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PurposeImmunoglobulin replacement therapy remains a cornerstone of treatment in antibody deficiencies and other inborn errors of immunity. While patient preferences between subcutaneous and intravenous immunoglobulin have been studied through questionnaires, no study has yet explored patient perspectives in a free environment. Therefore, we aimed to conduct a sentiment analysis as well as a temporal and geographical analysis on public opinions obtained from social media to better understand patient satisfaction and public perception on immunoglobulin therapy.MethodsA dataset of 43,700 tweets spanning from the 1st of January of 2012 to the 31st of December of 2022 was obtained. A Valence Aware Dictionary for Sentiment Reasoning sentiment analysis was performed, followed by statistical, geographical and temporal analyses.ResultsMean polarity of intravenous immunoglobulin related tweets was 0.1295 (positive), while mean polarity for subcutaneous immunoglobulin was 0.2117 (positive). Temporal analysis through a statistical model demonstrated that the volume of tweets increased over time for both subcutaneous and intravenous treatment. Geographical analysis revealed that the majority of texts originated from the United States. The highest mean polarity was observed in Romania with a mean value of 0.2966, while the lowest polarity was documented in Norway with a mean of -0.0211.ConclusionTweets linked to subcutaneous immunoglobulin treatment had a higher average polarity, indicating a more positive public perception. The amount of tweets relating to both therapies showed a tendency to increase as the years progressed, implying an increase in public discussion on immunoglobulin treatment.

Purpose: Immunoglobulin replacement therapy remains a cornerstone of treatment in antibody deficiencies and other inborn errors of immunity. While patient preferences between subcutaneous and intravenous immunoglobulin have been studied through questionnaires, no study has yet explored patient perspectives in a free environment. Therefore, we aimed to conduct a sentiment analysis as well as a temporal and geographical analysis on public opinions obtained from social media to better understand patient satisfaction and public perception on immunoglobulin therapy. Methods: A dataset of 43,700 tweets spanning from the 1st of January of 2012 to the 31st of December of 2022 was obtained. A Valence Aware Dictionary for Sentiment Reasoning sentiment analysis was performed, followed by statistical, geographical and temporal analyses. Results: Mean polarity of intravenous immunoglobulin related tweets was 0.1295 (positive), while mean polarity for subcutaneous immunoglobulin was 0.2117 (positive). Temporal analysis through a statistical model demonstrated that the volume of tweets increased over time for both subcutaneous and intravenous treatment. Geographical analysis revealed that the majority of texts originated from the United States. The highest mean polarity was observed in Romania with a mean value of 0.2966, while the lowest polarity was documented in Norway with a mean of -0.0211. Conclusion: Tweets linked to subcutaneous immunoglobulin treatment had a higher average polarity, indicating a more positive public perception. The amount of tweets relating to both therapies showed a tendency to increase as the years progressed, implying an increase in public discussion on immunoglobulin treatment. [ABSTRACT FROM AUTHOR]

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.

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. [ABSTRACT FROM AUTHOR]

Las inmunodeficiencias primarias son enfermedades genéticas caracterizadas, en la mayoría de los casos, por la predisposición del individuo afectado a infecciones recurrentes o graves con afectación de su calidad de vida. Las más frecuentes son las de defectos en la producción de anticuerpos. Cuando no se hace un diagnóstico y tratamiento oportunos puede ocurrir daño permanente a órganos blanco afectando aún más la calidad de vida. Objetivo: evaluar la calidad de vida de los pacientes con inmunodeficiencias primarias por defectos en la producción de anticuerpos y compararla con la de controles sanos. Material y métodos: estudio transversal analítico mediante la aplicación del instrumento “Pediatric Quality of Life Inventory” (Peds- QL) en su versión validada en español mexicano. La diferencia del puntaje de PedsQL entre niños con inmunodeficiencias primarias y controles sanos se determinó por la prueba de t de Student. El efecto del retraso en el diagnóstico fue evaluado por el modelo de análisis de covarianza. Se incluyeron 28 pacientes. La mediana de edad fue 5 años y 5 meses. Resultados: el promedio de edad al diagnóstico fue de 6 años con 3 meses. La mediana de retraso diagnóstico fue de 3 años 3 meses. El promedio de calidad de vida en los pacientes fue de 74.1 (DE ± 13.8) y de 83.3 (DE ± 10.1) para los controles (p = 0.005). La relación entre calidad de vida, retraso diagnóstico y presencia de complicaciones se analizó mediante un modelo lineal que fue marginalmente significativo (p = 0.056). Se encontró correlación negativa entre concentraciones de IgG en el último año y la calidad de vida. Se observó que, en los pacientes que presentaban bronquiectasias, conforme aumentan los años de retraso en el diagnóstico la calidad de vida disminuye de forma significativa (p = 0.007). Conclusiones: consideramos necesario evaluar la calidad de vida para conocer el estado de salud de los pacientes con inmunodeficiencias primarias y para su seguimiento durante el tratamiento con el objeto de incidir no sólo en la reducción del número de infecciones, hospitalizaciones y complicaciones, sino también en la mejoría de su calidad de vida. Deberá diseñarse un instrumento específico para evaluar la calidad de vida de los pacientes con inmunodeficiencias primarias.

