Cecilia Poli

• M.D. Ph.D.
• Managing Director at Universidad del Desarrollo

This report provides an updated classification of inborn errors of immunity (IEIs) involving 508 different genes and 17 phenocopies. Of these, we report 67 novel monogenic defects and 2 phenocopies due to neutralizing anti-cytokine autoantibodies or somatic mutations, which either have been discovered since the previous update (published June 2022)...

Here, we report the 2024 update of the phenotypic classification by the International Union of Immunological Societies (IUIS) expert committee (EC) on inborn errors of immunity (IEI), which accompanies and complements the 2024 genotypic classification. The aim of this classification is to help diagnosis for clinicians at the bedside and focuses on...

Human recombination-activating gene (RAG) deficiency can manifest with distinct clinical and immunological phenotypes. By applying a multiomics approach to a large group of RAG -mutated patients, we aimed at characterizing the immunopathology associated with each phenotype. Although defective T and B cell development is common to all phenotypes, pa...

Background Copy number variation (CNV) is a class of genomic Structural Variation (SV) that underlie genomic disorders and can have profound implications for health. Short-read genome sequencing (sr-GS) enables CNV calling for genomic intervals of variable size and across multiple phenotypes. However, unresolved challenges include an overwhelming n...

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)...

Background and aim Post-COVID-19 condition (PCC) encompasses long-lasting symptoms in individuals with COVID-19 and is estimated to affect between 31–67% of patients, with women being more commonly affected. No definitive biomarkers have emerged in the acute stage that can help predict the onset of PCC, therefore we aimed at describing sex-disaggre...

The history of autoinflammatory diseases goes back centuries, with early observations and descriptions found in ancient medical texts and historical records. Although detailed descriptions of familial periodic fever syndromes only appeared in the second half of the 20th century , periodic fevers have been documented since antiquity. Since the first...

Mutations in the N-terminal WD40 domain of coatomer protein complex subunit α (COPA) cause a type I interferonopathy, typically characterized by alveolar hemorrhage, arthritis and nephritis. We described three heterozygous mutations in the C-terminal domain (CTD) of COPA (p.C1013S, p.R1058C and p.R1142X) in six children from three unrelated familie...

Rare diseases affect millions of people worldwide, and most have a genetic etiology. The incorporation of next-generation sequencing into clinical settings, particularly exome and genome sequencing, has resulted in an unprecedented improvement in diagnosis and discovery in the past decade. Nevertheless, these tools are unavailable in many countries...

Inborn errors of immunity (IEI) or primary immune deficiencies (PIDD) are caused by variants in genes encoding for molecules that are relevant to the innate or adaptive immune response. To date, defects in more than 450 different genes have been identified as causes of IEI, causing a constellation of heterogeneous clinical manifestations ranging fr...

The study of primary immunodeficiencies or inborn errors of immunity continues to drive our knowledge of the function of the human immune system. From the outset, the study of inborn errors has focused on unraveling genetic etiologies and molecular mechanisms. Aided by the continuous growth in genetic diagnostics, the field has moved from the study...

Los síndromes autoinflamatorios sistémicos se caracterizan por inflamación sistémica o de órganos, recurrente sin causa infecciosa o neoplásica evidente. Su presentación clínica es heterogénea y puede caracterizarse por episodios de fiebre recurrente, inflamación sistémica severa con activación macrofágica, inflamación ósea o cutánea persistente. E...

Patients with autoimmune polyendocrinopathy syndrome type 1 (APS-1) caused by autosomal recessive AIRE deficiency produce autoantibodies that neutralize type I interferons (IFNs) 1,2 , conferring a predisposition to life-threatening COVID-19 pneumonia ³ . Here we report that patients with autosomal recessive NIK or RELB deficiency, or a specific ty...

Rare diseases affect millions of people worldwide, and most have a genetic etiology. The incorporation of next-generation sequencing into clinical settings, particularly exome and genome sequencing, has resulted in an unprecedented improvement in diagnosis and discovery in the past decade. Nevertheless, these tools are unavailable in many countries...

Background and objectives: Interferons have been identified as a potential treatment alternative for coronavirus disease 2019. This study assessed the safety, tolerability, bioavailability, and biological activity of inhaled interferon-α2b (IFN)-α2b in healthy adults. Methods: A double-blind, randomized, phase I clinical trial was conducted with...

