Andrés Felipe Zea-Vera

Purpose The SAP-SLAM receptor system plays a critical role in immune regulation, with SAP deficiency leading to apoptosis resistance in T cells and disrupting immune homeostasis, as seen in XLP-1. This disorder, characterized by uncontrolled lymphoproliferation, often presents with a variable clinical spectrum. Methods We report a case of XLP-1 with dysgammaglobulinemia in a patient initially diagnosed with pediatric-onset CVID. Through quantitative and functional analysis of the SH2D1A c.164G > A (p.Arg55Gln) variant, we confirmed its pathogenicity. Results Our findings demonstrate that this variant significantly impairs B cell differentiation and proliferation independently of T cell interactions Conclusion These results support the pathogenic nature of SH2D1A R55Q and advocate for its reclassification as a pathogenic mutation.

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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%).

Se trata de un paciente de sexo masculino de 45 años con tos persistente de cuatro meses de duración, acompañada de fiebre y una significativa pérdida de peso.En la tomografía de tórax, se observó una neumonía idiopática y los estudios posteriores identificaron una carga viral positiva para citomegalovirus (CMV) en el lavado broncoalveolar. La biopsia transbronquial confirmó inclusiones basófilas intranucleares indicativas de la infección por CMV. Los valores de las inmunoglobulinas fueron: IgA < 0,13, IgG < 3 e IgM < 0,25 g/L. La biopsia de médula ósea reveló un aumento del 80 % en el número de células, sin alteraciones morfológicas. Se indicaron estudios complementarios para la agammaglobulinemia.

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 theirhealthcare 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.

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 exomesequencing 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.