Le agradecemos por darnos la oportunidad de contestar a la carta “Magnitud del tamaño del efecto y su importancia en la investigación pediátrica”1 del Dr. Tomás Caycho. También quisiéramos agradecer por las observaciones y comentarios del Dr. Caycho, a través de los cuales se señala la importancia y necesidad de reportar tamaño de efecto en los resultados de análisis estadístico en las investigaciones y de nuestro trabajo: “Calidad de vida de los pacientes con inmunodeficiencias primarias de anticuerpos”2 publicado en esta revista.

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.

Mutations in the genes coding for cytokines, receptors, second messengers, and transcription factors of interferon gamma (IFN-γ) immunity cause Mendelian susceptibility to mycobacterial disease (MSMD). We report the case of a 7-year-old male patient with partial dominant (PD) IFN-γ receptor 1 deficiency who had suffered from multifocal osteomyelitis attributable to bacille Calmette–Guérin vaccination since the age of 18 months. He developed hemophagocytic lymphohistiocytosis (HLH), a hyper-inflammatory complication, and died with multiorgan dysfunction, despite having been diagnosed and treated relatively early. Patients with PD IFN-γR1 deficiency usually have good prognosis and might respond to human recombinant subcutaneous IFN-γ. Several monogenic congenital defects have been linked to HLH, a catastrophic “cytokine storm” that is usually ascribed to lymphocyte dysfunction and thought to be triggered by interferon gamma. This is the sixth patient with both MSMD and HLH of whom we are aware. The fact that patients with macrophages that cannot respond to IFN-γ still develop HLH, bring these assumptions into question.

OBJECTIVE: To investigate the association between family history (FH) of neoplasia, gyneco-obstetric factors and breast cancer (BC) in a case--control study. In cases, to analyze those variables in relation with early onset of BC, the manner of detection (self-examination, prompted by pain, or casual), the size of tumor, and the elapsed time to seek medical attention. MATERIAL AND METHODS: Data from 151 prevalent BC cases and 235 age-matched controls were analyzed by multiple logistic regression, to assess the influence of BC risk factors. RESULTS: Ten per cent of patients and 1% of controls had first-degree relatives (FDR) with BC. Family history of FDR with BC (OR, 11.2; 95% CI 2.42-51.92) or with gastric or pancreatic cancer (OR, 17.7; 95% CI 2.2-142.6) was associated with BC risk. Breastfeeding at or under 25 years of age was protective against BC (OR, 0.40; 95% CI 0.24-0.66). The manner of tumor detection did not influence its size at the time of diagnosis. CONCLUSIONS: Our study confirms that FH of BC and/or of gastric or pancreatic carcinoma are risk factors for BC, while lactation at 25 years of age or earlier is protective.OBJETIVO: Investigar la asociación entre la historia familiar de neoplasias, factores ginecobstétricos y cáncer mamario (CM) en un estudio de casos y controles. Además, en los casos, estudiar estas variables en relación con inicio temprano del cáncer, forma de detección (autoexamen, exploración individual por dolor o casual), tamaño del tumor. MATERIAL E MÉTODOS: Entre enero y marzo de 1997 se estudiaron 151 casos prevalentes de CM y 235 controles pareados por edad provenientes del Hospital de Especialidades del Centro Médico del Noreste, Instituto Mexicano del Seguro Social, o del Hospital Universitario de la Universidad Autónoma de Nuevo León, ambos localizados en Monterrey, México. Los factores de riesgo se analizaron con regresión logística múltiple. RESULTADOS: Diez por ciento de casos y 1% de controles tuvieron historia familiar de primer grado para CM; este antecedente (razón de momios --RM, 11.2; IC 95%; 2.42-51.92) y el de carcinoma gástrico o pancreático (RM, 17.7; IC 95%; 2.2-142.6) se asociaron con riesgo de CM. El amamantar a los 25 años o menos fue factor protector (RM, 0.40; IC 95%; 0.24-0.66). La forma de detección del tumor no influyó en el tamaño del tumor al momento del diagnóstico. CONCLUSIONES: Se mostró que la historia familiar de CM y de carcinoma gástrico o pancreático son factores de riesgo para CM, mientras que la lactancia a los 25 años o antes, es protectora.

OBJECTIVE: To investigate the association between family history (FH) of neoplasia, gyneco-obstetric factors and breast cancer (BC) in a case--control study. In cases, to analyze those variables in relation with early onset of BC, the manner of detection (self-examination, prompted by pain, or casual), the size of tumor, and the elapsed time to seek medical attention. MATERIAL AND METHODS: Data from 151 prevalent BC cases and 235 age-matched controls were analyzed by multiple logistic regression, to assess the influence of BC risk factors. RESULTS: Ten per cent of patients and 1% of controls had first-degree relatives (FDR) with BC. Family history of FDR with BC (OR, 11.2; 95% CI 2.42-51.92) or with gastric or pancreatic cancer (OR, 17.7; 95% CI 2.2-142.6) was associated with BC risk. Breastfeeding at or under 25 years of age was protective against BC (OR, 0.40; 95% CI 0.24-0.66). The manner of tumor detection did not influence its size at the time of diagnosis. CONCLUSIONS: Our study confirms that FH of BC and/or of gastric or pancreatic carcinoma are risk factors for BC, while lactation at 25 years of age or earlier is protective.