RESUMEN
Mycophenolate mofetil (MMF) is an immunosuppressive drug used for the treatment of autoimmune rheumatological diseases. To test the risk of hypothetical drug-induced hypogammaglobulinemia, the aim of this study was to report the trend of the immunoglobulin (Ig) values and of the infectious diseases in children treated with MMF. This study retrospectively evaluated demographic, clinical, and laboratory data of a cohort of patients affected by a chronic rheumatic disease receiving MMF, followed at the Rheumatology Unit of Meyer Children Hospital, Florence. A total of 29 pediatric patients were enrolled. In patients with normal values of immunoglobulins at the baseline, treatment with MMF resulted in a statistically significant reduction of the IgG levels (p = 0.0058) and in a decrease of IgM levels not reaching statistical significance. The levels of IgA were not affected. During the follow-up, seven patients developed an humoral immune defect. The univariate analysis did not identify any risk factors related to the iatrogenic hypogammaglobulinemia. The infection rate during MMF therapy was significantly higher than the 12-month period before therapy (p = 0.006), while the severe infections did not significantly increase (p = 0.1818), even considering only the patients with hypogammaglobulinemia. CONCLUSION: In pediatric patients with chronic rheumatic diseases, immunological first level tests and serological analyses to screen the protection against the common childhood pathogens are suggested before starting an immunosuppressive drug. These patients should also complete the vaccination schedule. In patients treated with MMF a strict monitoring of Ig is required during treatment and after discontinuation of the drug. WHAT IS KNOWN: ⢠MMF is an immunosuppressive drug initially used for the treatment of the graft-versus-host disease. ⢠Mycophenolic acid is an inhibitor of inosine-5'-monophosphate dehydrogenase, expressed in lymphocytes; therefore, MMF could impair the immune system function. WHAT IS NEW: ⢠MMF resulted in a reduction of IgG and an increase of not severe infection rate. ⢠Immunological first level tests, including Ig, lymphocyte subpopulations, and antibody response to vaccines, are suggested in pediatric patients before starting MMF; a strict monitoring of Ig is important before, during, and after MMF treatment.
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Agammaglobulinemia , Ácido Micofenólico , Agammaglobulinemia/inducido químicamente , Agammaglobulinemia/tratamiento farmacológico , Niño , Susceptibilidad a Enfermedades/inducido químicamente , Humanos , Inmunoglobulina G , Inmunosupresores/efectos adversos , Ácido Micofenólico/efectos adversos , Estudios RetrospectivosRESUMEN
AIM: To estimate hospitalisation rate and investigate the role of age, prematurity and vaccination status in severe pertussis cases. METHODS: We retrospectively evaluated 200 children aged 0-14 years, admitted to the emergency rooms of Meyer Hospital of Florence and Pisa Hospital with a diagnosis of pertussis from 1 October 2010 to 31 January 2020. RESULTS: Children younger than 12 months were 63.0%. Preterm infants were 6.5%. The rate of hospitalisation was 49.0%. Among hospitalised cases, 80.6% were younger than 5 months. Overall, 62.0% were unvaccinated; this percentage increased among hospitalised (73.5%) and preterm subsamples (76.9%). Delays in pertussis vaccination were found in 57.7% of term infants and in 80.0% of preterms. Multivariable analysis confirmed the age under 2 months as the variable at higher risk for hospitalisation (OR 4.49, 95% CI 1.85-10.96, p < 0.001). Being fully vaccinated represented a significant protective factor (OR 0.12, 95% CI 0.04-0.35, p < 0.001). CONCLUSION: Older classes of age and a complete vaccination, in time with the recommended schedule, are both protective factors for hospitalisation in severe pertussis disease. The widespread vaccination delay frequently observed in preterm children may be the cause for their higher rate of hospitalisation.
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Tos Ferina , Niño , Humanos , Lactante , Recién Nacido de Bajo Peso , Recién Nacido , Recien Nacido Prematuro , Vacuna contra la Tos Ferina , Estudios Retrospectivos , Vacunación , Tos Ferina/epidemiología , Tos Ferina/prevención & controlRESUMEN
Medical advances have dramatically improved the long-term prognosis of children and adolescents with inborn errors of immunity (IEIs). Transfer of the medical care of individuals with pediatric IEIs to adult facilities is also a complex task because of the large number of distinct disorders, which requires involvement of patients and both pediatric and adult care providers. To date, there is no consensus on the optimal pathway of the transitional care process and no specific data are available in the literature regarding patients with IEIs. We aimed to develop a consensus statement on the transition process to adult health care services for patients with IEIs. Physicians from major Italian Primary Immunodeficiency Network centers formulated and answered questions after examining the currently published literature on the transition from childhood to adulthood. The authors voted on each recommendation. The most frequent IEIs sharing common main clinical problems requiring full attention during the transitional phase were categorized into different groups of clinically related disorders. For each group of clinically related disorders, physicians from major Italian Primary Immunodeficiency Network institutions focused on selected clinical issues representing the clinical hallmark during early adulthood.
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Enfermedades de Inmunodeficiencia Primaria/terapia , Transición a la Atención de Adultos/normas , Adulto , Edad de Inicio , Niño , Consenso , Humanos , Servicios de Información , Italia/epidemiología , Guías de Práctica Clínica como Asunto , Enfermedades de Inmunodeficiencia Primaria/diagnósticoRESUMEN
Absent pulmonary valve syndrome is a rare congenital heart disease characterized by absent or rudimentary pulmonary valve leaflets and hypoplastic pulmonary annulus. The most common variant, associated with tetralogy of Fallot, implies dilatation of pulmonary branches and usually absent ductus arteriosus. Rarely, absent pulmonary valve occurs with intact ventricular septum: pulmonary branches are normally sized or mildly dilated and ductus arteriosus is usually patent. The rarest type is associated with intact ventricular septum and tricuspid atresia. A close connection has been raised between pulmonary regurgitation and development of tricuspid valve. We describe a case of prenatal diagnosed absent pulmonary valve with intact ventricular septum and patent ductus arteriosus in which severe pulmonary regurgitation caused reversible functional atresia of tricuspid valve. Postnatally, satisfactory biventricular circulation was obtained with inotropic support for a few days while ductus arteriosus closed spontaneously. At a 3-year follow up the child is asymptomatic without therapy.
