RESUMO
Actinrelated protein 2/3 complex subunit 1B (ARPC1B) deficiency is an inborn error of immunity (IEI) characterized by a combination of immunodeficiency and immune dysregulation and classified as an IEI with allergic manifestations. Here, we describe two patients with pathogenic variants in the ARPC1B gene. The first patient presented with eczema and bronchospasm at six months of age. The second patient presented with eczema and milk protein allergy at five months of age. The c.899_944 (p.Glu300Glyfs*7) pathogenic variant was previously described, whereas the c.863del (p.Pro288Leufs*9) variant was novel. ARPC1B deficiency should be considered because of the severe allergic manifestations at an early age.
Assuntos
Eczema , Hipersensibilidade Alimentar , Síndromes de Imunodeficiência , Hipersensibilidade a Leite , Animais , Humanos , Lactente , Complexo 2-3 de Proteínas Relacionadas à Actina/genética , Alérgenos , Eczema/genética , Síndromes de Imunodeficiência/genética , Leite , Hipersensibilidade a Leite/diagnóstico , Hipersensibilidade a Leite/genéticaRESUMO
PURPOSE: We aimed to describe the clinical, immunological, and genetic features of patients with DOCK8 deficiency (DOCK8-Def) in a tertiary care center for children. METHODS: Retrospective chart review of patients' clinical, immunological, and genetic characteristics with DOCK8-Def. Genetic analysis was performed with targeted- or whole-exome sequencing; we also assessed DOCK8 protein expression and a lymphoproliferation assay and analyzed survival by the Kaplan-Meier method. RESULTS: We described 11 patients from 8 unrelated kindreds. The median age at symptoms' onset was 10 months (range 1-54 months). The median follow-up time was 53.4 months (4.8-118.8). All patients presented eczema and recurrent sinopulmonary and cutaneous infections. Besides those symptoms, the most frequent manifestations were bronchiectases (8/11), food allergies (6/11), and severe infections (6/11). Infrequent characteristics were detection of CMV in bronchial lavage, C. parvum-driven sclerosing cholangitis, Takayasu vasculitis, neurological syndromes, pulmonary tuberculosis, and lymphomatoid granulomatosis. CONCLUSION: DOCK8-Def has a broad spectrum of manifestations, including allergy, autoimmunity, inflammation, infection, and cancer. The hallmark of this inborn error of immunity is IEI-associated eczema with eosinophilia and increased IgE. Here, we report six new mutations causing human DOCK8 deficiency and symptoms previously unrecognized to occur in DOCK8-Def. Therefore, an early diagnosis of DOCK8-Def is essential to facilitate an adequate treatment such as HSCT.
Assuntos
Eczema , Hipersensibilidade , Síndrome de Job , Criança , Humanos , Lactente , Pré-Escolar , Estudos Retrospectivos , Síndrome de Job/genética , Eczema/epidemiologia , Eczema/genética , Mutação , Fatores de Troca do Nucleotídeo Guanina/genéticaRESUMO
Raspberries (Rubus spp) are temperate climate fruits with profitable high returns and have the potential for diversification of fruit growing in mid to low-latitude regions. However, there are still no cultivars adapted to climatic conditions and high pressure of diseases that occurs in tropical areas. In this context, our objective was to evaluate the genetic diversity from a 116 raspberry genotypes panel obtained from interspecific crosses in a testcross scheme with four cultivars already introduced in Brazil. The panel was genotyped via genotyping-by-sequencing. 28,373 and 27,281 SNPs were obtained, using the species R. occidentalis and R. idaeus genomes as references, respectively. A third marker dataset was constructed consisting of 41,292 non-coincident markers. Overall, there were no differences in the results when using the different marker sets for the subsequent analyses. The mean heterozygosity was 0.54. The average effective population size was 174, indicating great genetic variability. The other analyses revealed that the half-sibling families were structured in three groups. It is concluded that the studied panel has great potential for breeding and further genetic studies. Moreover, only one of the three marker matrices is sufficient for diversity studies.
Assuntos
Basidiomycota , Doenças do Tecido Conjuntivo , Eczema , Doenças do Sistema Imunitário , Rubus , Dermatopatias Bacterianas , Humanos , Melhoramento Vegetal , Brasil , Doenças das Plantas/genéticaRESUMO
BACKGROUND: Wiskott-Aldrich syndrome is an Inborn Error of Immunity characterized by thrombocytopenia, small platelets, severe eczema, recurrent infections, tendency to autoimmune diseases and neoplasms. The diagnosis of the syndrome can be difficult, especially when platelets are of normal size. CASE REPORT: A three-year-old male patient was referred to a specialized sector of university hospital for presenting acute otitis media that progressed to sepsis by Haemophilus influenzae. At one month of age, he had been diagnosed with autoimmune thrombocytopenia, and splenectomy was performed at two years of age. During follow-up, three hospitalizations were necessary: an infection by Streptococcus pneumoniae, which progressed to sepsis; one due to exacerbation of eczema, isolating S. epidermidis; another due to fever of undetermined origin. The tests showed normal number of platelets after splenectomy, platelets always with normal size. At age four, tests were performed: IgE 3128 Ku/L; IgA, IgG, and normal anti-polysaccharide antibodies; decreased IgM; decrease CD19, TCD4, naïve T and B; increased TCD8; normal NK. A diagnostic hypothesis of "probable" WAS was made. Genetic research has identified the c.295C>T mutation in the WAS gene. CONCLUSIONS: The case reported expressed a new mutation in the SWA gene, characterized by clinical manifestations of the mild phenotype of Wiskott-Aldrich syndrome, with thrombocytopenia, platelets of normal size, and X-linked inheritance. It is important to establish the early diagnosis and treatment to offer a better quality of life in these patients.
