Sara Elva Espinosa-Padilla

Instituto Nacional de Pediatría, Ciudad de México, The Federal District, Mexico

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Publications (16)39.85 Total impact

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    ABSTRACT: Severe combined immunodeficiency (SCID) is a syndrome characterized by profound T-cell deficiency. BCG vaccine is contraindicated in patients with SCID. Because most countries encourage BCG vaccination at birth, a high percentage of patients with SCID are vaccinated before their immune defect is detected. We sought to describe the complications and risks associated with BCG vaccination in patients with SCID. An extensive standardized questionnaire evaluating complications, therapeutics, and outcomes regarding BCG vaccination in patients given a diagnosis of SCID was widely distributed. Summary statistics and association analysis was performed. Data on 349 BCG-vaccinated patients with SCID from 28 centers in 17 countries were analyzed. Fifty-one percent of the patients had BCG-associated complications, 34% disseminated and 17% localized (a 33,000- and 400-fold increase, respectively, over the general population). Patients receiving early vaccination (≤1 month) showed an increased prevalence of complications (P = .006) and death caused by BCG-associated complications (P < .0001). The odds of experiencing complications among patients with T-cell numbers of 250/μL or less at diagnosis was 2.1 times higher (95% CI, 1.4-3.4 times higher; P = .001) than among those with T-cell numbers of greater than 250/μL. BCG-associated complications were reported in 2 of 78 patients who received antimycobacterial therapy while asymptomatic, and no deaths caused by BCG-associated complications occurred in this group. In contrast, 46 BCG-associated deaths were reported among 160 patients treated with antimycobacterial therapy for a symptomatic BCG infection (P < .0001). BCG vaccine has a very high rate of complications in patients with SCID, which increase morbidity and mortality rates. Until safer and more efficient antituberculosis vaccines become available, delay in BCG vaccination should be considered to protect highly vulnerable populations from preventable complications.
    The Journal of allergy and clinical immunology 04/2014; 133(4):1134-41. · 12.05 Impact Factor
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    ABSTRACT: Autosomal recessive IFN-γR2 deficiency is a rare genetic etiology of Mendelian susceptibility to mycobacterial diseases (MSMD). We and others previously characterized the molecular basis of disease in patients with complete deficiency, including four patients with residual cell surface expression of non-functional receptors (homozygous for mutations T168N and 382-387dup). We herein report the molecular investigation of two previously reported patients with partial IFN-γR2 deficiency (R114C and G227R), and three novel, unrelated children (P1, P2 and P3). P1 is homozygous for the S124F IFNGR2 mutation, whereas P2 and P3 are homozygous for G141R. IFN-γR2 levels on the surface of the three patients' cells are slightly lower than those on control cells. The patients' cells also display impaired, but not abolished, response to IFN-γ, which is improved by transfection of the wild-type IFNGR2 allele. Moreover, the R114C, S124F, G141R and G227R IFNGR2 hypomorphic alleles all encode misfolded proteins with abnormal N-glycosylation. The mutants are largely retained in the endoplasmic reticulum, although a small proportion reach and function at the cell surface. Strikingly, the IFN-γ response of the patients' cells is enhanced by chemical modifiers of N-glycosylation, as previously shown for patients with gain-of-glysosylation T168N and misfolding 382-387dup null mutations. All four in-frame IFNGR2 hypomorphic mutant alleles encoding surface-expressed receptors are thus deleterious by a mechanism involving abnormal N-glycosylation and misfolding of the IFN-γR2 protein, which can be rescued by inhibitors of glycosylation. The diagnosis of partial IFN-γR2 deficiency is clinically useful, as affected patients should be treated with IFN-γ, unlike patients with complete IFN-γR2 deficiency. Moreover, inhibitors of glycosylation might be beneficial in patients with complete or partial IFN-γR2 deficiency due to misfolding or gain-of-glycosylation receptors.
    Blood 08/2013; · 9.06 Impact Factor
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    ABSTRACT: Streptococcus pneumoniae infection continues to be a major source of morbidity and mortality in children in Mexico. The aim of this study was to evaluate the immune response to six serotypes in children <5 years of age after immunization with a 23-valent pneumococcal polysaccharide vaccine. A prospective study was conducted among children aged from 18 months to 4 years. Pre- and postvaccination titers for the serotypes selected in this project demonstrate a substantial response among all age groups. We identified mild adverse events in 62% of the participants in this study. No serious adverse events were reported during the study. Pneumococcal polysaccharide vaccine produced adequate immunogenicity in all age groups evaluated.