Chronic kidney disease (CKD) patients have an increased risk of morbidity and mortality following SARS-CoV-2 infection. Vaccination in these patients is prioritized, and monitoring of the immune response is paramount to define further vaccination strategies. This prospective study included a cohort of 100 adult CKD patients: 48 with kidney transpla...

Patients with inborn errors of the alternative NF-κB pathway have low thymic AIRE expression, leading to the development of auto-Abs neutralizing type I IFNs, and severe viral diseases.

Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of OAS1 , OAS2 , or RNASEL in five unrelated children with MIS-C. The cytosolic dsRNA-sensing OAS1 and OAS2 generate 2′-5′-linked oligoadenylates (2-5A) that activate the ssRNA-degrading RNase...

Multisystem Inflammatory Syndrome in Children (MIS-C) is a systemic inflammatory condition that follows SARS-CoV2 infection or exposure in children. Clinical presentations are highly variable and include fever, gastrointestinal (GI) disease, shock, and Kawasaki Disease-like illness (MIS-C/KD). Compared to patients with acute COVID, patients with MI...

Human NK cell deficiency (NKD) is a primary immunodeficiency in which the main clinically relevant immunological defect involves missing or dysfunctional NK cells. Here, we describe a familial NKD case in which 2 siblings had a substantive NKD and neutropenia in the absence of other immune system abnormalities. Exome sequencing identified compound...

Aim: Interferons (IFNs) have been identified as a potential treatment alternative for Coronavirus Disease 19 (COVID-19). This study assessed the safety, tolerability, bioavailability, and biological activity of inhaled interferon-α2b (IFN-α2b) in healthy adults. Methods: A double-blind, randomized, phase 1 clinical trial was conducted with two coho...

Aim: Interferons (IFNs) have been identified as a potential treatment alternative for Coronavirus Disease 19 (COVID-19). This study assessed the safety, tolerability, bioavailability, and biological activity of inhaled interferon-α2b (IFN-α2b) in healthy adults. Methods: A double-blind, randomized, phase 1 clinical trial was conducted with two coho...

Multisystem Inflammatory Syndrome in Children (MIS-C) is a systemic inflammatory condition that follows SARS-CoV2 infection or exposure in children. Clinical presentations are highly variable and include fever, gastrointestinal (GI) disease, shock, and Kawasaki Disease-like illness (MIS-C/KD). Compared to patients with acute COVID, patients with MI...

Background Multisystemic inflammatory syndrome in children (MIS-C) is a life-threatening disease that occurs 2-5 weeks after SARS-CoV-2 exposure and is characterized by severe multisystemic inflammation. Early recognition of MIS-C is key to prognosis, therefore establishing clinical and laboratory biomarkers that predict complications is urgently n...

Pediatric Coronavirus Disease 2019 (pCOVID-19) is rarely severe; however, a minority of children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might develop multisystem inflammatory syndrome in children (MIS-C), with substantial morbidity. In this longitudinal multi-institutional study, we applied multi-omics (analysis...

Objective Autoinflammatory type I interferonopathies, chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature/proteasome‐associated autoinflammatory syndrome (CANDLE/PRAAS), stimulator of interferon genes (STING)–associated vasculopathy with onset in infancy (SAVI), and Aicardi‐Goutières syndrome (AGS) are rare and clin...

The antibody profile against autoantigens previously associated with autoimmune diseases and other human proteins in patients with COVID-19 or multisystem inflammatory syndrome in children (MIS-C) remains poorly defined. Here we show that 30% of adults with COVID-19 had autoantibodies against the lung antigen KCNRG, and 34% had antibodies to the SL...

Proteasome dysfunction can lead to autoinflammatory disease associated with elevated type I interferon (IFN-αβ) and NF-κB signaling; however, the innate immune pathway driving this is currently unknown. Here, we identified protein kinase R (PKR) as an innate immune sensor for proteotoxic stress. PKR activation was observed in cellular models of dec...

Purpose Mendelian disease genomic research has undergone a massive transformation over the past decade. With increasing availability of exome and genome sequencing, the role of Mendelian research has expanded beyond data collection, sequencing, and analysis to worldwide data sharing and collaboration. Methods Over the past 10 years, the National I...

Objective Autoinflammatory type I interferonopathies, chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature/proteasome-associated autoinflammatory syndrome (CANDLE/PRAAS), stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI) and Aicardi-Goutières syndrome (AGS) are rare and clini...

