Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 129
Filtrar
1.
J Allergy Clin Immunol ; 149(2): 569-578, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34958811

RESUMEN

Our understanding of risk factors and interventions influencing outcomes from coronavirus disease 2019 (COVID-19) has continued to evolve, revealing advances emerging from hypotheses formed at the start of the pandemic. Epidemiologic studies have shown that asthma control, rather than a diagnosis of asthma, is a determinant of COVID-19 severity. Clinical outcomes in patients with primary immunodeficiencies, even in those with impaired cellular immunity, are variable. IL-6 has emerged as a reliable biomarker of COVID-19 severity, and large clinical trials have shown the potential for improving outcomes through inhibition of IL-6 signaling in some patients. Studies of genetic risk factors for severe COVID-19 have also revealed the importance of interferon homeostasis in the defense against severe acute respiratory syndrome coronavirus 2. Because COVID-19 vaccines constitute the primary tool for ending this pandemic, strategies have been developed to address potential allergic and immune-mediated reactions. Here, we discuss advances in our understanding of COVID-19 risk factors and outcomes within the context of allergic and immunologic mechanisms.


Asunto(s)
Antivirales/uso terapéutico , Asma/terapia , Productos Biológicos/uso terapéutico , COVID-19/terapia , Síndromes de Inmunodeficiencia/terapia , SARS-CoV-2/efectos de los fármacos , Anticuerpos Monoclonales/uso terapéutico , Asma/inmunología , Asma/mortalidad , Asma/virología , Azetidinas/uso terapéutico , Biomarcadores/metabolismo , COVID-19/inmunología , COVID-19/mortalidad , COVID-19/virología , Vacunas contra la COVID-19/administración & dosificación , Humanos , Síndromes de Inmunodeficiencia/inmunología , Síndromes de Inmunodeficiencia/mortalidad , Síndromes de Inmunodeficiencia/virología , Proteína Antagonista del Receptor de Interleucina 1/uso terapéutico , Interleucina-6/antagonistas & inhibidores , Interleucina-6/genética , Interleucina-6/inmunología , Pronóstico , Purinas/uso terapéutico , Pirazoles/uso terapéutico , Factores de Riesgo , SARS-CoV-2/patogenicidad , Sulfonamidas/uso terapéutico , Análisis de Supervivencia , Resultado del Tratamiento
2.
J Allergy Clin Immunol ; 149(2): 557-561.e1, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34780850

RESUMEN

BACKGROUND: Patients with some types of immunodeficiency can experience chronic or relapsing infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This leads to morbidity and mortality, infection control challenges, and the risk of evolution of novel viral variants. The optimal treatment for chronic coronavirus disease 2019 (COVID-19) is unknown. OBJECTIVE: Our aim was to characterize a cohort of patients with chronic or relapsing COVID-19 disease and record treatment response. METHODS: We conducted a UK physician survey to collect data on underlying diagnosis and demographics, clinical features, and treatment response of immunodeficient patients with chronic (lasting ≥21 days) or relapsing (≥2 episodes) of COVID-19. RESULTS: We identified 31 patients (median age 49 years). Their underlying immunodeficiency was most commonly characterized by antibody deficiency with absent or profoundly reduced peripheral B-cell levels; prior anti-CD20 therapy, and X-linked agammaglobulinemia. Their clinical features of COVID-19 were similar to those of the general population, but their median duration of symptomatic disease was 64 days (maximum 300 days) and individual patients experienced up to 5 episodes of illness. Remdesivir monotherapy (including when given for prolonged courses of ≤20 days) was associated with sustained viral clearance in 7 of 23 clinical episodes (30.4%), whereas the combination of remdesivir with convalescent plasma or anti-SARS-CoV-2 mAbs resulted in viral clearance in 13 of 14 episodes (92.8%). Patients receiving no therapy did not clear SARS-CoV-2. CONCLUSIONS: COVID-19 can present as a chronic or relapsing disease in patients with antibody deficiency. Remdesivir monotherapy is frequently associated with treatment failure, but the combination of remdesivir with antibody-based therapeutics holds promise.


