The Latin American Society for Immunodeficiencies Registry.

Purpose - The Latin American Society of Immunodeficiencies (LASID) Registry was established in 2009 to collect data on Inborn Errors of Immunity (IEI) patients in the region. Although several reports have been published regarding LASID data, this is the first report of the entire dataset. Methods - The European Society of Immunodeficiencies (ESID) donated the online platform in 2008. Data was collected from participating centers from Apr 13, 2009, to Dec 31, 2022, and included demographic, clinical, and follow-up information. Results - A total of 9307 patients were included in the database. At the end of the study period, 8,805 patients were alive or lost to follow-up, and 502 were deceased. The most common type of IEI was predominantly antibody deficiency (PAD, 60.35%), and selective IgA deficiency was the most frequent diagnosis (1627 patients, 17.48%), followed by Common Variable Immune Deficiency (CVID, 1191 patients). Most patients (78.16%) were ≤ 18 years old at inclusion, and the median age at diagnosis was 4.77 years. The median time to diagnosis was 5.04 years. Antibiotics were prescribed in 32.3% of visits, followed by immunoglobulins (29.49% ). Hematopoietic stem cell transplantation was performed in 5.03% of patients. Omenn syndrome was the most common disease in deceased patients, with a mortality rate of 52.63%. Conclusion - This study contributes to our understanding of IEIs in Latin America and highlights the importance of early diagnosis, appropriate treatments, and improved data collection to optimize patient outcome.

Latin American consensus on the supportive management of patients with severe combined immunodeficiency.

Severe combined immunodeficiency (SCID) represents the most lethal form of primary immunodeficiency, with mortality rates of greater than 90% within the first year of life without treatment. Hematopoietic stem cell transplantation and gene therapy are the only curative treatments available, and the best-known prognostic factors for success are age at diagnosis, age at hematopoietic stem cell transplantation, and the comorbidities that develop in between. There are no evidence-based guidelines for standardized clinical care for patients with SCID during the time between diagnosis and definitive treatment, and we aim to generate a consensus management strategy on the supportive care of patients with SCID. First, we gathered available information about SCID diagnostic and therapeutic guidelines, then we developed a document including diagnostic and therapeutic interventions, and finally we submitted the interventions for expert consensus through a modified Delphi technique. Interventions are grouped in 10 topic domains, including 123 "agreed" and 38 "nonagreed" statements. This document intends to standardize supportive clinical care of patients with SCID from diagnosis to definitive treatment, reduce disease burden, and ultimately improve prognosis, particularly in countries where newborn screening for SCID is not universally available and delayed diagnosis is the rule. Our work intends to provide a tool not only for immunologists but also for primary care physicians and other specialists involved in the care of patients with SCID.

Attending to warning signs of primary immunodeficiency diseases across the range of clinical practice.

PURPOSE: Patients with primary immunodeficiency diseases (PIDD) may present with recurrent infections affecting different organs, organ-specific inflammation/autoimmunity, and also increased cancer risk, particularly hematopoietic malignancies. The diversity of PIDD and the wide age range over which these clinical occurrences become apparent often make the identification of patients difficult for physicians other than immunologists. The aim of this report is to develop a tool for educative programs targeted to specialists and applied by clinical immunologists. METHODS: Considering the data from national surveys and clinical reports of experiences with specific PIDD patients, an evidence-based list of symptoms, signs, and corresponding laboratory tests were elaborated to help physicians other than immunologists look for PIDD. RESULTS: Tables including main clinical manifestations, restricted immunological evaluation, and possible related diagnosis were organized for general practitioners and 5 specialties. Tables include information on specific warning signs of PIDD for pulmonologists, gastroenterologists, dermatologists, hematologists, and infectious disease specialists. CONCLUSIONS: This report provides clinical immunologists with an instrument they can use to introduce specialists in other areas of medicine to the warning signs of PIDD and increase early diagnosis. Educational programs should be developed attending the needs of each specialty.

Infections With Enterohepatic Non-H. pylori Helicobacter Species in X-Linked Agammaglobulinemia: Clinical Cases and Review of the Literature.

The genus Helicobacter is classified into two main groups according to its habitat: gastric and enterohepatic. Patients with X-linked agammaglobulinemia (XLA) appear to be associated with invasive infection with enterohepatic non-Helicobacter pylori species (NHPH), mainly H. cinaedi and H. bilis. Such infections are difficult to control and have a high potential for recurrence. The spectrum of illnesses caused by these species includes recurrent fever, bacteremia, arthritis, osteomyelitis, cellulitis, abdominal abscesses, and pyoderma gangrenosum-like ulcer. The presence of these Helicobacters is particularly difficult to diagnose and eradicate, as they are very fastidious bacteria and present resistance to several types of antibiotics. We report two clinical cases of XLA patients infected with H. bilis. These infections were chronic in these patients and could not be eradicated in one of them. We also review the cases of enterohepatic non-Helicobacter pylori species (NHPH) in patients with this inborn error of immunity.

Proteomics: a tool to develop novel diagnostic methods and unravel molecular mechanisms of pediatric diseases.