The autoantibody profile associated with known autoimmune diseases in patients with COVID-19 or multisystem inflammatory syndrome in children (MIS-C) remains poorly defined. Here we show that adults with COVID-19 had a moderate prevalence of autoantibodies against the lung antigen KCNRG, and SLE-associated Smith autoantigen. Children with COVID-19...

Pediatric COVID-19 (pCOVID-19) is rarely severe, however a minority of SARS-CoV-2-infected children may develop MIS-C, a multisystem inflammatory syndrome with significant morbidity. In this longitudinal multi-institutional study, we used multi-omics to identify novel time- and treatment-related immunopathological signatures in children with COVID-...

Background Filaggrin (FLG) loss-of-function variants are major genetic risk factors for atopic dermatitis (AD), but these have not been studied in Latin American populations with and without AD. Methods FLG variants R501X and 2282del4 were genotyped in 275 Chilean adults with and without AD from the “Early origins of allergy and asthma” (ARIES) co...

Background Pediatric non-malignant lymphoproliferative disorders (PLPD) are clinically and genetically heterogeneous. Long-standing immune dysregulation and lymphoproliferation in children may be life-threatening, and a paucity of data exists to guide evaluation and treatment of children with PLPD. Objective The primary objective of this study was...

Introducción: El síndrome inflamatorio multisistémico pediátrico asociado a SARS-CoV-2 (MIS-C) se caracteriza por un estado hiperinflamatorio producto de una tormenta de citoquinas, evidenciado en alteracio nes del laboratorio hematológico y proteínas de fase aguda. Objetivo: Describir las características clínicas y de laboratorio de pacientes hos...

Multisystem inflammatory syndrome temporally associated with COVID-19 (MIS-C) is a post-infectious complication described in children and adolescents with previous exposure to SARS-CoV-2. Because of its potential to evolve to severe disease -including cardiovascular impairment and multiple organ failure it requires a prompt diagnosis and appropriat...

Inborn errors of immunity that present with concomitant immunodeficiency and auto-inflammation are therapeutically challenging; furthermore, complexity is added when they are caused by mutations in genes that encode for proteins expressed beyond immune cells. The ubiquitin-proteasome system is the main intracellular proteolytic machinery and partic...

Lysinuric protein intolerance (LPI) is an inborn error of metabolism caused by defective transport of cationic amino acids in epithelial cells of intestines, kidneys and other tissues as well as non-epithelial cells including macrophages. LPI is caused by biallelic, pathogenic variants in SLC7A7 . The clinical phenotype of LPI includes failure to t...

Inborn errors of immunity are genetic defects of the immune system, causing increased susceptibility to infection, autoinflammation, autoimmunity and immune dysregulation. Next-generation sequencing has enabled exponential identification of novel inborn errors of immunity due to mutations in genes encoding for proteins that participate in the immun...

Bi‐allelic TECPR2 variants have been associated with a complex syndrome with features of both a neurodevelopmental and neurodegenerative disorder. Here, we provide a comprehensive clinical description and variant interpretation framework for this genetic locus. Through an international collaboration, we identified 17 individuals from 15 families wi...

This is a Brighton Collaboration Case Definition of the term “Multisystem Inflammatory Syndrome in Children and Adults (MIS-C/A)” to be utilized in the evaluation of adverse events following immunization. The case definition was developed by topic experts convened by the Coalition for Epidemic Preparedness Innovations (CEPI) in the context of activ...

Introducción: La infección por virus SARS-CoV-2 responsable de la pandemia actual, es una entidad clínica y fisiopatológica nueva y en desarrollo, cuyo control aún es incierto mientras no contemos con una vacuna efectiva y de distribución universal. Descrita inicialmente como una enfermedad respiratoria mayoritariamente de adultos, los niños tambié...

La inmunodeficiencia combinada severa (IDCS) corresponde a una de las formas más graves de inmunodeficiencia primaria, existiendo escasos datos nacionales sobre ésta.Objetivo: describir la epidemiología, complicaciones, pronóstico y uso de la vacuna BCG en pacientes chilenos con IDCS.Pacientes y Método: Estudio retrospectivo de pacientes diagnostic...

La inmunodeficiencia combinada severa (IDCS) corresponde a una de las formas más graves de inmunodeficiencia primaria, existiendo escasos datos nacionales sobre ésta.Objetivo: describir la epidemiología, complicaciones, pronóstico y uso de la vacuna BCG en pacientes chilenos con IDCS.Pacientes y Método: Estudio retrospectivo de pacientes diagnostic...

