Stem-cell transplantation for children with primary immune deficiencies: A retrospective study of 19 patients from one centre in Mexico.

INTRODUCTION: For many patients with primary immune deficiency (PID), stem-cell transplantation (SCT) may be life-saving. OBJECTIVE: To review our experience of 11 years transplanting children with PID in Mexico. METHODS: Chart review of patients who underwent SCT from 2008 to 2018, to describe their diagnoses, time to transplant, conditioning regime, survival rate and outcomes. All patients received post-transplant cyclophosphamide as graft-versus-host-disease (GVHD) prophylaxis. RESULTS: 19 patients with combined, phagocytic or syndromic PID from 5 states. Twelve of them were male (58%) and 14 survive (79%). Mean age at HSCT was 41.9 months; mean time from diagnosis was 31.2 months. Seven grafts were umbilical cord and 12 haploidentical. The conditioning regime was myeloablative, with five primary graft failures. Two patients had partial and 10 full chimerism. Five patients died within 2 months after transplant. Immune reconstitution was complete in 11 of 19 patients. We found a prevalence of 21% GVHD. DISCUSSION: We describe 19 patients from Mexico with 8 PID diagnoses who underwent allogenic HSCT over a period of 11 years. Survival rate and other outcomes compare well with industrialized countries. We recommend the use of post-transplant cyclophosphamide to prevent GVHD in scenarios of resource scarcity and a lack of HLA-identical donors.

Case Report: DOCK8 Deficiency Without Hyper-IgE in a Child With a Large Deletion.

Autosomal recessive (AR) DOCK8 deficiency is a well-known actinopathy, a combined primary immune deficiency with impaired actin polymerization that results in altered cell mobility and immune synapse. DOCK8-deficient patients present early in life with eczema, viral cutaneous infections, chronic mucocutaneous candidiasis, bacterial pneumonia, and abscesses, together with eosinophilia, thrombocytosis, lymphopenia, and variable dysgammaglobulinemia that usually includes Hyper-IgE. In fact, before its genetic etiology was known, patients were described as having a form of Hyper-IgE syndrome, a name now deprecated in favor of genetic defects. We describe a school-age male patient with a clinical picture suggestive of DOCK8 deficiency, except for high serum IgE or a family history: early onset, failure to thrive, eczema, warts, condyloma, bronchiolitis, pneumonia, recurrent otitis media, bronchiectasis, candidiasis, leukocytosis, eosinophilia, high IgA, low IgG, and low CD4+ T cells. We were able to confirm the diagnosis through protein expression and whole-exome sequencing. We review the clinical, laboratory, and genetic features of 200 DOCK8-deficient patients; at least 4 other patients have had no elevated IgE, and about 40% do not have Hyper-IgE (above 1,000 IU/mL). Despite this, the constellation of signs, symptoms, and findings allow the suspicion of DOCK8 deficiency and other actinopathies.

COVID-19 in the Context of Inborn Errors of Immunity: a Case Series of 31 Patients from Mexico.

INTRODUCTION: Patients with inborn errors of immunity (IEI) have a compromised or inappropriate immune response. Although they might be considered a high-risk group for severe SARS-CoV-2 infection, the reported impact of COVID-19 in these patients has been reassuring, while the differential susceptibility of distinct types of IEI remains unclear. OBJECTIVE: We aimed to describe the findings and outcomes of our known patients with IEI who were diagnosed with COVID-19. METHODS: In a retrospective study from March 2020 to February 2021, four centers in Mexico collected clinical, laboratory, and genetic data from pediatric and adult patients with known diagnoses of IEI who presented with COVID-19, based on compatible symptoms and positive SARS-CoV-2 testing or known household exposure. RESULTS: We report 31 patients with known IEI from Mexico who presented with SARS-CoV-2 infection. Seventy-four percent were male, 52% were pediatric, and 81% survived. Their ages ranged from 5 months to 56 years, with a median of 17 years. Sixty-five percent had predominant antibody deficiencies, 48% were hospitalized, and 26% required ICU. Pediatric patients had a higher hospital admission rate than adults. Inpatient mortality was 40%, and ICU mortality rate was 63%. Forty-eight percent developed pneumonia, while 36% had evidence of hyperinflammation (4 adults and 7 children). Predominant laboratory features were lymphopenia and thrombocytopenia, seen in 70 and 44% of patients, respectively. The serum D-dimer median value was 2.6 (0.5-20.6) µg/mL, and the median highest ferritin value was 1015 (32-10,303) ng/mL. Intravenous immunoglobulin was used in 80% of patients. Other treatments included macrolides (39%) and corticosteroids (29%). Six patients died from secondary infection or uncontrolled systemic inflammation. DISCUSSION: Although impaired immunity due to IEI may be a predisposing factor for severe COVID-19, most of our patients with IEI who acquired the SARS-CoV-2 infection developed a well-tolerated infection and survived, as have more than 80% of worldwide reported patients to date. An impaired immune or inflammatory response may be a predisposing factor for some and a protective factor for others. A systematic review of the literature could help identify those patients at risk of severe disease and complications. Healthcare-associated infections should be aggressively prevented.