Asunto(s)
Adenosina Monofosfato/análogos & derivados , Alanina/análogos & derivados , Anticuerpos Monoclonales/uso terapéutico , Antivirales/uso terapéutico , COVID-19/terapia , Síndromes de Inmunodeficiencia/terapia , SARS-CoV-2/efectos de los fármacos , Adenosina Monofosfato/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Alanina/uso terapéutico , Linfocitos B/inmunología , Linfocitos B/patología , COVID-19/inmunología , COVID-19/patología , COVID-19/virología , Enfermedad Crónica , Femenino , Humanos , Inmunización Pasiva , Síndromes de Inmunodeficiencia/inmunología , Síndromes de Inmunodeficiencia/patología , Síndromes de Inmunodeficiencia/virología , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Proteínas Recombinantes de Fusión/administración & dosificación , Recurrencia , SARS-CoV-2/patogenicidad , Insuficiencia del Tratamiento , Sueroterapia para COVID-19
3.
Signal Transduct Target Ther ; 6(1): 345, 2021 09 22.
Artículo en Inglés | MEDLINE | ID: mdl-34552055

RESUMEN

The SARS-CoV-2 infection causes severe immune disruption. However, it is unclear if disrupted immune regulation still exists and pertains in recovered COVID-19 patients. In our study, we have characterized the immune phenotype of B cells from 15 recovered COVID-19 patients, and found that healthy controls and recovered patients had similar B-cell populations before and after BCR stimulation, but the frequencies of PBC in patients were significantly increased when compared to healthy controls before stimulation. However, the percentage of unswitched memory B cells was decreased in recovered patients but not changed in healthy controls upon BCR stimulation. Interestingly, we found that CD19 expression was significantly reduced in almost all the B-cell subsets in recovered patients. Moreover, the BCR signaling and early B-cell response were disrupted upon BCR stimulation. Mechanistically, we found that the reduced CD19 expression was caused by the dysregulation of cell metabolism. In conclusion, we found that SARS-CoV-2 infection causes immunodeficiency in recovered patients by downregulating CD19 expression in B cells via enhancing B-cell metabolism, which may provide a new intervention target to cure COVID-19.


Asunto(s)
Antígenos CD19/inmunología , Linfocitos B/inmunología , COVID-19/inmunología , Regulación hacia Abajo/inmunología , Síndromes de Inmunodeficiencia/inmunología , SARS-CoV-2/inmunología , Animales , COVID-19/complicaciones , Chlorocebus aethiops , Femenino , Humanos , Síndromes de Inmunodeficiencia/etiología , Síndromes de Inmunodeficiencia/virología , Memoria Inmunológica , Masculino , Ratones , Ratones Transgénicos , Receptores de Antígenos de Linfocitos B/inmunología , Células Vero
5.
Am J Surg Pathol ; 45(11): 1561-1572, 2021 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-34010154

RESUMEN

Adult-onset immunodeficiency syndrome (AOIS) caused by anti-interferon-γ autoantibodies is an emerging disease. Affected patients present typically with systemic lymphadenopathy, fatigue, and fever. We studied 36 biopsy specimens, 31 lymph nodes, and 5 extranodal sites, of AOIS confirmed by serum autoantibody or QuantiFERON-TB Gold In-Tube assay. We describe the morphologic features and the results of ancillary studies, including special stains, immunohistochemistry, and molecular testing. The overall median age of these patients was 60.5 years (range, 41 to 83 y) with a male-to-female ratio of 20:16. All biopsy specimens showed nontuberculous mycobacterial infection, and most cases showed the following histologic features: capsular thickening with intranodal sclerosing fibrosis, irregularly distributed ill-formed granulomas or histiocytic aggregates with neutrophilic infiltration, interfollicular expansion by a polymorphic infiltrate with some Hodgkin-like cells that commonly effaces most of the nodal architecture and proliferation of high endothelial venules. In situ hybridization analysis for Epstein-Barr virus-encoded RNA showed scattered (<1%) to relatively more common (4% to 5%) positive cells in 29 of 30 (97%) tested specimens, reflecting immune dysregulation due to an interferon-γ defect. In the 31 lymph node specimens, 23 (74%) cases showed increased immunoglobulin G4-positive plasma cells (4 to 145/HPF; mean, 49.7/HPF) with focal areas of sclerosis reminiscent of immunoglobulin G4-related lymphadenopathy, 4 (13%) cases resembled, in part, nodular sclerosis Hodgkin lymphoma, and 9 (29%) cases mimicked T-cell lymphoma. Among 33 patients with available clinical follow-up, 20 (61%) showed persistent or refractory disease despite antimycobacterial therapy, and 1 patient died of the disease. We conclude that the presence of ill-defined granulomas, clusters of neutrophils adjacent to the histiocytic aggregates, and some Epstein-Barr virus-positive cells are features highly suggestive of AOIS. A high index of clinical suspicion and awareness of the morphologic features and differential diagnosis of AOIS are helpful for establishing the diagnosis.