Proteomics is the study of the expression of changes and post-translational modifications (PTM) of proteins along a metabolic condition either normal or pathological. In the field of health, proteomics allows obtaining valuable data for treatment, diagnosis or pathophysiological mechanisms of different illnesses. To illustrate the aforementioned, we describe two projects currently being performed at the Instituto Nacional de Pediatría: The immuno-proteomic study of cow milk allergy and the Proteomic study of childhood cataract. Cow's milk proteins (CMP) are the first antigens to which infants are exposed and generate allergy in some of them. In Mexico, the incidence of CMP allergy has been estimated at 5-7%. Clinical manifestations include both gastrointestinal and extra-gastrointestinal symptoms, making its diagnosis extremely difficult. An inappropriate diagnosis affects the development and growth of children. The goals of the study are to identify the main immune-reactive CMP in Mexican pediatric population and to design more accurate diagnostic tools for this disease. Childhood cataract is a major ocular disease representing one of the main causes of blindness in infants; in developing countries, this disease promotes up to 27% of cases related to visual loss. From this group, it has been estimated that close to 60% of children do not survive beyond two years after vision lost. PTM have been pointed out as the main cause of protein precipitation at the crystalline and, consequently, clouding of this tissue. The study of childhood cataract represents an outstanding opportunity to identify the PTM associated to the cataract-genesis process.

A novel CD40LG deletion causes the hyper-IgM syndrome with normal CD40L expression in a 6-month-old child.

The X-linked hyper-IgM syndrome (XHIGM) is the most common form of HIGM. Patients are clinically diagnosed on the basis of recurrent sinopulmonary infections, accompanied with low levels of IgG and IgA, normal to elevated levels of IgM, and the presence of peripheral B cells. Here, we have reported a novel deletion of four nucleotides in CD40LG exon 3, c.375_378delCAAA, which led to a frameshift mutation with a premature stop codon, p.Asn101*126. The deletion resulted in a truncated protein, in which majority of the extracellular domain was lost. However, detection of surface CD40L was still possible as the intracellular, transmembrane, and part of the extracellular domains were not affected. This indicated that this mutation did not affect protein stability and that immunodetection of CD40L expression is not enough for the diagnosis of XHIGM. Our study strongly suggests that genetic diagnosis for XHIGM should always be performed when clinical data support this diagnosis and CD40L protein is present.

Advances in primary immunodeficiency diseases in Latin America: epidemiology, research, and perspectives.

Primary immunodeficiencies (PIDs) are genetic disorders of the immune system comprising many different phenotypes. Although previously considered rare, recent advances in their clinical, epidemiological, and molecular definitions are revealing how much we still need to learn about them. For example, geographical and ethnic variations as well as the impact of certain practices influence their frequency and presentation, making it necessary to consider their study in terms of regions. The Latin American Society for Immunodeficiencies was established as an organization dedicated to provide scientific support for basic and clinical research and to develop tools and educational resources to promote awareness in the medical community. Initiatives such as these are positively influencing the way PIDs are tackled in these countries, as shown by recent reports and publications. This paper provides a historical compilation and a current view of the many issues faced by scientists studying these diseases in these countries, highlighting the diverse scientific contributions and offering a promising perspective for the further developments in this field in Latin America.

Immunogenicity of a 23-valent pneumococcal polysaccharide vaccine among Mexican children.

BACKGROUND AND AIMS: 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. METHODS: 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. RESULTS: We identified mild adverse events in 62% of the participants in this study. No serious adverse events were reported during the study. CONCLUSIONS: Pneumococcal polysaccharide vaccine produced adequate immunogenicity in all age groups evaluated.

Proteomics: a tool to develop novel diagnostic methods and unravel molecular mechanisms of pediatric diseases / Proteómica: una herramienta para desarrollar nuevos métodos de diagnóstico y descifrar mecanismos moleculares de enfermedades pediátricas

Abstract: Proteomics is the study of the expression of changes and post-translational modifications (PTM) of proteins along a metabolic condition either normal or pathological. In the field of health, proteomics allows obtaining valuable data for treatment, diagnosis or pathophysiological mechanisms of different illnesses. To illustrate the aforementioned, we describe two projects currently being performed at the Instituto Nacional de Pediatría: The immuno-proteomic study of cow milk allergy and the Proteomic study of childhood cataract. Cow's milk proteins (CMP) are the first antigens to which infants are exposed and generate allergy in some of them. In Mexico, the incidence of CMP allergy has been estimated at 5-7%. Clinical manifestations include both gastrointestinal and extra-gastrointestinal symptoms, making its diagnosis extremely difficult. An inappropriate diagnosis affects the development and growth of children. The goals of the study are to identify the main immune-reactive CMP in Mexican pediatric population and to design more accurate diagnostic tools for this disease. Childhood cataract is a major ocular disease representing one of the main causes of blindness in infants; in developing countries, this disease promotes up to 27% of cases related to visual loss. From this group, it has been estimated that close to 60% of children do not survive beyond two years after vision lost. PTM have been pointed out as the main cause of protein precipitation at the crystalline and, consequently, clouding of this tissue. The study of childhood cataract represents an outstanding opportunity to identify the PTM associated to the cataract-genesis process.