We describe a case of Pediatric Inflammatory Multisystem Syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in an 8-year-old child. The patient developed multiorgan dysfunction, including mixed shock, cardiac dysfunction with myocarditis, pneumonia, acute kidney failure, and gastrointestinal involvement characterized by inflammation of the wa...

Introducción: La inmunodeficiencia combinada severa (IDCS) corresponde a una de las formas más graves de inmunodeficiencia primaria, existiendo escasos datos nacionales sobre ésta. Objetivo: describir la epidemiología, complicaciones, pronóstico y uso de la vacuna BCG en pacientes chilenos con IDCS. Pacientes y Método: Estudio retrospectivo de pa...

Introducción: El Síndrome Inflamatorio Pediátrico Multisistémico (PIMS) ha emergido como una nueva enfermedad en niños, secundaria a infección por SARSCoV-2. Se caracteriza por presentar compromiso multiorgánico con parámetros inflamatorios elevados y manifestaciones clínicas graves, siendo el corazón el órgano más severamente comprometido. Objeti...

Introduction/objectives: An interleukin-6 inhibition strategy could be effective in selected COVID-19 patients. The objective is to present our experience of tocilizumab use in patients with severe COVID-19. Methods: Observational retrospective cohort study. Hospitalized patients were evaluated by our multidisciplinary team for eventual use of toci...

Abstract Background There is uncertainty about the impact of SARS-CoV-2 infection in individuals with rare inborn errors of immunity (IEI), a population at risk of developing severe COVID-19. This is relevant not only for these patients but also the general population, as studies of IEIs can unveil key requirements for host defense. Objective De...

Agammaglobulinemia is the most profound primary antibody deficiency that can occur due to an early termination of B-cell development. We here investigated three novel patients, including the first known adult, from unrelated families with agammaglobulinemia, recurrent infections, and hypertrophic cardiomyopathy (HCM). Two of them also presented wit...

Introduction/objectives: An interleukin-6 inhibition strategy could be effective in selected COVID-19 patients. The objective is to present our experience of tocilizumab use in patients with severe COVID-19. Methods: Observational retrospective cohort study. Hospitalized patients were evaluated by our multidisciplinary team for eventual use of toci...

An inherited disorder makes WAVEs The WAVE regulatory complex (WRC) is a multiunit complex that regulates actin cytoskeleton formation. Although other actin-regulatory proteins modulate human immune responses, the precise role for the WRC has not yet been established. Cook et al. studied five patients from four unrelated families who harbor missens...

Las inmunodeficiencias primarias (IDP) son un conjunto de cerca de 350 enfermedades genéticas que afectan el funcionamiento del sistema inmunológico. Los avances en diagnóstico genético han permitido describir nuevos defectos en el sistema inmune, ampliando el espectro de manifestaciones de las IDP más allá de la susceptibilidad a infecciones. Aunq...

Primary immunodeficiencies (PIDs) are a set of about 350 genetic disorders that affect the normal function of the immune system. Advances in genetic diagnosis have allowed the description of new defects in the immune system, broadening the clinical spectrum of PIDs' manifestations beyond susceptibility to infection. Although most PIDs present with...

Type I interferonopathies cover a phenotypically heterogeneous group of rare genetic diseases including the recently described proteasome-associated autoinflammatory syndromes (PRAAS). By definition, PRAAS are caused by inherited and/or de novo loss-of-function mutations in genes encoding proteasome subunits such as PSMB8, PSMB9, PSMB7, PSMA3, or p...

Introduction: Pediatric non-malignant lymphoproliferative disorders (LPDs) are a clinically and genetically heterogeneous. While transient lymphadenopathy is extremely common and rarely dangerous, long-standing immune dysregulation and lymphoproliferation in children may be life-threatening. Data to guide evaluation and treatment of children with b...

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...

Nuclear factor kappa-B subunit 2 (NF-κB2/p100/p52), encoded by NFKB2 (MIM: 164012) belongs to the NF-κB family of transcription factors that play a critical role in inflammation, immunity, cell proliferation, differentiation and survival. Heterozygous C-terminal mutations in NFKB2 have been associated with early-onset common variable immunodeficien...

Immunodeficiency often coincides with immune hyperresponsiveness such as autoimmunity, lymphoproliferation, or atopy, but the molecular basis of this paradox is typically unknown. We describe four families with immunodeficiency coupled with atopy, lymphoproliferation, cytokine overproduction, hemophagocytic lymphohistocytosis, and autoimmunity. We...