Asunto(s)
Autoanticuerpos/sangre , Síndromes de Inmunodeficiencia/inmunología , Interferón gamma/inmunología , Ganglios Linfáticos/inmunología , Linfadenopatía/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Biopsia , Diagnóstico Diferencial , Femenino , Herpesvirus Humano 4/aislamiento & purificación , Histiocitos/inmunología , Histiocitos/patología , Humanos , Síndromes de Inmunodeficiencia/microbiología , Síndromes de Inmunodeficiencia/patología , Síndromes de Inmunodeficiencia/virología , Ganglios Linfáticos/microbiología , Ganglios Linfáticos/patología , Ganglios Linfáticos/virología , Linfadenopatía/microbiología , Linfadenopatía/patología , Linfadenopatía/virología , Masculino , Persona de Mediana Edad , Neutrófilos/inmunología , Neutrófilos/patología , Micobacterias no Tuberculosas/aislamiento & purificación , Valor Predictivo de las Pruebas , Pronóstico
7.
Nat Med ; 27(1): 28-33, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33442016

RESUMEN

COVID-19, caused by SARS-CoV-2 infection, is mild to moderate in the majority of previously healthy individuals, but can cause life-threatening disease or persistent debilitating symptoms in some cases. The most important determinant of disease severity is age, with individuals over 65 years having the greatest risk of requiring intensive care, and men are more susceptible than women. In contrast to other respiratory viral infections, young children seem to be less severely affected. It is now clear that mild to severe acute infection is not the only outcome of COVID-19, and long-lasting symptoms are also possible. In contrast to severe acute COVID-19, such 'long COVID' is seemingly more likely in women than in men. Also, postinfectious hyperinflammatory disease has been described as an additional outcome after SARS-CoV-2 infection. Here I discuss our current understanding of the immunological determinants of COVID-19 disease presentation and severity and relate this to known immune-system differences between young and old people and between men and women, and other factors associated with different disease presentations and severity.


Asunto(s)
COVID-19/inmunología , COVID-19/fisiopatología , SARS-CoV-2/fisiología , Inmunidad Adaptativa , Adulto , Factores de Edad , Anciano , COVID-19/complicaciones , COVID-19/epidemiología , COVID-19/etiología , Niño , Femenino , Humanos , Inmunidad Innata , Síndromes de Inmunodeficiencia/inducido químicamente , Síndromes de Inmunodeficiencia/inmunología , Síndromes de Inmunodeficiencia/virología , Masculino , SARS-CoV-2/inmunología , Índice de Severidad de la Enfermedad , Factores Sexuales , Síndrome de Respuesta Inflamatoria Sistémica/etiología , Internalización del Virus
8.
J Glob Antimicrob Resist ; 24: 106-107, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33359936

RESUMEN

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a positive-sense single-stranded RNA virus. As of today, no specific treatment has been found COVID-19. Intravenous immunoglobulin (IVIG) is a widely used therapy to prevent life-threatening infections in patients with primary and secondary immune deficiencies and autoimmune/inflammatory conditions. IVIG administration could be beneficial in the treatment of patients with severe COVID-19. In this respect, this presentation aimed to report a case of COVID-19 treated with IVIG.


Asunto(s)
Tratamiento Farmacológico de COVID-19 , Inmunoglobulinas Intravenosas/uso terapéutico , Antivirales/uso terapéutico , COVID-19/diagnóstico por imagen , COVID-19/inmunología , Diabetes Mellitus Tipo 2/inmunología , Diabetes Mellitus Tipo 2/virología , Humanos , Síndromes de Inmunodeficiencia/inmunología , Síndromes de Inmunodeficiencia/virología , Masculino , Persona de Mediana Edad , SARS-CoV-2/aislamiento & purificación
9.
Rev. Hosp. Clin. Univ. Chile ; 32(2): 149-158, 2021.
Artículo en Español | LILACS | ID: biblio-1344247

