant factors and circulating immune complexes were evaluated in patients and parents serum. Neutrophil specific phenotypes weredetermined for HNA-1a, HNA-1b and HNA-2a. Reactive IgG/agglutinant factors were found in 4 children. Twomaternal sera were reactive against paternal and/or children neutrophils. Circulating immune complexes weredetected in 2/4 children sera and were negative in 3/3 maternal sera. Maternal/children incompatibility wasdetected in the four cases. The three mothers had the same phenotype: homozygous NA1/NA1, NB1+ (AU)
Asunto(s)
Humanos , Masculino , Femenino , Embarazo , Lactante , Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Citometría de Flujo/métodos , Inmunoglobulina G/sangre , Neutropenia/inmunología , Neutrófilos/inmunología , Aglutinación/inmunología , Anticuerpos Anticitoplasma de Neutrófilos/sangre , Eosinófilos/metabolismo , Factor Estimulante de Colonias de Granulocitos , Recuento de Leucocitos , Neutropenia/sangre , Neutrófilos/metabolismo , Fenotipo , Valores de ReferenciaRESUMEN
In addition to the CD4 molecule that binds to the human immunodeficiency virus type-1 (HIV-1) envelope glycoprotein gp120, productive HIV-1 infection requires interaction with cellular receptors for alpha- or beta- chemokines (CXCR4 and CCR5 respectively). Isolates of HIV-1 exhibit different tropism depending on the chemokine receptor type that they use to infect their cellular targets. HIV-1 strains that use preferentially CCR5 are known as R5 strains. They are more frequently found in asymptomatic individuals during the initial stages of the disease and are involved in the transmision of infection from mother to child. HIV-1 species using CXCR4 (X4 strains) are observed mainly in patients with advanced disease. While X4 isolates are associated with syncitium formation, in general R5 strains are not. Interaction of X4 and R5 with their specific receptors is necessary to establish productive HIV-1 infection and trigger a series of intracellular signals. Modulation of CXCR4 and CCR5 expression after HIV-1 infection is one of the results of such interaction and may have important consequences on the course of the infection. Down regulation of CCR5 and CXCR4 after HIV-1 infection could be the result of indirect events linked to HIV-1 infection, such as the induction of alpha- or beta-chemokines competing with the virions for receptor binding. They could also reflect direct effects of HIV-1 on chemokine-receptor turnover. In this review, the mechanisms of modulation of CXCR4 and CCR5 expression after HIV-1 infection will be discussed.
Asunto(s)
Regulación de la Expresión Génica , Infecciones por VIH/virología , VIH-1/inmunología , VIH-1/fisiología , Receptores CCR5/metabolismo , Receptores CXCR4/metabolismo , Receptores del VIH/metabolismo , Quimiocinas CC/metabolismo , Quimiocinas CXC/metabolismo , Regulación hacia Abajo , Proteína gp120 de Envoltorio del VIH/fisiología , Proteína gp41 de Envoltorio del VIH/fisiología , Humanos , Receptores CCR5/genética , Receptores CCR5/inmunología , Receptores CXCR4/genética , Receptores CXCR4/inmunología , Receptores del VIH/genética , Receptores del VIH/inmunologíaRESUMEN
Detailed longitudinal studies of patients with X-linked lymphoproliferative disease (XLP) may increase our understanding of the immunologic defects that contribute to the development of lymphoma and hypogammaglobulinemia in XLP. We describe progressive changes observed in immunoglobulin concentrations, lymphocyte subsets, and Epstein-Barr virus (EBV) loads occurring in a 2-year period in a newly infected, but otherwise healthy, carrier (patient 9). We compare these findings with those observed in the patient's brother, who had hypogammaglobulinemia and XLP (patient 4). Immunoglobulin G (IgG), IgM, and IgA concentrations increased in patient 9 during acute EBV infection, but thereafter they decreased steadily to concentrations consistent with hypogammaglobulinemia, reaching a plateau 5 months after infection. In both patients, CD19+ B-lymphocyte rates remained lower than 3%, with a contraction of the B-cell memory compartment (CD27+ CD19+/CD19+) to 20% (normal range, 32%-56%). T-lymphocyte subpopulations showed a reduction in CD4+ T-cell counts and a permanent CD8+ T-cell expansion. Interestingly, CXCR3 memory TH1 cells were expanded and CCR4+ TH2 lymphocytes were reduced, suggesting that abnormal skewing of memory T-cell subsets might contribute to reduced antibody synthesis. Despite an expanded number of CD3+CD8+ lymphocytes, increased EBV loads occurred in both patients without overt clinical symptoms of mononucleosis, lymphoproliferative disease, or lymphoma.
Asunto(s)
Linfocitos B/metabolismo , Infecciones por Virus de Epstein-Barr/sangre , Herpesvirus Humano 4/metabolismo , Trastornos Linfoproliferativos/virología , Receptores de Quimiocina/biosíntesis , Linfocitos T/metabolismo , Miembro 7 de la Superfamilia de Receptores de Factores de Necrosis Tumoral/biosíntesis , Adulto , Antígenos CD19/biosíntesis , Complejo CD3/biosíntesis , Antígenos CD8/biosíntesis , Niño , Preescolar , Salud de la Familia , Humanos , Inmunoglobulina A/metabolismo , Inmunoglobulina G/metabolismo , Inmunoglobulina M/metabolismo , Memoria Inmunológica , Inmunofenotipificación , Linfoma/complicaciones , Trastornos Linfoproliferativos/genética , Masculino , Linaje , Polimorfismo de Longitud del Fragmento de Restricción , Receptores CCR4 , Receptores CXCR3 , Factores de TiempoRESUMEN
We studied the release of p24 antigen from peripheral blood mononuclear cell-derived monocyte/macrophages obtained from 13 HIV-positive patients receiving highly active antiretroviral therapy (HAART). Although HIV-infected monocyte/macrophages were detected in 80% of patients after 36 months of continuous treatment, additional exposure to HAART reduced the chance of detecting HIV-releasing monocyte/macrophages. Therefore, after more than 3 years of HAART, recently infected monocytes may play a less important role as a source of emerging HIV-1 upon HAART interruption.