Publications by authors named "Matias Oleastro"

Background: Severe combined immunodeficiency secondary to adenosine deaminase deficiency is rare. The deficiency of this enzyme results in the accumulation of substrates in the tissues, including the brain. Clinical signs of neurological involvement may include seizures, neurodevelopmental disorders, hypotonia, and sensorineural hearing loss.

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Background: Inborn Errors of Immunity (IEI) comprise several genetic anomalies that affect different components of the innate and adaptive responses, predisposing to infectious diseases, autoimmunity and malignancy. Different studies, mostly in adults, have reported a higher prevalence of cancer in IEI patients. However, in part due to the rarity of most of these IEI subtypes (classified in ten categories by the Primary Immunodeficiency Committee of the International Union of Immunological Societies), it is difficult to assess the risk in a large number of patients, especially during childhood.

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Article Synopsis
  • The CDC and ACIP endorse COVID-19 vaccination for patients with inborn errors of immunity (IEI), but there's limited knowledge on its safety and impact on infection severity in these patients.
  • A study involving a registry of 1,245 IEI patients across 24 countries was conducted to gather data on vaccination frequency, safety, and effectiveness, revealing that 64.7% were vaccinated, primarily with mRNA vaccines.
  • Results showed that vaccinated patients had significantly lower hospitalization and ICU admission rates when infected with COVID-19, indicating that vaccination is both safe and effective in reducing the severity of the disease in IEI patients.
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CARD11-associated diseases are monogenic inborn errors of immunity involving immunodeficiency, predisposition to malignancy and immune dysregulation such as lymphoproliferation, inflammation, atopic and autoimmune manifestations. Defects in  can present as mutations that confer a complete or a partial loss of function (LOF) or contrarily, a gain of function (GOF) of the affected gene product. We report clinical characteristics, immunophenotypes and genotypes of 15 patients from our center presenting with CARD11-associated diseases.

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Microsporum gypseum is a geophilic fungus that can cause inflammatory skin lesions in heathy people. More extensive lesions have been described in immunocompromised patients. We present a patient with extensive dermatophytosis, which mycological examination led the identification of Candida sp, Epidermophyton Floccosum and Trichophyton tonsurans and showed poor response to treatment with griseofulvina and itraconazol at usual doses.

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  • Autosomal recessive complete IRF8 deficiency is a rare immune disorder leading to severe infections and absence of specific blood cells, with only three other cases previously documented.
  • An Argentinian child with severe pulmonary issues and multiple infections was studied, revealing two genetic mutations in the IRF8 gene responsible for the condition.
  • The findings suggest that this genetic mutation hampers immune cell development, linking AR complete IRF8 deficiency to pulmonary alveolar proteinosis, and highlighting the need for awareness of this disorder in similar pediatric cases.
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  • Inherited bone marrow failure syndromes (IBMFSs) are disorders that lead to the inadequate production of blood cells, with dyskeratosis congenita (DC) and its severe form, Høyeraal-Hreidarsson (HH) syndrome, being prominent examples associated with short telomeres.
  • Recent research identified changes in the Apollo gene in three unrelated patients with DC/HH symptoms, which included bone marrow failure, immune cell deficiencies, and developmental issues, all linked to specific genetic variants affecting a critical amino acid in the Apollo protein.
  • The study revealed that Apollo-deficient cells displayed chromosome instability and DNA repair defects, indicating that these genetic mutations contribute to a severe IBMFS while maintaining normal telomere length
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Purpose: X-linked inhibitor of apoptosis protein (XIAP) deficiency, also known as the X-linked lymphoproliferative syndrome of type 2 (XLP-2), is a rare immunodeficiency characterized by recurrent hemophagocytic lymphohistiocytosis, splenomegaly, and inflammatory bowel disease. Variants in XIAP including missense, non-sense, frameshift, and deletions of coding exons have been reported to cause XIAP deficiency. We studied three young boys with immunodeficiency displaying XLP-2-like clinical features.

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Article Synopsis
  • * A family is reported with a heterozygous mutation in NFKB2 that results in no protein expression and reduced mRNA, leading to decreased NFKB2 activity (haploinsufficiency) and associated clinical immunodeficiency.
  • * Key immunological features include abnormal B cell development, low antibody levels, and specific signaling issues, which further clarify the genetics behind NFKB2-related immunodeficiency disorders.
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Purpose: Caspase-associated recruitment domain-9 (CARD9) deficiency is an inborn error of immunity that typically predisposes otherwise healthy patients to single fungal infections and the occurrence of multiple invasive fungal infections is rare. It has been described as the first known condition that predisposes to extrapulmonary Aspergillus infection with preserved lungs. We present a patient that expands the clinical variability of CARD9 deficiency.

