RESUMEN
BACKGROUND: Common Variable Immunodeficiency (CVID) is a heterogeneous disorder characterized by defective B cell differentiation and antibody production. Interleukin (IL)-21 activates STAT3, a potent regulator of B cell differentiation into plasma cells. We have studied the phosphorylation of STAT3 in CVID patients and its contribution to B cells subsets. METHODS: We studied 23 CVID patients and 14 healthy donors (HD), determining pSTAT3 in naïve and memory B cells, stimulated with IL-21 at 15 and 60 min. RESULTS: pSTAT3 was increased in total (p = 0.044), naïve (p = 0.023), and memory (p = 0.001) B cells at 60 min in CVID patients compared with HD. We classified patients by the percentage of isotype-switched memory B cells. We observed an increase in pSTAT3 at 60 min in memory B cells in both CVID groups of patients (p = 0.026, p = 0.007, respectively). Interestingly, the analysis of each group individually; demonstrated that patients with decreased memory B cells exhibited an increase in pSTAT3 at 60 min (p = 0.023), while HD had an expected decrease in pSTAT3 (p = 0.045). CONCLUSION: CVID patients showed an increased atypical of pSTAT3, which could affect the differentiation of B cells. Further studies in the IL-21 pathway are necessary to understand how this alteration could promote differentiation defects in patient B cells.
Asunto(s)
Subgrupos de Linfocitos B , Inmunodeficiencia Variable Común , Linfocitos B , Inmunodeficiencia Variable Común/metabolismo , Humanos , Activación de Linfocitos , Fosforilación , Factor de Transcripción STAT3/metabolismoRESUMEN
PURPOSE: Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by an inability of phagocytes to produce reactive oxygen species, impairing their killing of various bacteria and fungi. We summarize here the 93 cases of CGD diagnosed in Mexico from 2011 to 2019. METHODS: Thirteen Mexican hospitals participated in this study. We describe the genetic, immunological, and clinical features of the 93 CGD patients from 78 unrelated kindreds. RESULTS: Eighty-two of the patients (88%) were male. All patients developed bacterial infections and 30% suffered from some kind of fungal infection. Fifty-four BCG-vaccinated patients (58%) presented infectious complications of BCG vaccine. Tuberculosis occurred in 29%. Granulomas were found in 56% of the patients. Autoimmune and inflammatory diseases were present in 15% of patients. A biological diagnosis of CGD was made in 89/93 patients, on the basis of NBT assay (n = 6), DHR (n = 27), and NBT plus DHR (n = 56). The deficiency was complete in all patients. The median age of biological diagnosis was 17 months (range, 0-186 months). A genetic diagnosis was made in 83/93 patients (when material was available), corresponding to CYBB (n = 64), NCF1 (n = 7), NCF2 (n = 7), and CYBA (n = 5) mutations. CONCLUSIONS: The clinical manifestations in these Mexican CGD patients were similar to those in patients elsewhere. This cohort is the largest in Latin America. Mycobacterial infections are an important cause of morbidity in Mexico, as in other countries in which tuberculosis is endemic and infants are vaccinated with BCG. X-linked CGD accounted for most of the cases in Mexico, as in other Latin American countries. However, a significant number of CYBA and NCF2 mutations were identified, expanding the spectrum of known causal mutations.
Asunto(s)
Enfermedad Granulomatosa Crónica/inmunología , Mutación/genética , Infecciones por Mycobacterium/epidemiología , Mycobacterium/fisiología , NADPH Oxidasa 2/genética , NADPH Oxidasas/genética , Adolescente , Autoinmunidad , Niño , Preescolar , Estudios de Cohortes , Femenino , Genes Ligados a X , Enfermedad Granulomatosa Crónica/epidemiología , Enfermedad Granulomatosa Crónica/genética , Humanos , Lactante , Recién Nacido , Inflamación , Masculino , México/epidemiologíaRESUMEN
Hyper IgE syndrome (HIES) is characterized by recurrent skin abscesses, eczema, pneumonia, and high levels of serum IgE. Nonimmunologic manifestations of HIES include a characteristic face, pathologic dentition, scoliosis, bone alterations, hyperextensible joints, and vascular abnormalities. Somatic mosaicism is defined by the presence of two or more populations of cells with different genotypes in one individual. In this report, we describe one patient with classical HIES and another patient with a mild phenotype, both harboring the same genetic mutation. The patient with a mild phenotype did not present the characteristic face, had normal production of IL-17A by T CD4+ cells, but had low phosphorylation of STAT-3 in B cells. Interestingly, the mutation found in B cells was absent in other cell types analyzed, in agreement with the presence of a somatic mosaic genotype. The clinical and functional differences observed between these patients justify the use of complementary tools for a better definition of the cases. These approaches allow for a better understanding of complex phenotypes associated with somatic mosaicisms, and present the possibility to analyze the role of B lymphocytes in the pathophysiology of this disease. This knowledge has an impact on not only the treatment but also the provision of appropriate genetic counseling.