ANTECEDENTES: El síndrome de Wiskott-Aldrich es un error innato de la inmunidad, distinguido por trombocitopenia, plaquetas pequeñas, eccema severo, infecciones recurrentes, y susceptibilidad a enfermedades autoinmunes y neoplasias. El diagnóstico es difícil de establecer, especialmente cuando las plaquetas son de tamaño normal. REPORTE DE CASO: Paciente masculino de 3 años, enviado al Hospital Universitario da Santa Casa de São Paulo, Brasil, por otitis media aguda, con evolución a sepsis por Haemophilus influenzae. Al mes de edad fue diagnosticado con trombocitopenia autoinmune, y a los 2 años se llevó a cabo explenectomía. Durante el seguimiento requirió tres hospitalizaciones: una por infección por Streptococcus pneumoniae, que evolucionó a sepsis; otra por exacerbación de eccema, aislándose S. epidermidis, y la última por fiebre de origen indeterminado. Las pruebas de laboratorio informaron: concentración de plaquetas dentro de los valores de referencia después de la esplenectomía, y de tamaño normal. A los 4 años se efectuaron nuevas pruebas, que reportaron: IgE 3128 kU/L; IgA, IgG y anticuerpos anti-polisacáridos normales; disminución de IgM y de CD19, TCD4, T y B vírgenes; aumento de TCD8; NK normales. Se sospechó el diagnóstico de síndrome de Wiskott-Aldrich. Mediante estudios de genética se identificó la mutación c.295C>T en el gen WAS. CONCLUSIONES: El caso aquí expuesto expresó una nueva mutación en el gen SWA, caracterizado por manifestaciones clínicas de fenotipo leve del síndrome de Wiskott-Aldrich, con trombocitopenia, plaquetas de tamaño normal y herencia ligada al cromosoma X. Es importante establecer el diagnóstico y tratamiento oportunos para ofrecer una mejor calidad de vida en estos pacientes.
Assuntos
Eczema , Sepse , Trombocitopenia , Síndrome de Wiskott-Aldrich , Humanos , Masculino , Mutação , Qualidade de Vida , Trombocitopenia/genética , Síndrome de Wiskott-Aldrich/diagnóstico , Síndrome de Wiskott-Aldrich/genética , Proteína da Síndrome de Wiskott-Aldrich/genética , Pré-EscolarRESUMO
Background: Little is known about the relationship of atopic dermatitis (AD) severity, phenotype, and persistence on different types of skin infections. Objective: To evaluate the relationship of AD characteristics and skin infections over time in adults. Methods: We performed a prospective dermatology practice-based study (n = 559). History of infection was assessed using questionnaires. AD severity was evaluated using Scoring Atopic Dermatitis (SCORAD), Eczema Area and Severity Index (EASI), Investigator's Global Assessment (IGA), and Patient-reported Global Assessment (PtGA). Results: At baseline, 160 (21.4%) patients reported history of ≥1 skin infection, including 14.3% with bacterial infections. In multivariable repeated measures logistic regression models, ≥1 cutaneous infection was associated with moderate (adjusted odds ratio [95% confidence interval]: 2.67 [1.67-4.28]) and severe (6.35 [3.36-12.01]) versus mild SCORAD; as well as severe SCORAD-itch; moderate and severe versus clear-mild EASI; moderate and severe versus clear-mild PtGA; mild, moderate, and severe versus clear-almost clear IGA. Cutaneous infections were not associated with ichthyosis, palmar hyperlinearity, nummular eczema, cheilitis, or hand eczema. Specific infections varied by AD severity and body site. Persistent moderate-severe disease was associated with higher odds of skin infection. Conclusion: Skin infections were associated with AD severity but not phenotype, and may be mitigated by improved AD severity.