Resumen: La proteómica estudia los cambios de expresión y post-traduccionales (PTM) de las proteínas durante una condición metabólica normal o patológica. En el campo de la salud, la proteómica permite obtener datos útiles para el tratamiento, diagnóstico o en la fisiopatología de diferentes enfermedades. Para ilustrar lo anterior, describimos dos proyectos realizados en el Instituto Nacional de Pediatría: El estudio inmunoproteómico de la alergia a la leche y el estudio proteómico de la catarata infantil. Las proteínas de leche bovina (PLB) son los primeros antígenos a los que se exponen los infantes y un porcentaje de ellos generará alergias. En México, se estima que la incidencia de alergias a las PLB es del 5-7%. Las manifestaciones clínicas incluyen tanto síntomas gastrointestinales como extra-gastrointestinales, dificultando su diagnóstico. Un mal diagnóstico afecta el desarrollo y crecimiento del infante. Los objetivos del estudio son identificar las principales PLB inmunoreactivas en población infantil mexicana y diseñar herramientas diagnósticas más precisas para esta patología. La catarata infantil es una enfermedad ocular que representa una de las causas principales de ceguera infantil; en países subdesarrollados genera cerca del 27% de casos relacionados con pérdida visual. De este grupo, se estima que cerca del 60% de los infantes no sobreviven más allá de los dos años después de perder la visión. Se señala a las PTM como las responsables de la precipitación de proteínas del cristalino y, por tanto, de su opacidad. El estudio de la catarata infantil representa una oportunidad para identificar las PTM vinculadas con la cataratogénesis.

Primary immunodeficiency diseases in Latin America: the second report of the LAGID registry.

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.

Dermatomiositis juvenil: perfil clínico en niños mexicanos / Juvenile dermatomyositis. Clinical profile in Mexican children

Objetivo. Conocer el perfil clínico de pacientes pediátricos con dermatomiositis juvenil (DMJ), en función del tiempo de evolución de la enfermedad al momento del diagnóstico. Diseño. Retrospectivo, longitudinal, descriptivo y observacional. Contexto. Servicio de Inmunología, Instituto Nacional de Pediatría, Ciudad de México. Hospital pediátrico de tercer nivel. Pacientes. Todos los expedientes de pacientes entre 0 y 17 años de edad que fueron diagnosticado con DMJ, que cumplieron con dos o más criterios diagnósticos de Bohan y Peter. Se dividió a la población en dos grupos según tiempo de evolución al momento del diagnóstico: en el grupo 1 (G1) los pacientes con 6 meses o menos y en el grupo 2 (G2), aquellos que tenían más de 6 meses. Material y Métodos. Se investigó sexo, edad, antecedentes de importancia, signos y síntomas, enzimas musculares, estudios inmunológicos, serología para hepatitis A, B, y C y Toxoplasma gondii, electromiografía (EMG), biopsia muscular, serie esofagogástrica (SEG), radiografía de tórax, pruebas de función respiratoria (PFR), electrocardiograma (ECG), electroencefalograma (EEG), valoración oftálmica y renal. Resultados. Se encontraron 102 pacientes, 57 en el G1 y 45 en el G2, la edad promedio fue de 9 años 2 meses con desviación estándar (DE) de 3 años 7 meses. Predominó el sexo femenino en relación 2.3:1. La evoluación del padecimiento tuvo un promedio de 9 meses 10 días con DE de 10 meses 15 días. Los síntomas y signos más frecuentes en ambos grupos fueron el exantema en heliotropo y la debilidad muscular. En el G2 fueron más fecuentes la artritis (p=0.04), hipertricosis (p=0.05) y calcinosis (p=0.03). La ALT (alanin transferasa) fue mayor (p=0.05) y la PCR (proteína C reactiva) positiva con mayor frecuencia (p=0.03) en el G1. Los anticuerpos aCL (anticardiolipina) fueron positivos en cuatro pacientes del G1. Los anticuerpos antitoxoplasma fueron positivos en cuatro pacientes del G1 y uno del G2. No se observaron diferencias significativas entre los grupos al comparar los resultados de EMG, biopsia muscular, SEG, Rx de tórax, PFR, ECG, EEG y valoraciones oftálmica y renal. Discusión. El hecho de que no se detectaran diferencias significativas entre los grupos en la mayor parte de los parámetros estudiados, sugiere que el tiempo de evolución no afecta la expresión clínica de la enfermedad. La artritis, calcinosis e hipertricosis se relacionan con cronicidad. La PCR es un marcador de inflamación del G1 y puede estar en relación al grado de inflamación muscular. Es posible que los anticuerpos aCL y antitoxoplasma fueran positivos con mayor frecuencia en el G1, en relación con el grado de vasculitis; sin embargo, se necesitará evaluar prospectivamente un mayor número de casos para hacer conclusiones válidas