Asunto(s)
Linfocitos B/fisiología , Síndrome de Job/inmunología , Mosaicismo , Mutación/genética , Factor de Transcripción STAT3/genética , Células Th17/fisiología , Adulto , Células Cultivadas , Femenino , Asesoramiento Genético , Genotipo , Humanos , Inmunoglobulina E/metabolismo , Memoria Inmunológica , Interleucina-17/metabolismo , Síndrome de Job/diagnóstico , Masculino , Especificidad de Órganos , Fenotipo , Fosforilación/genética , Factor de Transcripción STAT3/metabolismo , Adulto JovenRESUMEN
Hyper-IgM (HIGM) syndrome is a heterogeneous group of disorders characterized by normal or elevated serum IgM levels associated with absent or decreased IgG, IgA and IgE. Here we summarize data from the HIGM syndrome Registry of the Latin American Society for Immunodeficiencies (LASID). Of the 58 patients from 51 families reported to the registry with the clinical phenotype of HIGM syndrome, molecular defects were identified in 37 patients thus far. We retrospectively analyzed the clinical, immunological and molecular data from these 37 patients. CD40 ligand (CD40L) deficiency was found in 35 patients from 25 families and activation-induced cytidine deaminase (AID) deficiency in 2 unrelated patients. Five previously unreported mutations were identified in the CD40L gene (CD40LG). Respiratory tract infections, mainly pneumonia, were the most frequent clinical manifestation. Previously undescribed fungal and opportunistic infections were observed in CD40L-deficient patients but not in the two patients with AID deficiency. These include the first cases of pneumonia caused by Mycoplasma pneumoniae, Serratia marcescens or Aspergillus sp. and diarrhea caused by Microsporidium sp. or Isospora belli. Except for four CD40L-deficient patients who died from complications of presumptive central nervous system infections or sepsis, all patients reported in this study are alive. Four CD40L-deficient patients underwent successful bone marrow transplantation. This report characterizes the clinical and genetic spectrum of HIGM syndrome in Latin America and expands the understanding of the genotype and phenotype of this syndrome in tropical areas.
Asunto(s)
Síndrome de Inmunodeficiencia con Hiper-IgM/epidemiología , Ligando de CD40/deficiencia , Ligando de CD40/genética , Preescolar , Comorbilidad , Citidina Desaminasa/deficiencia , Citidina Desaminasa/genética , Femenino , Hispánicos o Latinos , Humanos , Síndrome de Inmunodeficiencia con Hiper-IgM/complicaciones , Síndrome de Inmunodeficiencia con Hiper-IgM/diagnóstico , Síndrome de Inmunodeficiencia con Hiper-IgM/terapia , Lactante , Recién Nacido , Infecciones/diagnóstico , Infecciones/etiología , Pulmón/patología , Masculino , Sistema de Registros , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
Kawasaki disease is an acute febrile multisystemic vasculitis affecting children that can affect the coronary arteries. Routine BCG vaccination in Mexico leads to a 99% coverage in infants younger than 1 year. We present a case of Kawasaki disease with skin lesions at the site of BCG. Clinicians should be aware of this clinical manifestation that could help diagnose atypical or incomplete cases of the disease.
Asunto(s)
Anticuerpos Antibacterianos/inmunología , Vacuna BCG , Cicatriz/inmunología , Síndrome Mucocutáneo Linfonodular/inmunología , Mycobacterium bovis/inmunología , Enfermedades Cutáneas Papuloescamosas/etiología , Aspirina/uso terapéutico , Reacciones Cruzadas , Humanos , Hidrocortisona/uso terapéutico , Inmunoglobulinas Intravenosas/uso terapéutico , Memoria Inmunológica , Lactante , Masculino , Síndrome Mucocutáneo Linfonodular/complicaciones , Prednisona/uso terapéutico , Enfermedades Cutáneas Papuloescamosas/tratamiento farmacológico , Enfermedades Cutáneas Papuloescamosas/inmunologíaRESUMEN
Churg-Strauss syndrome (CSS) is one of the rarest forms of vasculitis, and very rarely presents in the pediatric population. We present two cases of childhood CSS, both with hepatic and cardiac involvement. To our knowledge, these are the first two cases of CSS in the pediatric population described in Mexico.