    Archives of medical research 08/2012; 43(5):402-5. · 1.88 Impact Factor
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    ABSTRACT: To evaluate the lipopolysaccharide (LPS)-induced pro-inflammatory cytokine response by peripheral blood mononuclear cells (PBMCs) from XLA patients. Thirteen patients with XLA were included in the study. LPS-induced TNF-α, IL-1β, IL-6, and IL-10 production was determined in PBMCs from patients and matched healthy controls by ELISA. Cytokine production was correlated with the severity of mutation, affected domain and clinical characteristics. In response to LPS, PBMCs from XLA patients produced significantly higher amounts of pro-inflammatory cytokines and IL-10 compared to controls, and this production was influenced neither by the severity of the mutation nor the affected domain. PBMCs from patients with a history of more hospital admissions before their diagnosis produced higher levels of TNF-α. PBMCs from patients with lower serum IgA levels showed a higher production of TNF-α and IL-1β. Less severe (punctual) mutations in the Btk gene were associated with higher serum IgG levels at diagnosis. Our results demonstrate a predominantly inflammatory response in XLA patients after LPS stimulation and suggest a deregulation of TLR signaling in the absence of Btk. This response may be influenced by environmental factors.
    Journal of Clinical Immunology 06/2012; 32(5):967-74. · 3.38 Impact Factor
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    ABSTRACT: The absence of an appropriate central tolerance in primary immunodeficiencies favors proliferation of autoreactive lymphocyte clones, causing a greater incidence of autoimmunity. Del 22q11.2 syndrome presents an increased incidence of allergic and autoimmune diseases. One of the most relevant and frequent immune manifestations is autoimmune thrombocytopenia. We present the case of a pediatric patient with autoimmune thrombocytopenia due to the immunological dysregulation observed in partial DiGeorge syndrome.
    Journal of Pediatric Hematology/Oncology 08/2011; 33(6):465-6. · 0.97 Impact Factor
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    ABSTRACT: RESUMEN La enfermedad granulomatosa crónica es una inmunodeficiencia primaria, específicamente un defecto de la fagocitosis. Aparece en 1 de cada 200,000 nacimientos y es producida por mutaciones en los genes que codifican para la enzima nicotinamida adenina dinucleótido fosfato oxidasa (NADPH oxidasa). La forma de herencia es ligada al cromosoma X (>60%) o autosómica recesiva (30 a 40%). La NADPH oxidasa produce radicales libres de oxígeno en los fagocitos activados ("estallido respiratorio"). Al haber mutaciones de los genes de la NADPH oxidasa no se producen radicales libres y, en consecuencia, los neutrófilos de pacientes con enfermedad granulomatosa crónica son incapaces de destruir a los patógenos fagocitados. Estos pacientes son especialmente susceptibles a infecciones por estafilococos, hongos y algunas bacterias gramnegativas. Las principales manifestaciones clínicas son cuadros recurrentes y graves de linfadenitis, neumonías, osteomielitis, formación de granulomas y sepsis. El diagnóstico se establece por el antecedente de infecciones recurrentes, casos familiares, falla para medrar, y se confirma con resultados alterados en la prueba e producción de radicales libres de oxígeno y la mutación específica. El tratamiento consiste en trasplante de células progenitoras hematopoyéticas. El diagnóstico temprano y el tratamiento con antibióticos profilácticos e interferón gamma modifican favorablemente la morbilidad y mortalidad en estos pacientes. Palabras clave: enfermedad granulomatosa crónica, NADPH, infecciones recurrentes.
    Revista Alergia México. 01/2009; 56:165-74.
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    ABSTRACT: RESUMEN La enfermedad granulomatosa crónica es una inmunodeficiencia primaria, específicamente un defecto de la fagocitosis. Aparece en 1 de cada 200,000 nacimientos y es producida por mutaciones en los genes que codifican para la enzima nicotinamida adenina dinucleótido fosfato oxidasa (NADPH oxidasa). La forma de herencia es ligada al cromosoma X (>60%) o autosómica recesiva (30 a 40%). La NADPH oxidasa produce radicales libres de oxígeno en los fagocitos activados ("estallido respiratorio"). Al haber mutaciones de los genes de la NADPH oxidasa no se producen radicales libres y, en consecuencia, los neutrófilos de pacientes con enfermedad granulomatosa crónica son incapaces de destruir a los patógenos fagocitados. Estos pacientes son especialmente susceptibles a infecciones por estafilococos, hongos y algunas bacterias gramnegativas. Las principales manifestaciones clínicas son cuadros recurrentes y graves de linfadenitis, neumonías, osteomielitis, formación de granulomas y sepsis. El diagnóstico se establece por el antecedente de infecciones recurrentes, casos familiares, falla para medrar, y se confirma con resultados alterados en la prueba e producción de radicales libres de oxígeno y la mutación específica. El tratamiento consiste en trasplante de células progenitoras hematopoyéticas. El diagnóstico temprano y el tratamiento con antibióticos profilácticos e interferón gamma modifican favorablemente la morbilidad y mortalidad en estos pacientes. Palabras clave: enfermedad granulomatosa crónica, NADPH, infecciones recurrentes.