RESUMEN

SARS-CoV-2 infection in the people has been characterized by great variability in the clinical manifestations, ranging from an asymptomatic infection in some individuals to a fatal disease in others. Recently, the importance of human genetics in determining clinical response has been highlighted. Within this context there are patients who don't become infected despite viral exposure and others who, being young without comorbidities, develop a severe disease.On the other hand, it's under constant investigation whether the presence of a concomitant primary or secondary immunodeficiency determines a different clinical course. (AU)


Asunto(s)
Humanos , Masculino , Femenino , SARS-CoV-2/inmunología , Síndromes de Inmunodeficiencia/inmunología , COVID-19/complicaciones , Síndromes de Inmunodeficiencia/complicaciones , Síndromes de Inmunodeficiencia/genética , Síndromes de Inmunodeficiencia/virología
10.
Transpl Infect Dis ; 22(4): e13301, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32363665

RESUMEN

BACKGROUND: Enterovirus/rhinoviruses (EvRh) are the most common cause of respiratory virus infections in recipients of allogeneic stem cell transplantation (allo-HSCT). OBJECTIVE: We sought to analyze the value of the immunodeficiency scoring index (ISI) in predicting lower respiratory tract disease (LRTD) progression and mortality in a prospective cohort of consecutive adult (>16 years) allo-HSCT recipients with EvRh infection from December 1 2013 to December 1 2019 at two Spanish transplant centers. RESULTS: We included 234 allo-HSCT recipients with 383 EvRh episodes. Out of 383 EvRh episodes, 98 (25%) had LRTD. Multivariate logistic regression analysis identified three independent factors associated with LRTD progression: Ig G < 400 mg/dL, community-acquired respiratory virus (CARV) co-infection and high-risk ISI. Inclusion of Ig G levels and CARV co-infection in the ISI improved its performance by significantly increasing the area under the receiver operator characteristic curve (AUROC) from 0.643 to 0.734 (P = .03). Likewise, the two conditions identified by multivariate analyses as associated with higher probability of mortality were high-risk ISI and EvRh infection within 6 months after transplant. CONCLUSIONS: Our findings confirm the value of high-risk ISI in predicting both probability of EvRh LRTD and 3-month overall mortality. We also demonstrate that the original ISI could be adapted to other CARV types by including additional variables to improve its performance.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/efectos adversos , Síndromes de Inmunodeficiencia/virología , Infecciones por Picornaviridae/inmunología , Infecciones del Sistema Respiratorio/inmunología , Adolescente , Adulto , Anciano , Femenino , Humanos , Síndromes de Inmunodeficiencia/epidemiología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Infecciones por Picornaviridae/mortalidad , Estudios Prospectivos , Curva ROC , Infecciones del Sistema Respiratorio/mortalidad , Infecciones del Sistema Respiratorio/virología , Estudios Retrospectivos , Rhinovirus/inmunología , España/epidemiología , Trasplante Homólogo/efectos adversos , Adulto Joven
11.
Hum Genet ; 139(6-7): 885-901, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32152698

RESUMEN

Epstein-Barr virus (EBV) is a ubiquitous human pathogen, infecting > 90% of the adult population. In the vast majority of healthy individuals, infection with EBV runs a relatively benign course. However, EBV is by no means a benign pathogen. Indeed, apart from being associated with at least seven different types of malignancies, EBV infection can cause severe and often fatal diseases-hemophagocytic lymphohistiocytosis, lymphoproliferative disease, B-cell lymphoma-in rare individuals with specific monogenic inborn errors of immunity. The discovery and detailed investigation of inborn errors of immunity characterized by heightened susceptibility to, or increased frequency of, EBV-induced disease have elegantly revealed cell types and signaling pathways that play critical and non-redundant roles in host-defense against EBV. These analyses have revealed not only mechanisms underlying EBV-induced disease in rare genetic conditions, but also identified molecules and pathways that could be targeted to treat severe EBV infection and pathological consequences in immunodeficient hosts, or even potentially enhance the efficacy of an EBV-specific vaccine.