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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.

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  • - The study investigates isolated congenital asplenia (ICA), a rare condition affecting the lymphoid organ, linked to mutations in the ribosomal protein SA gene, with a significant number of cases showing a connection to protein-coding mutations and some affecting mRNA splicing.
  • - New research identified 11 additional mutations in the ribosomal protein SA gene and revealed that a majority of the studied kindreds (41%) and over half of patients (55%) have mutations that can lead to ICA.
  • - Notably, the study highlights the variable expressiveness of these mutations, with some demonstrating incomplete penetrance, suggesting that not all individuals with mutations will develop symptoms of ICA.
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Biallelic loss-of-function (LOF) mutations of the NCF4 gene, encoding the p40phox subunit of the phagocyte NADPH oxidase, have been described in only 1 patient. We report on 24 p40phox-deficient patients from 12 additional families in 8 countries. These patients display 8 different in-frame or out-of-frame mutations of NCF4 that are homozygous in 11 of the families and compound heterozygous in another.

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WHIM syndrome is a primary autosomal dominant immuno deficiency due to CXCR4 mutations characterized by mucocutaneous warts, hypogammaglobulinemia, recurrent bacterial infections and myelokathesis. Treatment consists in prophylactic antibiotics, immunoglobulin replacement and granulocyte or granulocyte/monocyte colony stimulating factors. We present the case of a 21 year old woman who showed leukopenia at 10 months of age and one year later multiple infections with hypogammaglobulinemia requiring intravenous immunoglobulin.

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Few monogenic causes for severe manifestations of common allergic diseases have been identified. Through next-generation sequencing on a cohort of patients with severe atopic dermatitis with and without comorbid infections, we found eight individuals, from four families, with novel heterozygous mutations in CARD11, which encodes a scaffolding protein involved in lymphocyte receptor signaling. Disease improved over time in most patients.

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Background: Germline heterozygous mutations in human signal transducer and activator of transcription 1 (STAT1) can cause loss of function (LOF), as in patients with Mendelian susceptibility to mycobacterial diseases, or gain of function (GOF), as in patients with chronic mucocutaneous candidiasis. LOF and GOF mutations are equally rare and can affect the same domains of STAT1, especially the coiled-coil domain (CCD) and DNA-binding domain (DBD). Moreover, 6% of patients with chronic mucocutaneous candidiasis with a GOF STAT1 mutation have mycobacterial disease, obscuring the functional significance of the identified STAT1 mutations.

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Chronic mucocutaneous candidiasis (CMC) is defined as recurrent or persistent infection of the skin, nails, and/or mucosae with commensal Candida species. The first genetic etiology of isolated CMC-autosomal recessive (AR) IL-17 receptor A (IL-17RA) deficiency-was reported in 2011, in a single patient. We report here 21 patients with complete AR IL-17RA deficiency, including this first patient.

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Background: Common variable immunodeficiency (CVID) is a heterogeneous syndrome characterized by impaired immunoglobulin production and usually presents with a normal quantity of peripheral B cells. Most attempts aiming to classify these patients have mainly been focused on T- or B-cell phenotypes and their ability to produce protective antibodies, but it is still a major challenge to find a suitable classification that includes the clinical and immunologic heterogeneity of these patients.

Objective: In this study we evaluated the late stages of B-cell differentiation in a heterogeneous population of patients with pediatric-onset CVID to clinically correlate and assess their ability to perform somatic hypermutation (SHM), class-switch recombination (CSR), or both.

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X-linked agammaglobulinemia (XLA) is characterized by absent or severely reduced B cells, low or undetectable immunoglobulin levels and clinically by extracellular bacterial infections which mainly compromise the respiratory tract as well as recurrent diarrheas. The mainstay of treatment is gammaglobulin replacement therapy, which allows most patients to reach adulthood with high quality of life. We analyzed the clinical features of 14 patients over 18 years of age with XLA diagnosis that received treatment in our unit from the year 2003, the date the first patient was derived, until 2015.

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