Objectives This study aimed to review the literature on the repercussions of the different inborn errors of immunity on growth, drawing attention to the diagnosis of this group of diseases in patients with growth disorders, as well as to enable the identification of the different causes of growth disorders in patients with inborn errors of immunity...

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...

Objectives: This study aimed to review the literature on the repercussions of the different inborn errors of immunity on growth, drawing attention to the diagnosis of this group of diseases in patients with growth disorders, as well as to enable the identification of the different causes of growth disorders in patients with inborn errors of immuni...

Purpose of review: Advances in sequencing techniques and systematic cohort-analysis of patients with autoinflammatory phenotypes have enabled a burst in the recognition of new autoinflammatory diseases and contributed to the description of the mechanisms involved in autoinflammation. This review focuses on new genetic and mechanistic discoveries t...

Background: CARD11 encodes a scaffold protein in lymphocytes that links antigen receptor engagement with downstream signaling to NF-κB, JNK, and mTORC1. Germline CARD11 mutations cause several distinct primary immune disorders in humans, including SCID (biallelic null mutations), B cell Expansion with NF-κB and T cell Anergy (BENTA; heterozygous,...

Premature termination codon (PTC)-bearing transcripts are often degraded by nonsense-mediated decay (NMD) resulting in loss-of-function (LoF) alleles. However, not all PTCs result in LoF mutations, i.e., some such transcripts escape NMD and are translated to truncated peptide products that result in disease due to gain-of-function (GoF) effects. Si...

The proteasome processes proteins to facilitate immune recognition and host defense. When inherently defective, it can lead to aberrant immunity resulting in a dysregulated response that can cause autoimmunity and/or autoinflammation. Biallelic or digenic loss-of-function variants in some of the proteasome subunits have been described as causing a...

The HLH-2004 criteria are used to diagnose hemophagocytic lymphohistiocytosis (HLH), yet concern exists for their misapplication, resulting in suboptimal treatment of some patients. We sought to define the genomic spectrum and associated outcomes of a diverse cohort of children who met the HLH-2004 criteria. Genetic testing was performed clinically...

Background: The epidemiology and hospitalisation trends of primary immunodeficiency (PID) in Chile are unknown. We aimed to evaluate hospitalisation trends and demographic characteristics of PID admissions in Chile. Methods: PID admissions between 2001 and 2010 (ICD-10 codes D70.0, D70.4, D71, 72.0, D76.1, D80-D84, E70.3, G11.3) were reviewed us...

To kill target cells, natural killer (NK) cells organize signaling from activating and inhibitory receptors to form a lytic synapse. Wiskott-Aldrich syndrome (WAS) patients have loss-of-function mutations in the actin regulator WASp and suffer from immunodeficiency with increased risk to develop lymphoreticular malignancies. NK cells from WAS patie...

Background: Primary immunodeficiency diseases (PIDDs) are clinically and genetically heterogeneous disorders thus far associated with mutations in more than 300 genes. The clinical phenotypes derived from distinct genotypes can overlap. Genetic etiology can be a prognostic indicator of disease severity and can influence treatment decisions. Objec...

Background/Purpose Pediatric rheumatologic diseases (PRDs) comprise a group of complex conditions that involve considerable disease burden and are sometimes life‐threatening. The American College of Rheumatology and the British Society for Pediatric and Adolescent Rheumatology recommend that a Pediatric Rheumatologist (PR) be involved in the care o...

Childhood parotid swelling has a number of differential diagnosis mostly of inflammatory origin. Pneumoparotitis is an uncommon cause of parotid inflammation. It is caused by an excessive increase of intraoral pressure and secondary passage of air into the Stensen or Stenon duct and its glandular branches. Diagnostic clues can usually be obtained b...

Childhood parotid swelling has a number of differential diagnosis mostly of inflammatory origin. Pneumoparotitis is an uncommon cause of parotid inflammation. It is caused by an excessive increase of intraoral pressure and secondary passage of air into the Stensen or Stenon duct and its glandular branches. Diagnostic clues can usually be obtained b...

Oral contraceptives (OCs) may be used for therapeutic or family planning purposes. Inhibition of ovulation is the main mechanism implicated in both instances, though post-fertilization effects described as secondary mechanism in effective contraception are ethically unacceptable for some patients who identify the start of human person at fertilizat...