    Revista Alergia México Volume Revista Alergia México. 01/2009; 5656:162-70.
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    ABSTRACT: Chronic granulomatous disease (CGD) is a primary immunodeficiency, a phagocyte defect that appears in 1:200,000 live births and is produced by mutations in the genes that codify for the enzyme nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase). The inheritance form is X linked (> 60%) or autosomic recesive (30-40%). The NADPH oxidase is responsible for the production of reactive oxygen species (ROS) in the activated phagocyte ("respiratory burst"). When present, mutations on the NAPDH oxidase genes do not allow the ROS production, making the neutrophils of these patients incapable to destroy pathogens. These patients are especially susceptible to infections by staphylococcus, fungi and some gram-negative bacteria. The main clinical manifestations include recurrent life-threatening episodes of lymphadenitis, abscess, pneumonias, osteomyelitis, granuloma formation and sepsis. The diagnosis is suggested by a history of recurrent infections, familiar cases, fail to grow and confirmed with an altered test of ROS production and the specific mutation. Allogenic stem cells transplant is the curative treatment. The early diagnosis and the treatment with prophylactic antibiotics and interferon-gamma have modified favorably the morbidity and mortality of these patients.
    Alergia 01/2009; 56(5):165-74.
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    ABSTRACT: This is the second report on the continuing efforts of LAGID to increase the recognition and registration of patients with primary immunodeficiency diseases in 12 Latin American countries: Argentina, Brazil, Chile, Colombia, Costa Rica, Honduras, Mexico, Panama, Paraguay, Peru, Uruguay, and Venezuela. This report reveals that from a total of 3321 patients registered, the most common form of primary immunodeficiency disease was predominantly antibody deficiency (53.2%) with IgA deficiency reported as the most frequent phenotype. This category was followed by 22.6% other well-defined ID syndromes, 9.5% combined T- and B-cell inmunodeficiency, 8.6% phagocytic disorders, 3.3% diseases of immune dysregulation, and 2.8% complement deficiencies. All countries that participated in the first publication in 1998 reported an increase in registered primary immunodeficiency cases, ranging between 10 and 80%. A comparison of the estimated minimal incidence of X-linked agammaglobulinemia, chronic granulomatous disease, and severe combined immunodeficiency between the first report and the present one shows an increase in the reporting of these diseases in all countries. In this report, the estimated minimal incidence of chronic granulomatous disease was between 0.72 and 1.26 cases per 100,000 births in Argentina, Chile, Costa Rica, and Uruguay and the incidence of severe combined immunodeficiency was 1.28 and 3.79 per 100,000 births in Chile and Costa Rica, respectively. However, these diseases are underreported in other participating countries. In addition to a better diagnosis of primary immunodeficiency diseases, more work on improving the registration of patients by each participating country and by countries that have not yet joined LAGID is still needed.
    Journal of Clinical Immunology 02/2007; 27(1):101-8. · 3.38 Impact Factor
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    ABSTRACT: Hyper-IgE syndrome (HIES) is a primary immunodeficiency characterized by recurrent skin abscesses, recurrent pneumonia with pneumatocele formation, eczema, eosinophilia, and elevated levels of serum IgE. Patients with the autosomal recessive (AR) form of HIES appear to be prone to developing autoimmune diseases. We present two cases of HIES with autoimmune complications; one case was a product of a consanguineous marriage, the other one was a sporadic case. The first patient presented with recurrent episodes of erythema nodosum, warts, bronchiolitis obliterans and thrombocytopenia. The second patient developed glomerulonephritis resulting in endstage renal failure. She later developed malar rash, oral ulcers, cerebral infarcts with vasculitis and positive ANA, anti-dsDNA, and antiphospholipid antibodies. We discuss the dilemma in treating patients who present with both primary immunodeficiency and autoimmunity.
