Biomedica : revista del Instituto Nacional de Salud最新文献

Activated phosphoinositide 3-kinase δ syndrome is an inborn error of immunity due to mutations within the genes responsible for encoding PI3Kδ subunits. This syndrome results in an excessive activation of the phosphoinositide 3-kinase signaling pathway. Gainof-function mutations in the gene PIK3R1 (encoding p85α, p55α, and p50α) lead to the development of the activated PI3K δ syndrome. Notably, the clinical presentations of this syndrome often closely resemble those of other primary immunodeficiencies. We present a case involving a 15-year-old male who displayed an immunological phenotype that bore a striking resemblance to hyper-IgM syndrome. Whole exome sequencing was undertaken to pinpoint the underlying genetic mutation. Our investigation successfully identified a heterozygous splice site mutation previously reported within the well-established hotspot of the PIK3R1 gene (GRCh37, c.1425+1 G>T). The diverse spectrum of inborn errors of immunity underscores the pivotal role of identifying gene mutations, particularly in patients presenting clinical manifestations spanning autoimmune disorders, lymphoproliferative conditions, and antibody deficiencies. Such precise genetic diagnoses hold significant potential for improving patient care and management.

Introduction: Inborn errors of immunity include a broad spectrum of genetic diseases, in which a specific gene mutation might alter the entire emphasis and approach for an individual patient.

Objective: To conduct a comprehensive analysis of the correlation between phenotypic and molecular diagnoses in patients with confirmed inborn errors of immunity at a tertiary hospital in Cali, Colombia.

Materials and methods: We conducted a retrospective study in which we sequentially evaluated all available institutional medical records with a diagnosis of inborn errors of immunity.

Results: In the Clinical Immunology Service of the Hospital Universitario del Valle, 517 patients were evaluated. According to the IUIS-2022 classification, 92 patients (17.35%) were definitively diagnosed with an inborn error of immunity. Of these, 38 patients underwent genetic studies. The most prevalent category was predominantly antibody deficiencies (group III) (38/92 - 41.3%). A broad spectrum of genetic defects, novel and previously reported, were described, including mutations in the following genes: ATM, BTK, ERBIN, MAB21L2, RAG2, SAVI, SH2D1A, STAT1, SYK, and TMEM173. Less frequent findings included cases of the WHIM syndrome, SYK gain-of-function, and IL-7 deficiency.

Conclusions: The establishment of the Clinical Immunology Service in the Hospital Universitario del Valle has emerged as a pivotal resource, catering to individuals with limited financial means and covered by public health insurance within the southwest region of Colombia. Molecular genetics confirmatory diagnosis was achieved in 38 patients (41.3%) with inborn errors of immunity and changed the diagnosis in 24 cases (26%).

Introduction. Hemophagocytic syndrome is an under-recognized condition with high mortality in the pediatric population. It is characterized by excessive activation of immune cells and cytokine release, leading to persistent inflammation. Hemophagocytic syndrome can be primary or secondary and associated with different triggers.Objective. To describe 12 clinical cases of children under five years of age with hemophagocytic syndrome in a high-complexity institution in southwestern Colombia.Materials and methods. We present a retrospective series of 12 cases of hemophagocytic syndrome in children under five years of age treated at a high-complexity institution in Colombia between 2019 and 2022.Results. The median age of the patients was one year and 7 were male. Fever and splenomegaly were the most common clinical manifestations observed in 11 of thepatients. The predominant laboratory findings included hyperferritinemia (n = 11), hypertriglyceridemia (n = 10), bicytopenia (n = 6), and pancytopenia (n = 2). Eleven cases had elevated lactate dehydrogenase levels. Genetic studies were conducted in 7 patients. Regarding treatment, the full HLH-2004 protocol was administered to 5 cases, while 3 underwent hematopoietic stem cell transplantation. Three patients died.Conclusion. We highlight the complexity of the hemophagocytic syndrome, especially in children under five years old, because the low prevalence and non-specific clinical presentation of the disease contribute to its underdiagnosis. Emphasis is placed on identifying triggers, performing genetic evaluation for accurate and early diagnosis, adopting a multidisciplinary approach, and considering early hematopoietic stem cell transplantation to improve morbidity and mortality outcomes.

Introduction: Congenital lymphopenias cause increased susceptibility to infections in children apparently healthy at birth. Earlier detection of these conditions would facilitate prompt treatment, prevent potentially serious disease complications and early deaths, and save healthcare resources.

Objective: To perform a pilot study for neonatal screening of congenital lymphopenias by the quantification of TREC and KREC –T- and B-cell receptor excision circles– in peripheral blood samples from newborns in Medellín, Colombia.

Materials and methods: Blood samples from 1,092 newborns and six referred patients with suspected lymphopenia were collected by heel or toe-finger prick and dropped onto a filter paper. Thereafter, DNA was extracted and levels of TRECs and KRECs were measured by qPCR.