Failing to Make Ends Meet: The Broad Clinical Spectrum of DNA Ligase IV Deficiency. Case Series and Review of the Literature.

DNA repair defects are inborn errors of immunity that result in increased apoptosis and oncogenesis. DNA Ligase 4-deficient patients suffer from a wide range of clinical manifestations since early in life, including: microcephaly, dysmorphic facial features, growth failure, developmental delay, mental retardation; hip dysplasia, and other skeletal malformations; as well as a severe combined immunodeficiency, radiosensitivity, and progressive bone marrow failure; or, they may present later in life with hematological neoplasias that respond catastrophically to chemo- and radiotherapy; or, they could be asymptomatic. We describe the clinical, laboratory, and genetic features of five Mexican patients with LIG4 deficiency, together with a review of 36 other patients available in PubMed Medline. Four out of five of our patients are dead from lymphoma or bone marrow failure, with severe infection and massive bleeding; the fifth patient is asymptomatic despite a persistent CD4+ lymphopenia. Most patients reported in the literature are microcephalic females with growth failure, sinopulmonary infections, hypogammaglobulinemia, very low B-cells, and radiosensitivity; while bone marrow failure and malignancy may develop at a later age. Dysmorphic facial features, congenital hip dysplasia, chronic liver disease, gradual pancytopenia, lymphoma or leukemia, thrombocytopenia, and gastrointestinal bleeding have been reported as well. Most mutations are compound heterozygous, and all of them are hypomorphic, with two common truncating mutations accounting for the majority of patients. Stem-cell transplantation after reduced intensity conditioning regimes may be curative.

Type and location of bronchiectasis in a cohort of adults with common variable immunodeficiency / Tipo y localización de bronquiectasias en una cohorte de adultos con inmunodeficiencia común variable

Background: Bronchiectasis are permanent dilatations of the bronchi. Its prevalence in patients with variable common immunodeficiency (CVID) is high, however there is little information regarding the type and location of the same; therefore the objective of this study is to know the type and location of bronchiectasis in a cohort of adult patients with CVID. Methods: It has been made a transversal, observational and descriptive study that included 32 adult patients with diagnosis of CVID according to the criteria of the European Society of Immunodeficiencies (ESID). All patients underwent high resolution pulmonary computed tomography (HRCT), which were interpreted by an expert radiologist. The frequency, type and location of bronchiectasis were reported using descriptive statistics. Results: Thirty-two adult patients, ten men (31.25%) and 22 women (68.7%), were included. 40.6% had bronchiectasis. 23% had a lobe involvement, 15.3% two lobes, 46.1% 3 lobes and 15.3% complete involvement of the parenchyma. The types of bronchiectasis were distributed as follows: tubular 38.4%, varicose 23% and cystic and tubular combinations 15.3%, cystic and varicose 15.3% and cystic, tubular and varicose 7.6%. Conclusions: Our results show that 40% of adult patients with CVID have BQs, usually affecting three pulmonary lobes, located mainly in the right and middle lower lobe; The tubular type, is the most common. Their timely diagnosis and treatment can improve survival and reduce costs for patients and health care.

Introducción: Las bronquiectasias (BQs) son dilataciones permanentes de los bronquios. Su prevalencia en pacientes con inmunodeficiencia común variable (IDCV) es alta, sin embargo existe escasa información respecto al tipo y localización de las mismas. El objetivo de este estudio es conocer el tipo y localización de las bronquiectasias en una cohorte de pacientes adultos portadores de IDCV. Métodos: Estudio transversal, observacional y descriptivo que incluyó a 32 pacientes adultos con diagnóstico de IDCV de acuerdo con los criterios de la Sociedad Europea de Inmunodeficiencias. A todos se les realizó tomografía de alta resolución pulmonar, las cuales fueron interpretadas por un médico radiólogo experto. Se reportó la frecuencia, tipo y localización de las bronquiectasias mediante estadística descriptiva.Resultados: se incluyeron 32 pacientes adultos, diez hombres y 22 mujeres. El 40.6% presentaron bronquiectasias. El 23% tenía afección en un lóbulo, el 15.3% dos lóbulos, 46.1% 3 lóbulos y el 15.3% afectación completa del parénquima; distribuidos de la siguiente manera: tubulares 38.4%, varicosas 23% y las combinaciones quísticas y tubulares 15.3%, quísticas y varicosas 15.3% y quísticas, tubulares y varicosas 7.6%. Conclusión: Nuestros resultados muestran que el 40% de los pacientes adultos con IDCV tienen BQs, suelen afectar tres lóbulos pulmonares, el tipo más común fue el tubular. Su diagnóstico y tratamiento oportuno puede mejorar la supervivencia y reducir los costos para el paciente y las instituciones de salud.