Asunto(s)
Infecciones por Virus de Epstein-Barr/complicaciones , Predisposición Genética a la Enfermedad , Herpesvirus Humano 4/inmunología , Interacciones Huésped-Patógeno/genética , Síndromes de Inmunodeficiencia/complicaciones , Trastornos Linfoproliferativos/etiología , Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por Virus de Epstein-Barr/virología , Herpesvirus Humano 4/genética , Humanos , Síndromes de Inmunodeficiencia/inmunología , Síndromes de Inmunodeficiencia/virología , Trastornos Linfoproliferativos/patología , Transducción de Señal
12.
Curr Opin Immunol ; 62: 106-122, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-32014647

RESUMEN

Infections with any of the nine human herpes viruses (HHV) can be asymptomatic or life-threatening. The study of patients with severe diseases caused by HHVs, in the absence of overt acquired immunodeficiency, has led to the discovery or diagnosis of various inborn errors of immunity. The related inborn errors of adaptive immunity disrupt α/ß T-cell rather than B-cell immunity. Affected patients typically develop HHV infections in the context of other infectious diseases. However, this is not always the case, as illustrated by inborn errors of SAP-dependent T-cell immunity to EBV-infected B cells. The related inborn errors of innate immunity disrupt leukocytes other than T and B cells, non-hematopoietic cells, or both. Patients typically develop only a single type of infection due to HHV, although, again, this is not always the case, as illustrated by inborn errors of TLR3 immunity resulting in HSV1 encephalitis in some patients and influenza pneumonitis in others. Most severe HHV infections in otherwise healthy patients remains unexplained. The forward human genetic dissection of isolated and syndromic HHV-driven illnesses will establish the molecular and cellular basis of protective immunity to HHVs, paving the way for novel diagnosis and management strategies.


Asunto(s)
Enfermedades Genéticas Congénitas/inmunología , Infecciones por Herpesviridae/inmunología , Herpesviridae/inmunología , Inmunidad Innata/inmunología , Síndromes de Inmunodeficiencia/inmunología , Enfermedades Genéticas Congénitas/diagnóstico , Enfermedades Genéticas Congénitas/virología , Herpesviridae/aislamiento & purificación , Infecciones por Herpesviridae/transmisión , Infecciones por Herpesviridae/virología , Humanos , Síndromes de Inmunodeficiencia/diagnóstico , Síndromes de Inmunodeficiencia/virología
13.
BMC Infect Dis ; 20(1): 80, 2020 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-31992207

RESUMEN

BACKGROUND: In addition to outbreaks of nosocomial influenza, sporadic nosocomial influenza infections also occur but are generally not reported in the literature. This study aimed to determine the epidemiologic characteristics of cases of nosocomial influenza compared with the remaining severe cases of severe influenza in acute hospitals in Catalonia (Spain) which were identified by surveillance. METHODS: An observational case-case epidemiological study was carried out in patients aged ≥18 years from Catalan 12 hospitals between 2010 and 2016. For each laboratory-confirmed influenza case (nosocomial or not) we collected demographic, virological and clinical characteristics. We defined patients with nosocomial influenza as those admitted to a hospital for a reason other than acute respiratory infection in whom ILI symptoms developed ≥48 h after admission and influenza virus infection was confirmed using RT-PCR. Mixed-effects regression was used to estimate the crude and adjusted OR. RESULTS: One thousand seven hundred twenty-two hospitalized patients with severe laboratory-confirmed influenza virus infection were included: 96 (5.6%) were classified as nosocomial influenza and more frequently had > 14 days of hospital stay (42.7% vs. 27.7%, P < .001) and higher mortality (18.8% vs. 12.6%, P < .02). The variables associated with nosocomial influenza cases in acute-care hospital settings were chronic renal disease (aOR 2.44 95% CI 1.44-4.15) and immunodeficiency (aOR 1.79 95% CI 1.04-3.06). CONCLUSIONS: Nosocomial infections are a recurring problem associated with high rates of chronic diseases and death. These findings underline the need for adherence to infection control guidelines.


Asunto(s)
Infección Hospitalaria/epidemiología , Gripe Humana/epidemiología , Adolescente , Adulto , Anciano , Infección Hospitalaria/tratamiento farmacológico , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Síndromes de Inmunodeficiencia/epidemiología , Síndromes de Inmunodeficiencia/virología , Control de Infecciones , Gripe Humana/tratamiento farmacológico , Gripe Humana/virología , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Estaciones del Año , España/epidemiología , Adulto Joven
14.
Epidemiol Infect ; 147: e295, 2019 10 24.
Artículo en Inglés | MEDLINE | ID: mdl-31647050

RESUMEN

Conditions and evidence continue to evolve related to the prediction of the prevalence of immunodeficiency-associated long-term vaccine-derived poliovirus (iVDPV) excreters, which affect assumptions related to forecasting risks and evaluating potential risk management options. Multiple recent reviews provided information about individual iVDPV excreters, but inconsistencies among the reviews raise some challenges. This analysis revisits the available evidence related to iVDPV excreters and provides updated model estimates that can support future risk management decisions. The results suggest that the prevalence of iVDPV excreters remains highly uncertain and variable, but generally confirms the importance of managing the risks associated with iVDPV excreters throughout the polio endgame in the context of successful cessation of all oral poliovirus vaccine use.