Assuntos
Dermatite Atópica , Dermatomicoses , Eczema , Humanos , Dermatite Atópica/epidemiologia , Estudos Prospectivos , Índice de Gravidade de Doença , Imunoglobulina ARESUMO
BACKGROUND: Hand eczema (HE) is a highly prevalent, recurrent, and multifactorial disease. It encompasses a group of eczematous diseases that affect the hands, etiologically classified into irritant contact dermatitis (ICD), allergic contact dermatitis (ACD) and atopic dermatitis (AD). Few epidemiological studies in Latin America have investigated the characteristics of patients with this condition and the origin of the disease. OBJECTIVES: To analyze the profile of patients diagnosed with HE submitted to patch tests aiming to determine its etiology. METHODS: A retrospective descriptive study was carried out on epidemiological data and patch tests of patients with HE treated at a tertiary hospital in the city of São Paulo from January 2013 to December 2020. RESULTS: A total of 173 patients were studied, whose final diagnosis was 61.8% of ICD, 23.1% of ACD and 5.2% of AD, with diagnostic overlap in 42.8% of the cases. The main positive and relevant patch tests were: Kathon CG (42%), nickel sulfate (33%), and thiuram mix (18%). STUDY LIMITATIONS: The number of treated cases and socioeconomic profile was limited to a vulnerable population group. CONCLUSION: HE is a diagnosis in which overlapping etiologies are frequent, with the main sensitizers identified in ACD being Kathon CG, nickel sulfate and thiuram mix.
Assuntos
Dermatite Alérgica de Contato , Dermatite Atópica , Dermatite Irritante , Eczema , Humanos , Estudos Retrospectivos , Tiram , Testes do Emplastro , Brasil/epidemiologia , Dermatite Alérgica de Contato/diagnóstico , Dermatite Alérgica de Contato/epidemiologia , Dermatite Alérgica de Contato/etiologia , Eczema/diagnóstico , Eczema/epidemiologia , Eczema/induzido quimicamente , Dermatite Atópica/diagnóstico , Dermatite Atópica/epidemiologia , Dermatite Irritante/diagnóstico , Dermatite Irritante/epidemiologia , Dermatite Irritante/etiologia , Alérgenos/efeitos adversosRESUMO
Atopic dermatitis (AD) is a common chronic skin disease. Although generally thought to be a disease of T-cell dysregulation, recent studies have suggested that immune dysregulation of NK cells is also important. Killer cell Ig-like receptors (KIRs) are involved with NK cell regulation. The Pediatric Eczema Elective Registry is a U.S. nationwide longitudinal cohort with up to 10 y of follow-up in which 655 children had DNA available for full allelic KIR sequencing. Every 6 mo, AD activity was reported by Pediatric Eczema Elective Registry children. Using generalized estimating equations, we evaluated the association of KIR allelic variation in concert with known HLA binding ligands and whether the child reported AD in "remission" (no skin lesions and not using AD medication). KIR2DS4*001:01 (odds ratio 0.53, 95% CI [0.32, 0.88]) and KIR2DL4*001:02 (0.54, [0.33, 0.89]) in the presence of C*04:01 had the largest effect on decreasing the likelihood of AD remission. The haplotype KIR 2DL4*001:02 â¼ 2DS4*001:01 â¼ 3DL2*002:01 (0.77, [0.60, 0.99]) was also associated with a decreased likelihood of AD remission. Our findings add to the general body of evidence of a growing literature on the importance of NK cells with respect to the immunopathogenesis and natural history of AD.
Assuntos
Dermatite Atópica , Eczema , Humanos , Criança , Dermatite Atópica/genética , Receptores KIR/genética , Haplótipos , Células Matadoras NaturaisRESUMO
BACKGROUND: Hereditary actin-related protein 2/3 complex subunit 1B deficiency is characterized clinically by ear, skin, and lung infections, bleeding, eczema, food allergy, asthma, skin vasculitis, colitis, arthritis, short stature, and lymphadenopathy. OBJECTIVE: We aimed to describe the clinical, laboratory, and genetic features of six patients from four Mexican families. METHODS: We performed exome sequencing in patients of four families with suspected actinopathy, collected their data from medical records, and reviewed the literature for reports of other patients with actin-related protein 2/3 complex subunit 1B deficiency. RESULTS: Six patients from four families were included. All had recurrent infections, mainly bacterial pneumonia, and cellulitis. A total of 67% had eczema whereas 50% had food allergies, failure to thrive, hepatomegaly, and bleeding. Eosinophilia was found in all; 84% had thrombocytopenia, 67% had abnormal-size platelets and anemia. Serum levels of IgG, IgA, and IgE were highly increased in most; IgM was normal or low. T cells were decreased in 67% of patients, whereas B and NK cells were increased in half of patients. Two of the four probands had compound heterozygous variants. One patient was successfully transplanted. We identified 28 other patients whose most prevalent features were eczema, recurrent infections, failure to thrive, bleeding, diarrhea, allergies, vasculitis, eosinophilia, platelet abnormalities, high IgE/IgA, low T cells, and high B cells. CONCLUSION: Actin-related protein 2/3 complex subunit 1B deficiency has a variable and heterogeneous clinical spectrum, expanded by these cases to include keloid scars and Epstein-Barr virus chronic hepatitis. A novel deletion in exon 8 was shared by three unrelated families and might be the result of a founder effect.