Results: The six patients with suspected lymphopenia showed undetectable or very low TREC levels. All newborns screened presented normal TREC and KREC levels. A positive correlation was found between TREC or KREC values quantified from two different filter papers. Detectable levels of the receptor excision circles decrease considerably after 24 weeks of the dried blood spot sample storage. We identified a positive association between low TREC levels and low birth weight; and a negative correlation between KREC values and prematurity. Finally, no statistical differences were found between TREC or KREC levels and delivery method.

Conclusion: We describe the first preliminary study for the early detection of lymphopenias in Colombia. We proposed to use a cut-off value of 119 and 69 copies/μl blood of TREC and KREC, respectively for future newborn screening programs in our country.

Introduction: Graft-versus-host disease is a serious complication after hematopoietic stem cell transplantation and is a major cause of death post-transplantation. Approximately 50% of acute graft-versus-host disease patients do not respond to systemic steroids and their prognosis is poor regardless of the treatment. This study describes our experience with pediatric patients diagnosed with steroid-refractory graft-versus-host disease who received intra-mesenteric steroid treatment.

Objective: To determine the outcomes of intra-mesenteric steroid use in the management of pediatric patients diagnosed with refractory graft-versus-host disease.

Materials and methods: The study included patients under 18 years old with allogeneic hematopoietic stem cell transplantation who underwent intra-mesenteric steroid injection for resistant gastrointestinal graft-versus-host disease between January, 2016, and December, 2021. Methylprednisolone was administered via intra-arterial injection through the celiac trunk and the superior and inferior mesenteric arteries.

Results: We collected data on 21 patients: nine (90%) responded with a subjective decrease in fecal output and a reduction in bilirubin and transaminases. Seven patients required a second intra-mesenteric injection and presented a complete response in 85% of the cases. Only one patient experienced local complications after the procedure. Twelve patients (57%) died with one death due to acute graft-versus-host disease.

Conclusion: Reports in the adult population have shown an approximately 50% response rate with few complications, making it a second-line management standard. As far as we know, this is the largest pediatric cohort reported in Latin America. Our findings suggest that intra-mesenteric steroid administration for managing hepatic and gastrointestinal graftversus-host disease may be considered an early adjuvant treatment in patients with steroidrefractory graft-versus-host disease.

Introduction: Chronic granulomatous disease is a congenital immune disorder characterized by increased susceptibility to fungal and bacterial infections and dysregulated inflammation. It is caused by defects in the NADPH oxidase and EROS protein.

Objective: To characterize clinically and genetically four patients with chronic granulomatous disease at the Hospital Infantil de México Federico Gómez.

Materials and methods: Patients diagnosed with chronic granulomatous disease by the dihydrorhodamine oxidase technique were molecularly and genetically characterized by measuring NADPH oxidase subunit expression and exome sequencing and analysis. The different clinical variables were obtained from clinical files, and each case was described.

Results: We described four male patients with chronic granulomatous disease: two with pathogenic variants in CYBB, one with CYBB and adjacent genes deleted, and one without p47phox expression. Mothers of the three patients with mutated CYBB were carriers. All three cases with CYBB had severe and recurrent infections in addition to Calmette-Guérin bacillus infection as the initial manifestation. The autosomal recessive case of p47phox deficiency had the mildest clinical presentation. Deleting CYBB and several contiguous genes was associated with a poor prognosis. None of the patients received hematopoietic stem cell transplantation.

Conclusions: Chronic granulomatous disease, secondary to pathogenic variants in CYBB was the most common in these Mexican patients. The carrier mothers should befollowed clinically because of the potential risk of inflammatory, autoimmune, and infectious manifestations. One of the first manifestations was Calmette-Guérin bacillus infection, and in countries such as Mexico, where this vaccine is administered, cases with any type of adverse reaction should be evaluated to rule out chronic granulomatous disease.

Introduction. Inborn errors of immunity are frequently associated with bronchiectasis. The diagnostic performance of these inborn errors has improved because the association of some of these entities with progressive airway damage is better known. This knowledge has allowed recognition and appropriate intervention reducing deterioration of the pulmonary function and improving quality of life.Objective. To describe a group of patients with bronchiectasis not related to cystic fibrosis who were diagnosed with inborn errors of immunity and have been studied in an immunology reference center in Colombia.Materials and methods. We conducted an observational, descriptive, and retrospective study with participating patients under 18 years, diagnosed with inborn errors of immunity and non-cystic fibrosis bronchiectasis, between December 2013 and December 2023 at the Fundación Valle del Lili in Cali, Colombia.Results. Seventeen patients were diagnosed with non-cystic fibrosis bronchiectasis and inborn errors of immunity. Their mean age was nine years. The lower pulmonary lobe was the most frequently affected segment, and in most cases, unilaterally. The most prevalent alteration was predominantly antibody inmunodeficiency, followed by combined immunodeficiencies associated with syndromes. Thirteen patients had humoral immunity compromise, while 4 exhibited humoral and cellular immunity alterations. Additionally, 12 patients presented genetic mutations related to their phenotype. Thirteen patients, underwent supplementation with intravenous immunoglobulin, and 3 died.Conclusion. The inborn errors of immunity most frequently associated with noncystic fibrosis bronchiectasis, were predominantly antibody deficiency and combined immunodeficiencies with syndromic features.