Asunto(s)
Síndromes de Inmunodeficiencia/virología , Poliomielitis/prevención & control , Vacunas contra Poliovirus , Esparcimiento de Virus , Antivirales/uso terapéutico , Femenino , Salud Global , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Síndromes de Inmunodeficiencia/tratamiento farmacológico , Síndromes de Inmunodeficiencia/epidemiología , Factores Inmunológicos/uso terapéutico , Masculino , Modelos Inmunológicos , Poliomielitis/tratamiento farmacológico , Poliomielitis/transmisión , Poliomielitis/virología , Prevalencia , Vigilancia en Salud Pública , Medición de Riesgo
15.
Hum Pathol ; 88: 60-65, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30946931

RESUMEN

Epstein-Barr virus (EBV) is associated with many neoplastic hematologic conditions, but scattered EBV-positive cells can be detected in lymph nodes of healthy individuals and they usually represent latently infected lymphocytes. The incidence of EBV detection in normal bone marrow samples has not been studied and is largely unknown. The lack of knowledge regarding the true incidence of encountering bystander latent EBV-positive cells in the bone marrow may potentially lead to a diagnostic dilemma when assessing a staging bone marrow for a patient with an EBV-positive B or T/NK-cell lymphoma. The aim of our study was to investigate the rate of detection of EBV expression in bone marrow samples and correlate any positive findings with various clinical parameters including patient's age, sex, clinical history, immune status, and any neoplastic transformation if follow-up data are available. We retrospectively studied 230 consecutive bone marrow biopsies performed in 2013 and found 5 cases (2.17%) with scattered EBV-positive cells by in situ hybridization. The observed scattered EBV-positive cells are largely small in size and likely represent bystander, latently infected cells. The rate of detection of EBV-positive cells in the bone marrow appears to be slightly higher in immunodeficient individuals (3%) than in immunocompetent patients (1%).


Asunto(s)
Células de la Médula Ósea/virología , Herpesvirus Humano 4/aislamiento & purificación , Adulto , Anciano , Biopsia , Médula Ósea/patología , Células de la Médula Ósea/patología , Etnicidad , Femenino , Humanos , Síndromes de Inmunodeficiencia/virología , Hibridación in Situ , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
16.
Clin Infect Dis ; 68(10): 1750-1753, 2019 05 02.
Artículo en Inglés | MEDLINE | ID: mdl-30689814

RESUMEN

We enrolled 427 human immunodeficiency virus-infected children (median age, 7.3 years), 59.2% severely immunodeficient, with suspected tuberculosis in Southeast Asian and African settings. Nontuberculous mycobacteria were isolated in 46 children (10.8%); 45.7% of isolates were Mycobacterium avium complex. Southeast Asian origin, age 5-9 years, and severe immunodeficiency were independently associated with nontuberculous mycobacteria isolation. CLINICAL TRIALS REGISTRATION: NCT01331811.


Asunto(s)
Infecciones por VIH/complicaciones , Síndromes de Inmunodeficiencia/epidemiología , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Micobacterias no Tuberculosas/aislamiento & purificación , Tuberculosis/epidemiología , África/epidemiología , Asia Sudoriental/epidemiología , Niño , Preescolar , Técnicas de Laboratorio Clínico , VIH , Infecciones por VIH/epidemiología , Infecciones por VIH/microbiología , Humanos , Síndromes de Inmunodeficiencia/microbiología , Síndromes de Inmunodeficiencia/virología , Infecciones por Mycobacterium no Tuberculosas/epidemiología , Infecciones por Mycobacterium no Tuberculosas/microbiología , Complejo Mycobacterium avium/aislamiento & purificación , Micobacterias no Tuberculosas/clasificación , Estudios Prospectivos , Tuberculosis/diagnóstico , Tuberculosis/microbiología
17.
J Clin Immunol ; 39(1): 112-117, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30680653

