Inborn errors of immunity is a diverse group of rare diseases caused by over 400 genetic mutations affecting the immune system and increasing infection susceptibility, autoimmunity, and malignancy. Hematopoietic stem cell transplantation offers a curative option for some inborn errors of immunity, with haploidentical donors providing a viable alternative when identical donors are unavailable.

Inborn errors of immunity are monogenic disorders that predispose patients to immune dysregulation, autoimmunity, and infection. Some autoimmune diseases, such as autoimmune cytopenias, systemic lupus erythematosus, and inflammatory bowel diseases, are increasingly recognized as phenotypes of inborn errors of immunity. The objective of this article was to identify red flags or clinical/laboratory markers to suspect inborn errors of immunity in patients with autoimmune cytopenias, systemic lupus erythematosus, and inflammatory bowel diseases through a systematic literature review. The study followed the systematic reviews and meta-analysis guidelines (PRISMA). After selection, we included 36 articles, and their methodological quality was verified using the Joanna Briggs Institute tools for individual risk of bias analysis. The principal red flags in autoimmune cytopenias are chronic, recurrent, and refractory cytopenias, recurrent infection, severe infectious complications associated with immunosuppressive treatment, and chronic lymphoproliferation. In systemic lupus erythematosus, red flags include age of onset before five years, severe organ involvement, chilblain lesions, and chronic lymphoproliferation. For inflammatory bowel diseases, red flags are an age of onset before two years, resistance to conventional therapies, atypical endoscopic or histologic findings, and consanguineous parents. Autoimmune diseases may be the primary manifestation of inborn errors of immunity in pediatric and adult patients. An early diagnosis of a monogenic disorder allows for the tailoring of effective treatment plans, providing prognostic information to families, and offering genetic counseling.

Chronic granulomatous disease is the inborn error of immunity with the highest frequency of invasive aspergillosis. In this context, invasive aspergillosis is frequent in adolescence, with rare cases before one year of age. We present a case of chronic granulomatous disease and invasive aspergillosis in a four-month-old infant. The patient was a male infant living in jail with his hypothyroid mother. He presented with a tumor in the left axillary region when he was four months old, and the chest X-ray suggested rib fractures. The patient was hospitalized on suspicion of child abuse. The chest computed tomography scan showed axillary abscess, rib osteolysis, pneumonia, and pulmonary nodules. He was treated with broad-spectrum antibiotics, and then he was discharged. Four months later, he was readmitted with fever and extension of the purulent abscess to the left scapular region; a computed tomography scan showed worsening images. Aspergillus fumigatus was isolated from the abscess pus, leading to an invasive aspergillosis diagnosis. The patient was treated with voriconazole for 28 days, and then he was discharged. The chronic granulomatous disease was diagnosed by the dihydrorhodamine test. The mutated gene causing the inborn error of immunity was CYBB with the variant c.80_83del/Y; the mother was the carrier (c.80_83del/WT). At 12 months of age, the patient was readmitted for invasive aspergillosis, refractory to treatment, and died. This exceptional case teaches us how environmental conditions determine exposure to infectious agents in chronic granulomatous disease patients. Also, it illustrates that invasive aspergillosis can develope in infants with this pathology and should be treated aggressively.

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.

Autoimmune responses are characterized by the development of antibodies and the activation of T lymphocytes against self-antigens. This leads to an effector immune response against tissues expressing antigens, which are later recognized by the host immune system. Host antigens attacked by antibodies are called "autoantigens" and are of different kinds, including receptors, enzymes, and channel proteins. The autoimmune response is potentiated by cytokines that mediate the activation of Th1, Th2, or Th17 lymphocytes. The released cytokines can also be recognized as autoantigens, meaning they can be targets of the autoimmune response. The effects of autoimmunity on cytokines or their receptors are diverse, and the mechanisms of this type of autoimmune response are discussed in this review.

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.