Introduction: Non-cystic fibrosis bronchiectasis is a complex medical condition with multiple etiologies, characterized by chronic productive cough and radiologic evidence of airway lumen dilation and wall thickening. Associated exacerbations and declining lung function contribute to increasing disability and mortality. There are no data about the prevalence of non-cystic fibrosis bronchiectasis etiologies in the Colombian population.

Objective: To investigate non-cystic fibrosis bronchiectasis etiology and clinical characteristics in adults evaluated in the southwest of Colombia.

Materials and methods: We conducted a cross-sectional, non-interventional study. Subjects diagnosed with non-cystic fibrosis bronchiectasis were referred to by their healthcare providers and then enrolled between October 2018 and April 2021. Medical records and radiological studies were evaluated. Participants underwent laboratory tests, including complete blood count, serum immunoglobulin levels, and, in some cases, additional tests.

Results: We included 161 subjects. The average age was 50 years old, and 59% were females. Bronchiectasis etiology was identified in 84.6% of the cases. Postinfectious (34.6%) and immune disorders (25.3%), represented by autoimmunity (13.6%) and immunodeficiency (11.7%), were the leading causes. Gender differences were noted in autoimmune (females: 18.8% versus males: 6.1%, p = 0.021) and immunodeficiency-related bronchiectasis (males: 21.2% versus females 5.2%, p = 0.002). Immunodeficiencies-associated bronchiectases were more frequent in subjects under 50 years of age, while chronic obstructive pulmonary disease-associated bronchiectases were common in subjects over 50 years of age.

Discussion: The etiologies of non-cystic fibrosis bronchiectasis in Colombia are diverse, exhibiting notable differences from other global regions. Serum immunoglobulin levels and clinical immunologist consultation should be prioritized in diagnosing patients with unclear bronchiectasis etiology, particularly those with recurrent sinopulmonary infections.

Cernunnos/XLF deficiency is a rare, severe combined immunodeficiency, inherited in an autosomal recessive pattern (OMIM number: 611290), related to the NHEJ1 gene. This gene participates in the DNA non-homologous end-joining pathway, repairing double-strand breaks in the DNA of mammalian cells. The clinical features include growth retardation, microcephaly, triangle-shaped face, recurrent infections, fibroblast's excessive sensitivity to gamma-ionizing radiation, and hypogammaglobulinemia; also, low counts of subpopulations of B and T lymphocytes, with normal values of natural-killer cells. This manuscript aims to present an extremely rare case of combined immunodeficiency in a twenty-years-old man with non-consanguineous parents and a homozygote variant of the NHEJ1 gene. This case is the fiftieth reported in the literature and the first in Colombia, given the low prevalence of NHEJ1-related immunodeficiency and its difficult diagnosis due to scarce knowledge.

Introduction: Predominant antibody deficiency is the most frequent group of innate immunity errors, but information about patients’ nutritional status is scarce.

Objectives: To characterize the nutritional status of Colombian patients with predominant antibody deficiencies.

Material and methods: Material and methods. We analyzed medical charts of patients with predominant antibody deficiency in a pediatric hospital in Bogotá.

Results: We analyzed 55 medical charts. The most frequent diagnoses were specific deficiencies of polysaccharide antibodies and immunoglobulin A, common variableimmunodeficiency, and agammaglobulinemia. More than 70% of the patients had sinopulmonary infections, with pneumonia being the most frequent, followed by otitis andsinusitis. In children under five years, 45% had adequate weight for their height, 18% had a risk of malnutrition, and 18% had moderate acute malnutrition. Four-point-five percent had obesity, 4.5% showed overweight, and 9% had a risk of being overweight. Of those older than five years, 54% had an adequate body mass index, 22.5% showed overweight, 9.6% were at risk of thinness, and 9.6% were thin. We found that the risk of short stature and short stature per se were more frequent than the expected height in these patients. The percentages of patients with short stature were higher than those reported nationally.

Conclusions: Due to the epidemic of childhood obesity, it will be more frequent to find overweight or obesity in children above five years. Therefore, finding short stature could be a more sensitive alarm sign for predominant antibody deficiency.