RESUMEN

PURPOSE: Nitazoxanide was recently reported as having in vitro effectiveness against the rubella virus. Immunodeficiency-related vaccine-derived rubella occurs in some patients who have an inherited immunodeficiency and who received the MMR vaccine. This study investigated the in vivo effectiveness of nitazoxanide therapy. METHODS: This is a retrospective analysis of seven patients treated with nitazoxanide as salvage therapy for immunodeficiency-related vaccine-derived rubella infection. The patients were recruited from an ongoing rubella detection surveillance project. RESULTS: Seven patients with persistent rubella were treated with nitazoxanide and one demonstrated significant clinical improvement. Two additional patients exhibited diminished viral capsid production with one patient having transient slowing of progression. The cohort overall generally had low T cell counts and had a high burden of comorbidities. There were three deaths. Two deaths were from PML and one was related to hematopoietic stem cell transplantation. CONCLUSIONS: Nitazoxanide has limited in vivo anti-viral effects for immunodeficiency-related vaccine-derived rubella. Most patients did not exhibit clinical improvement.


Asunto(s)
Granuloma/tratamiento farmacológico , Síndromes de Inmunodeficiencia/virología , Virus de la Rubéola/efectos de los fármacos , Rubéola (Sarampión Alemán)/tratamiento farmacológico , Tiazoles/uso terapéutico , Adolescente , Niño , Preescolar , Femenino , Granuloma/virología , Humanos , Lactante , Masculino , Nitrocompuestos , Estudios Retrospectivos , Rubéola (Sarampión Alemán)/virología , Linfocitos T/efectos de los fármacos , Linfocitos T/virología , Vacunación/métodos
18.
FEMS Microbiol Rev ; 43(2): 181-192, 2019 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-30649299

RESUMEN

Human γ-herpesviruses include the closely related tumor viruses Epstein Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV). EBV is the most growth-transforming pathogen known and is linked to at least seven human malignancies. KSHV is also associated with three human cancers. Most EBV- and KSHV-infected individuals fortunately remain disease-free despite persistent infection and this is likely due to the robustness of the immune control that they mount against these tumor viruses. However, upon immune suppression EBV- and KSHV-associated malignancies emerge at increased frequencies. Moreover, primary immunodeficiencies with individual mutations that predispose to EBV or KSHV disease allow us to gain insights into a catalog of molecules that are required for the immune control of these tumor viruses. Curiously, there is little overlap between the mutation targets that predispose individuals to EBV versus KSHV disease, even so both viruses can infect the same host cell, human B cells. These differences will be discussed in this review. A better understanding of the crucial components in the near-perfect life-long immune control of EBV and KSHV should allow us to target malignancies that are associated with these viruses, but also induce similar immune responses against other tumors.


Asunto(s)
Herpesviridae/inmunología , Interacciones Huésped-Patógeno/inmunología , Síndromes de Inmunodeficiencia/virología , Neoplasias/virología , Virus Oncogénicos/inmunología , Predisposición Genética a la Enfermedad , Herpesvirus Humano 4/inmunología , Herpesvirus Humano 8/inmunología , Humanos , Inmunocompetencia/genética
19.
J Clin Immunol ; 39(1): 81-89, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30607663

RESUMEN

The association of immunodeficiency-related vaccine-derived rubella virus (iVDRV) with cutaneous and visceral granulomatous disease has been reported in patients with primary immunodeficiency disorders (PIDs). The majority of these PID patients with rubella-positive granulomas had DNA repair disorders. To support this line of inquiry, we provide additional descriptive data on seven previously reported patients with Nijmegen breakage syndrome (NBS) (n = 3) and ataxia telangiectasia (AT) (n = 4) as well as eight previously unreported patients with iVDRV-induced cutaneous granulomas and DNA repair disorders including NBS (n = 1), AT (n = 5), DNA ligase 4 deficiency (n = 1), and Artemis deficiency (n = 1). We also provide descriptive data on several previously unreported PID patients with iVDRV-induced cutaneous granulomas including cartilage hair hypoplasia (n = 1), warts, hypogammaglobulinemia, immunodeficiency, myelokathexis (WHIM) syndrome (n = 1), MHC class II deficiency (n = 1), Coronin-1A deficiency (n = 1), X-linked severe combined immunodeficiency (X-SCID) (n = 1), and combined immunodeficiency without a molecular diagnosis (n = 1). At the time of this report, the median age of the patients with skin granulomas and DNA repair disorders was 9 years (range 3-18). Cutaneous granulomas have been documented in all, while visceral granulomas were observed in six cases (40%). All patients had received rubella virus vaccine. The median duration of time elapsed from vaccination to the development of cutaneous granulomas was 48 months (range 2-152). Hematopoietic cell transplantation was reported to result in scarring resolution of cutaneous granulomas in two patients with NBS, one patient with AT, one patient with Artemis deficiency, one patient with DNA Ligase 4 deficiency, one patient with MHC class II deficiency, and one patient with combined immunodeficiency without a known molecular etiology. Of the previously reported and unreported cases, the majority share the diagnosis of a DNA repair disorder. Analysis of additional patients with this complication may clarify determinants of rubella pathogenesis, identify specific immune defects resulting in chronic infection, and may lead to defect-specific therapies.