STAT1 is a cytoplasmic transcription factor associated with cell growth regulation, differentiation, proliferation, metabolism, and apoptosis. IFN-mediated JAK/STAT signaling pathway is involved in eliminating intracellular pathogens and viruses. However, pathogenic variants in STAT1 can result in impaired or increased function. Increased activity or function in STAT1 was described in 2011 and is characterized by excessive phosphorylation of the transcription factor. Carriers can develop autoimmune and inflammatory diseases and are susceptible to fungal, viral, and bacterial infections. The early and common manifestation is chronic mucocutaneous candidiasis. Here, we report a clinical case of a patient with increased STAT1 activity or gain of function, which started in the first year of his life. He is currently 27 years old and has presented bacillus Calmette-Guérin and Mycobacterium tuberculosis infection, chronic mucocutaneous candidiasis, tinea capitis, and facial and ocular rosacea. HIV infection was ruled out. Given the clinical manifestations, an inborn error of immunity was suspected, specifically STAT1 with gain of function. The diagnosis was corroborated by the sequencing of multiple genes associated with inborn errors of immunity. The pathogenic variant c.961A>G (p.Arg321Gly) in the STAT1 gene, previously reported as a gain of function mutation, was found in the patient. Finally, this case illustrates that mutations in immune-associated genes can contribute to producing severe and recurrent infections, even in adult patients. Chronic mucocutaneous candidiasis should raise suspicion of gain of function in STAT1.

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.

Chronic granulomatous disease is a defect in phagocytosis due to deficiency of gp91phox, p22phox, p47phox, p40phox, and p67phox (classic form of the disease). Recently, EROS and p40phox deficiency were described as responsible for the non-classical form of the disease. The 1,2,3-dihydrorhodamine oxidation technique, with phorbol-12-myristate-13-acetate as a stimulus, is performed to diagnose the classic chronic granulomatous disease. However, oxidation mediated by EROS and p40phox requires stimuli such as zymosan, Escherichia coli, or Staphylococcus aureus.

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.

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.

In this manuscript, we carried out an exhaustive analysis of the global recommendations for immunization in inborn errors of immunity patients. We examined the mechanisms of action and types of vaccines, and we described the vaccines included in the Colombian immunization program together with the specific guidelines for immunization in patients with the most frequent inborn errors of immunity in Colombia. These recommendations were adjusted according to the severity and subclassifications of each immunodeficiency, considering variations in the immune response to offer evidencebased recommendations for vaccination in children with these conditions. We included the most common inborn errors of immunity worldwide and considered the vaccines included in the Colombian immunization program to avoid delays in vaccination schedules. This work was achieved through a narrative, non-systematic review of articles indexed in Spanish and English, using MeSH terms such as: “inborn errors of immunity”, “primary immunodeficiencies”, “vaccination in inborn errors of immunity, “types of vaccines”, “mechanism of action of vaccines”, and “live vaccines in inborn errors of immunity”. We used search engines such as: PubMed, Medline, ScienceDirect, and websites of recognized institutions such as the Centers for Disease Control and Prevention (CDC).

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. Specific antibody deficiency is an innate error of humoral immunity characterized by normal levels of immunoglobulin isotypes, recurrent infections, and a reduced reaction to polysaccharide antigens in vaccines. Objective. To describe the clinical and immunological characteristics of patients with specific antibody deficiency attending a pediatric hospital in Bogotá between May 2021 and September 2023. Materials and methods. We reviewed the medical records of 16 patients with specific antibody deficiency. Results. The median age at diagnosis was six and a half years. Nine were male, and 7 had a history of prematurity. Eleven patients had adequate nutritional status, and 7 had standard height. The most frequent recurrent infection was pneumonia, affecting 12 patients; more than half of them experienced some associated complications. The most common phenotype was moderate, and 15 of the individuals received immunoglobulin as definitive treatment. Conclusion. Specific antibody deficiency is a frequently underdiagnosed functional alteration of the immune system. It should be suspected in patients experiencing recurrent otitis media and pneumonia or in cases complicated by septic shock, pleural effusion, or necrotizing pneumonia.

A 45-year-old male patient presented with a persistent cough lasting four months, accompanied by fever and significant weight loss. A chest computed tomography revealed cryptogenic pneumonia, and subsequent investigations identified a positive cytomegalovirus (CMV) viral load in bronchoalveolar lavage. A transbronchial biopsy confirmed intranuclear basophilic inclusions indicative of CMV infection. Additionally, blood tests returned positive results for CMV. Immunoglobulin levels revealed IgA < 0.13, IgG < 3, IgM < 0.25 (g/L). Bone marrow biopsy indicated an 80% hypercellularity without morphological alterations. Additional studies for agammaglobulinemia were asked for.

Psoriatic arthritis is a complex disease, and human leukocyte antigens (HLA) are key to its development. Latin America and, specifically, Colombia, has scarce data about patients with psoriatic arthritis.

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 the patients. 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.

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.

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.

Immunodeficiencies are disturbances in the immune system that can affect cell function, quantity, or both. They can be either primary, associated with genetic defects, or secondary, linked to external factors such as hemato-oncological conditions. Secondary immunodeficiencies can lead to the initiation, reactivation, or acceleration of latent, residual, or active infections, which are the leading cause of mortality.

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