    Pediatric Nephrology 09/2006; 21(8):1200-5. · 2.94 Impact Factor
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    ABSTRACT: Juvenile Polyarteritis nodosa (PAN) and Kawasaki Disease (KD) are disseminated vasculitides of unknown cause affecting small- and medium-sized vessels in children. We present an unusually severe case that fulfilled criteria for both KD and PAN. The diagnosis, overlapping clinical features, and treatment options for the 2 diseases are discussed. A 3-year-old girl with systemic vasculitis is presented. We compare our case to 4 other cases reported in the literature which presented with a similar diagnostic dilemma. A review of the medical literature and a qualitative analysis of the diseases were performed, with emphasis on overlapping features, atypical cases, and treatment options. Many features of KD and PAN are shared; however, there are some clinical features that could help differentiate one from the other. Fever, weight loss, rash, abdominal pain, arthritis, coronary arteritis, peripheral gangrene, anemia, leukocytosis, thrombocytosis, and elevated C-reactive protein are among many of the features that are shared by both diseases. However, KD also has unique clinical features that include conjunctivitis, changes in the lips and mouth, desquamation of the fingertips, and gallbladder hydrops, whereas renal involvement in KD is rare. Occasionally juvenile PAN and KD share clinical manifestations, and when they do, it may be impossible to differentiate between them. Treatment should be directed according to the severity and persistence of these clinical manifestations.
    Seminars in Arthritis and Rheumatism 07/2006; 35(6):349-54. · 3.81 Impact Factor
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    ABSTRACT: 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.
    Pediatric Pulmonology 05/2006; 41(4):379-82. · 2.38 Impact Factor
  • Journal of Allergy and Clinical Immunology - J ALLERG CLIN IMMUNOL. 01/2005; 115(2).
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    ABSTRACT: Common variable immunodeficiency (CVID) is one of the most common antibody deficiencies, is characterized by low serum immunoglobulins, defective antibody response and increased susceptibility to chronic and recurrent infections. we present the clinical findings of patients with CVID in two hospitals in Mexico City. We performed a retrospective study of patients who filled CVID criteria. We collected the following information, demographic data, age at onset, age at diagnosis, family history, infection, autoimmunity, lymphoproliferative disease, allergy, malignancy, immunoglobulin levels at diagnosis, route of administration, dosage and frequency of IVIG of each patient. Data were analyzed with descriptive statistics. Amongst 26 patients who filled CVID criteria, 14 were men and 12 women. The mean diagnosis delay was 48 months (22-128), serum immunoglobulins at diagnosis in mg/dL were IgG 216 (114-316), IgM 21 (12-121), IgA 21 (6-26) and IgE 4.6 (1.8) IU/mL. 81% of patients suffered pneumonia. There was a decrease in the number of pneumonias before and after treatment with gammaglobulin (p = 0.028). 27% of the patients had autoimmune diseases, 35% allergies, 35% chronic diarrhea, 62% bronchiectasis, 73% chronic cough, 50% lymphadenopathy. One patient had lymphoproliferative disease and none developed malignancy. We found that the delay in the diagnosis and initiation of gammaglobulin replacement affects the occurrence of complications such as bronchiectasis.
    Alergia 60(1):26-30.
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    ABSTRACT: The transfer factor (TF) was described in 1955 by S. Lawrence. In 1992 Kirkpatrick characterized the specific TF at molecular level. The TF is constituted by a group of numerous molecules, of low molecular weight, from 1.0 to 6.0 kDa. The 5 kDa fraction corresponds to the TF specific to antigens. There are a number of publications about the clinical indications of the TF for diverse diseases, in particular those where the cellular immune response is compromised or in those where there is a deficient regulation of the immune response. In this article we present our clinical and basic experiences, especially regarding the indications, usage and dosage of the TF. Our group demonstrated that the TF increases the expression of IFN-gamma and RANTES, while decreases the expression of osteopontine. Using animal models we have worked with M. tuberculosis, and with a model of glioma with good therapeutic results. In the clinical setting we have worked with herpes zoster, herpes simplex type I, herpetic keratitis, atopic dermatitis, osteosarcoma, tuberculosis, asthma, post-herpetic neuritis, anergic coccidioidomycosis, leishmaniasis, toxoplasmosis, mucocutaneous candidiasis, pediatric infections produced by diverse pathogen germs, sinusitis, pharyngitis, and otits media. All of these diseases were studied through protocols which main goals were to study the therapeutic effects of the TF, and to establish in a systematic way diverse dosage schema and time for treatment to guide the prescription of the TF.
    Alergia 54(4):134-9.