Asunto(s)
Reparación del ADN/genética , Granuloma/complicaciones , Granuloma/virología , Síndromes de Inmunodeficiencia/complicaciones , Virus de la Rubéola/patogenicidad , Enfermedades de la Piel/etiología , Enfermedades de la Piel/virología , Adolescente , Ataxia Telangiectasia/genética , Ataxia Telangiectasia/virología , Niño , Preescolar , Femenino , Granuloma/genética , Cabello/anomalías , Cabello/virología , Trasplante de Células Madre Hematopoyéticas/métodos , Enfermedad de Hirschsprung/genética , Enfermedad de Hirschsprung/virología , Humanos , Síndromes de Inmunodeficiencia/genética , Síndromes de Inmunodeficiencia/virología , Masculino , Síndrome de Nijmegen/genética , Síndrome de Nijmegen/virología , Osteocondrodisplasias/congénito , Osteocondrodisplasias/genética , Osteocondrodisplasias/virología , Enfermedades de Inmunodeficiencia Primaria , Rubéola (Sarampión Alemán)/genética , Rubéola (Sarampión Alemán)/virología , Piel/virología , Enfermedades de la Piel/genética , Enfermedades por Inmunodeficiencia Combinada Ligada al Cromosoma X/genética , Enfermedades por Inmunodeficiencia Combinada Ligada al Cromosoma X/virología
20.
Diagn Microbiol Infect Dis ; 93(1): 69-73, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30174143

RESUMEN

OBJECTIVE: Predictive factors associated with clinical outcomes of chronic norovirus infection (CNI) in primary immunodeficiency diseases (PIDD) are lacking. METHOD: We sought to characterize CNI using a multi-institutional cohort of patients with PIDD and CNI using the Clinical Immunology Society's CIS-PIDD Listserv e-mail group. RESULTS: Thirty-four subjects (21 males and 13 females) were reported from centers across North America, Europe, and Asia. All subjects were receiving high doses (median IgG dose: 1200 mg/kg/month) of supplemental immunoglobulin therapy. Fifty-three percent had a complete absence of B cells (median B-cell count 0; range 0-139 cells/µL). Common Variable Immune Deficiency (CVID) subjects manifested a unique phenotype with B-cell lymphopenia, non O+ blood type, and villous atrophy (logistic regression model, P = 0.01). Five subjects died, all of whom had no evidence of villous atrophy. CONCLUSION: While Norovirus (NoV) is thought to replicate in B cells, in this PIDD cohort of CNI, B-cell lymphopenia was common, indicating that the presence of B lymphocytes is not essential for CNI.


Asunto(s)
Infecciones por Caliciviridae/inmunología , Síndromes de Inmunodeficiencia/virología , Norovirus/fisiología , Adolescente , Adulto , Linfocitos B/patología , Infecciones por Caliciviridae/mortalidad , Infecciones por Caliciviridae/patología , Enfermedad Crónica , Inmunodeficiencia Variable Común/inmunología , Inmunodeficiencia Variable Común/patología , Inmunodeficiencia Variable Común/terapia , Inmunodeficiencia Variable Común/virología , Femenino , Gastroenteritis/inmunología , Gastroenteritis/mortalidad , Gastroenteritis/patología , Humanos , Inmunización Pasiva , Síndromes de Inmunodeficiencia/inmunología , Síndromes de Inmunodeficiencia/patología , Síndromes de Inmunodeficiencia/terapia , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Norovirus/genética , Estudios Retrospectivos , Adulto Joven
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA