JAGN1 Deficient Severe Congenital Neutropenia: Two Cases from the Same Family.

Recently autosomal recessively inherited mutations in the gene encoding Jagunal homolog 1 (JAGN1) was described as a novel disease-causing gene of severe congenital neutropenia (SCN) JAGN1-mutant neutrophils were characterized by abnormality in endoplasmic reticulum structure, absence of granules, abnormal N-glycosylation of proteins and susceptibility to apoptosis. These findings imply the role of JAGN1 in neutrophil survival. Here, we report two siblings with a homozygous mutation in JAGN1 gene, exhibiting multisystemic involvement.

Long-Term Effect of Sublingual and Subcutaneous Immunotherapy in Dust Mite-Allergic Children With Asthma/Rhinitis: A 3-Year Prospective Randomized Controlled Trial.

BACKGROUND AND OBJECTIVE: Specific allergen immunotherapy is the only treatment modality that might change the natural course of allergic diseases in childhood. We sought to prospectively compare the long-term clinical and immunological effects of sublingual (SLIT) and subcutaneous (SCIT) immunotherapy compared with pharmacotherapy alone. METHODS: In this single-center, prospective randomized controlled trial, 48 children with mild persistent asthma with/without rhinitis, monosensitized to house dust mites (HDMs) were followed for 3 years. At baseline and years 1 and 3 of follow-up, patients were evaluated and compared for total rhinitis (TRSS) and asthma (TASS) symptom scores, total symptom scores (TSS), total medication scores (TMS), safety profiles, skin-nasal-bronchial reactivity, and immunological parameters. RESULTS: A significant reduction was observed in TASS for both HDM-SCIT and HDM-SLIT at year 3 of treatment compared with baseline and controls (P<.05 for both), with significant improvement in rhinitis symptoms for both groups compared with controls (P=.01 for both). TSS decreased significantly in both HDM-SCIT and HDM-SLIT at year 3 compared with baseline (P=.007 and P=.04, respectively) and controls (P<.01 for both). A significant reduction in TMS was observed in HDM-SCIT and HDM-SLIT compared with baseline and controls (P=.01 in all cases), with a reduction in skin reactivity to HDM (P<.05). Finally, a significant increase in allergen specific IgG4 was observed in the SCIT group at year 3 compared with baseline, the SLIT group, and controls (P<.001 in all cases). CONCLUSIONS: HDM-sensitized asthmatic children treated for at least 3 years with either SCIT or SLIT showed sustained clinical improvement.

Long-term effect of sublingual and subcutaneous immunotherapy in dust mite–allergic children with asthma/rhinitis: a 3-year prospective randomized controlled trial

Background and Objective: Specific allergen immunotherapy is the only treatment modality that might change the natural course of allergic diseases in childhood. We sought to prospectively compare the long-term clinical and immunological effects of sublingual (SLIT) and subcutaneous (SCIT) immunotherapy compared with pharmacotherapy alone. Methods: In this single-center, prospective randomized controlled trial, 48 children with mild persistent asthma with/without rhinitis, monosensitized to house dust mites (HDMs) were followed for 3 years. At baseline and years 1 and 3 of follow-up, patients were evaluated and compared for total rhinitis (TRSS) and asthma (TASS) symptom scores, total symptom scores (TSS), total medication scores (TMS), safety profiles, skin-nasal-bronchial reactivity, and immunological parameters. Results: A significant reduction was observed in TASS for both HDM-SCIT and HDM-SLIT at year 3 of treatment compared with baseline and controls (P<.05 for both), with significant improvement in rhinitis symptoms for both groups compared with controls (P=.01 for both). TSS decreased significantly in both HDM-SCIT and HDM-SLIT at year 3 compared with baseline (P=.007 and P=.04, respectively) and controls (P<.01 for both). A significant reduction in TMS was observed in HDM-SCIT and HDM-SLIT compared with baseline and controls (P=.01 in all cases), with a reduction in skin reactivity to HDM (P<.05). Finally, a significant increase in allergen specific IgG4 was observed in the SCIT group at year 3 compared with baseline, the SLIT group, and controls (P<.001 in all cases). Conclusions: HDM-sensitized asthmatic children treated for at least 3 years with either SCIT or SLIT showed sustained clinical improvement (AU)

Antecedentes: La inmunoterapia con alérgenos es el único tratamiento que podría cambiar el curso natural evolutivo de las enfermedades alérgicas en la infancia. Nuestro objetivo era comparar, de manera prospectiva, la eficacia a largo plazo de la inmunoterapia sublingual (SLIT) y subcutánea (SCIT), con el tratamiento exclusivo con farmacoterapia convencional. Métodos:En este ensayo clínico, prospectivo de tres años de duración, realizado en un solo centro y aleatorizado, se incluyeron 48 niños con asma leve persistente, con o sin rinitis asociada, monosensibilizados a los ácaros del polvo (HDM). Los pacientes fueron evaluados al inicio, al año y a los tres años de tratamiento, comparándose los cambios en la puntuación de síntomas nasales (TRSS), bronquiales (TASS), puntuación total de síntomas (TSS) y consumo de medicación (TMS), perfil de seguridad, reactividad frente al alérgeno cutánea, nasal y bronquial y diversos parámetros inmunológicos. Resultados: Se observó una reducción significativa del TASS tanto para el grupo HDM-SCIT como HDM-SLIT al final del tercer año de tratamiento, tanto cuando se comparaba con la situación basal como con los cambios observados en el grupo control (p<0.05, respectivamente). El TRSS también mejoró significativamente en ambos grupos HDM-SCIT y HDM-SLIT en el tercer año de tratamiento, cuando los cambios se compararon con los observados en el grupo control (p=0,01, en ambos). El TSS y el TMS disminuyeron también significativamente en ambos grupos HDM-SCIT y HDM-SLIT en el tercer año, comparado con la situación basal (p=0,007, p=0,04/ p=0,01, p=0,01 respectivamente) y con el grupo control (p<0,01,p<0,01/ p=0,01, p=0,01, respectivamente). Tras tres años de tratamiento la reactividad cutánea frente a los alérgenos de los ácaros disminuyó significativamente (p<0,05). Los niveles de IgG4 específica frente a ácaros se incrementaron en el grupo SCIT-HDM, comparados con la situación basal y con los cambios observados en el grupo SLIT-HDM y control (p<0,001, respectivamente). Conclusiones: El tratamiento durante tres años con inmunoterapia específica tanto SCIT como SLIT se acompañó de una eficacia clínica sostenida, en este grupo de niños asmáticos sensibilizados a los ácaros del polvo. Ambas rutas de administración de la inmunoterapia parecen tener mecanismos de acción similares (AU)

Alteration in humoral immunity is common among family members of patients with common variable immunodeficiency.

BACKGROUND: The prevalence of primary immunodeficiency (PID) in the relatives of patients with common variable immunodeficiency (CVID) and IgA deficiency is high. Allergic disorders have been recorded in patients with humoral immunodeficiency. We aimed to determine the frequency of humoral immunodeficiency and atopy in the relatives of patients with CVID. METHODS: The study population comprised 20 CVID patients and their relatives. All relatives were screened using a questionnaire covering demographic characteristics, warning signs of PID (adults and children), and core questions on asthma, rhinitis, and eczema from the International Study of Asthma and Allergies in Childhood (ISAAC). We also recorded absolute neutrophil and lymphocyte counts, serum immunoglobulin levels, pulmonary function values, and skin prick test results. RESULTS: The study sample comprised 20 patients with CVID (15 males, 5 females; mean (SD] age, 16.4 (9] years) and 63 first-degree relatives (18 mothers, 16 fathers, 16 sisters, 10 brothers, and 3 offspring). The rate of parental consanguinity was 75%. Of 17 family members with positive PID warning signs, 6 had concomitant hypogammaglobulinemia (3 low IgM levels, 2 selective IgA deficiency, and 1 partial IgA deficiency). The ISAAC questionnaire revealed allergic rhinitis in 3 mothers, asthma in 2 fathers, and 1 sibling. Skin prick testing revealed sensitization to aeroallergens in 31.6% of cases in addition to 1 parent and 1 sibling. CONCLUSIONS: Almost half of the 20 families with a CVID patient had at least 1 additional member with hypogammaglobulinemia, leading us to recommend routine screening for relatives of CVID patients.

Alteration in humoral immunity is common among family members of patients with common variable immunodeficiency

Background: The prevalence of primary immunodeficiency (PID) in the relatives of patients with common variable immunodeficiency (CVID) and IgA deficiency is high. Allergic disorders have been recorded in patients with humoral immunodeficiency. We aimed to determine the frequency of humoral immunodeficiency and atopy in the relatives of patients with CVID. Methods: The study population comprised 20 CVID patients and their relatives. All relatives were screened using a questionnaire covering demographic characteristics, warning signs of PID (adults and children), and core questions on asthma, rhinitis, and eczema from the International Study of Asthma and Allergies in Childhood (ISAAC). We also recorded absolute neutrophil and lymphocyte counts, serum immunoglobulin levels, pulmonary function values, and skin prick test results. Results: The study sample comprised 20 patients with CVID (15 males, 5 females; mean [SD] age, 16.4 [9] years) and 63 first-degree relatives (18 mothers, 16 fathers, 16 sisters, 10 brothers, and 3 offspring). The rate of parental consanguinity was 75%. Of 17 family members with positive PID warning signs, 6 had concomitant hypogammaglobulinemia (3 low IgM levels, 2 selective IgA deficiency, and 1 partial IgA deficiency). The ISAAC questionnaire revealed allergic rhinitis in 3 mothers, asthma in 2 fathers, and 1 sibling. Skin prick testing revealed sensitization to aeroallergens in 31.6% of cases in addition to 1 parent and 1 sibling. Conclusions: Almost half of the 20 families with a CVID patient had at least 1 additional member with hypogammaglobulinemia, leading us to recommend routine screening for relatives of CVID patients (AU)

Antecedentes: Es conocida la alta prevalencia de inmunodeficiencias entre los familiares de pacientes con inmunodeficiencia común variable (IDCV) y con déficit de IgA. Por otro lado, también se han descrito enfermedades alérgicas en pacientes con inmunodeficiencias humorales. El objetivo de este estudio ha sido el determinar la frecuencia de inmunodeficiencias humorales y de atopia entre los familiares de pacientes con IDCV. Métodos: Se estudiaron familiares de pacientes con IDCV. Todos los miembros de la familias fueron seleccionadas por un cuestionario que incluyó la determinación de las características demográficas, las señales de alarma, en adultos y niños, de padecer inmunodeficiencias primarias (IDP) y preguntas del Estudio Internacional de Asma y Alergia en la Infancia (ISAAC) para el asma, la rinitis y el eczema. Además, se realizaron estudios analíticos sobre el contaje de neutrófilos y linfocitos, los niveles de inmunoglobulinas séricas, la función pulmonar y pruebas cutáneas prick. Resultados: Se determinaron veinte casos de IDCV (15M, 5F, edad media: 16,4 ± 9 años) y se estudiaron un total de 63 parientes de primer grado (18 madres, 16 padres, 16 hermanas, 10 hermanos y 3 descendientes). La tasa de consanguinidad de los padres fue de 75%. En general, entre los 17 miembros de la familia con señales de alarma de padecer IDP, 6 tenían hipogammaglobulinemia concomitante; 3 bajos niveles de IgM, 2 selectivos y 1 con parcial déficit de IgA. El cuestionario ISAAC reveló rinitis alérgica en 3/18 de las madres; mientras que, el asma, en 2/18, de padres y de 1/26 de los hermanos. Finalmente, en las pruebas de punción cutánea se obtuvo una sensibilización a aeroalérgenos en el 31,6% de los casos, pero en ninguno de sus padres, hermanos o descendientes. Conclusiones: En 20 familias de pacientes con IDCV, casi la mitad de sus miembros tenían al menos un individuo con hipogammaglobulinemia, por lo que recomendamos una exploración rutinaria entre todos los familiares de pacientes con IDCV(AU)

Vitamin D as an adjunct to subcutaneous allergen immunotherapy in asthmatic children sensitized to house dust mite.

BACKGROUND: We aimed to investigate the efficacy, safety, and T regulatory cell response of vitamin D as an adjunct to allergen-specific immunotherapy (IT). METHODS: Fifty children with asthma and receiving pharmacotherapy were randomized into three groups as: subcutaneous IT (SCIT) along with vitamin D supplementation (650 U/day; n: 17), SCIT alone (n: 15), and pharmacotherapy alone (n: 18). All patients were evaluated at baseline, 6th and 12th months for scorings of symptoms and medication, skin prick testing, total IgE, specific IgE, and Der p 1-specific IgG4. In addition, D. pteronyssinus-induced CD4(+) CD25(+) FOXP3(+) T regulatory cell percentage, intracellular Foxp3 expression, and peripheral blood mononuclear cell IL-10 and TGF-ß responses were assessed. RESULTS: In the SCIT + vitamin D and SCIT alone groups, total asthma symptom score (TASS), total symptom score (TSS), and total medication scores (TMS) were significantly lower than pharmacotherapy group at the end of 1 year. While the comparison of delta values (Δ 6th and Δ 12th month - baseline) of those scores revealed no significant differences between the two IT groups, TASS at the 6th month was lower in the SCIT + vitamin D group compared with others. There was a significant and positive trend in the levels of Der p 1-specific IgG4 in both IT groups throughout the study period. Whereas the levels of Der p 1-induced IL-10 and TGF-ß were similar between IT groups, the mean fluorescence intensity of Foxp3 was highest in the SCIT + vitamin D group compared with others at the 12th month. The rate of discontinuation of inhaled corticosteroid (ICS) was 6/17 in SCIT + vitamin D, 3/15 in SCIT, and 0/18 in the pharmacotherapy group (P = 0.02). CONCLUSION: Both SCIT groups fared better than pharmacotherapy alone at the end of 1 year. Although the clinical and immunologic outcomes were mostly similar between the two IT groups, some favorable outcomes of vitamin D warrant further investigation in more selected populations with varying doses as adjunct to IT.

Efficacy of intravenous immunoglobulin treatment in children with common variable immunodeficiency.

BACKGROUND: Children with common variable immunodeficiency (CVID) have increased susceptibility to infections. OBJECTIVE: We evaluated the role of intravenous immunoglobulin (IVIG) replacement therapy on the clinical outcome of patients with CVID. METHODS: We studied children diagnosed with CVID and treated with IVIG (500 mg/kg every 3 weeks). RESULTS: The study population comprised 29 children with CVID (mean [SD] age, 11.8 [6.1] years) with at least 1 year of follow-up before IVIG replacement therapy. Mean follow-up duration was 5.6 (3.5) years (range, 15 months-14 years). During therapy, median serum IgG levels increased from 410 to 900 mg/dL. The mean number of respiratory infections per patient per year decreased significantly from 10.2 to 2.5. The annual number and length of hospital stays decreased significantly from 1.36 to 0.21 and 16.35 to 6.33 days per patient, respectively. The mean annual number of antibiotics used decreased significantly from 8.27 to 2.50 per patient. Twelve patients had developed bronchiectasis before initiation of IVIG; 3 patients were cured of this condition. Age at diagnosis, diagnostic delay, number of respiratory tract infections, and number of antibiotics were found to be significantly higher in patients with bronchiectasis, as was lower B-cell percentage. However, gastrointestinal involvement due to noninfectious causes did not improve significantly after IVIG replacement therapy. CONCLUSION: CVID patients treated with IVIG (500 mg/kg every 3 weeks) had satisfactory serum IgG levels, fewer respiratory tract infections, fewer and shorter hospital stays, and reduced antibiotic usage. However, no effect on gastrointestinal involvement was observed. Early IVIG replacement therapy is important in preventing bronchiectasis.