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Atresia Pulmonar/diagnóstico por imagen , Válvula Pulmonar/anomalías , Válvula Pulmonar/diagnóstico por imagen , Atresia Tricúspide/diagnóstico por imagen , Preescolar , Diagnóstico Diferencial , Humanos , Lactante , Recién Nacido , Masculino , Diagnóstico Prenatal , Ultrasonografía PrenatalRESUMEN
Knowing the incidence of invasive meningococcal disease (IMD) is essential for planning appropriate vaccination policies. However, IMD may be underestimated because of misdiagnosis or insufficiently sensitive laboratory methods. Using a national molecular surveillance register, we assessed the number of cases misdiagnosed and diagnoses obtained postmortem with real-time PCR (rPCR), and we compared sensitivity of rPCR versus culture-based testing. A total of 222 IMD cases were identified: 11 (42%) of 26 fatal cases had been misdiagnosed or undiagnosed and were reclassified as IMD after rPCR showed meningococcal DNA in all available specimens taken postmortem. Of the samples tested with both rPCR and culture, 58% were diagnosed by using rPCR alone. The underestimation factor associated with the use of culture alone was 3.28. In countries such as Italy, where rPCR is in limited use, IMD incidence may be largely underestimated; thus, assessments of benefits of meningococcal vaccination may be prone to error.
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Infecciones Meningocócicas/epidemiología , Neisseria meningitidis , Adolescente , Adulto , Niño , Preescolar , Errores Diagnósticos , Femenino , Humanos , Incidencia , Lactante , Italia/epidemiología , Masculino , Infecciones Meningocócicas/diagnóstico , Vacunas Meningococicas , Reacción en Cadena en Tiempo Real de la Polimerasa , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Purine nucleoside phosphorylase (PNP) deficiency has been recently introduced in the newborn screening program in Tuscany. In order to improve the PNP screening efficiency, we developed a 2nd tier test to quantify PNP primary markers deoxyguanosine (dGuo) and deoxyinosine (dIno). METHODS: Dried blood spots (DBS) samples were extracted with 200 µL of methanol and 100 µL of water (by two steps). Internal standards were added at a final concentration of 10 µmol/L. After extraction, samples were analysed by LC-MS/MS. The chromatographic run was performed in gradient mode by using a Synergi Fusion column. RESULTS: The assay was linear over a concentration range of 0.05-50 µmol/L (R2>0.999) for dGuo and 0.5-50 µmol/L (R2>0.998) for dIno. Intra- and interassay imprecision (mean CVs) for dIno and dGuo ranged from 2.9% to 12%. Limit of quantitaion (LOQ) were found to be 0.05 µmol/L and 0.5 µmol/L for dGuo and dIno, respectively. The reference ranges, obtained by measuring dGuo and dIno concentrations on DBS, were close to zero for both biomarkers. Moreover, DBS samples from seven patients with confirmed PNP were retrospectively evaluated and correctly identified. CONCLUSIONS: The LC-MS/MS method can reliably measure dIno and dGuo in DBS for the diagnosis of PNP. Validation data confirm the present method is characterised by good reproducibility, accuracy and imprecision for the quantitation of dIno and dGuo. The assay also appears suitable for use in monitoring treatment of PNP patients.
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Pruebas con Sangre Seca , Tamizaje Neonatal , Purina-Nucleósido Fosforilasa/deficiencia , Errores Innatos del Metabolismo de la Purina-Pirimidina/sangre , Adulto , Cromatografía Liquida , Humanos , Recién Nacido , Enfermedades de Inmunodeficiencia Primaria , Purina-Nucleósido Fosforilasa/sangre , Purina-Nucleósido Fosforilasa/metabolismo , Errores Innatos del Metabolismo de la Purina-Pirimidina/diagnóstico , Errores Innatos del Metabolismo de la Purina-Pirimidina/metabolismo , Espectrometría de Masas en TándemRESUMEN
BACKGROUND: Purine nucleoside phosphorylase (PNP) deficiency is a rare form of autosomal recessive combined primary immunodeficiency caused by a enzyme defect leading to the accumulation of inosine, 2'-deoxy-inosine (dIno), guanosine, and 2'-deoxy-guanosine (dGuo) in all cells, especially lymphocytes. Treatments are available and curative for PNP deficiency, but their efficacy depends on the early approach. PNP-combined immunodeficiency complies with the criteria for inclusion in a newborn screening program. OBJECTIVE: This study evaluate whether mass spectrometry can identify metabolite abnormalities in dried blood spots (DBSs) from affected patients, with the final goal of individuating the disease at birth during routine newborn screening. METHODS: DBS samples from 9 patients with genetically confirmed PNP-combined immunodeficiency, 10,000 DBS samples from healthy newborns, and 240 DBSs from healthy donors of different age ranges were examined. Inosine, dIno, guanosine, and dGuo were tested by using tandem mass spectrometry (TMS). T-cell receptor excision circle (TREC) and kappa-deleting recombination excision circle (KREC) levels were evaluated by using quantitative RT-PCR only for the 2 patients (patients 8 and 9) whose neonatal DBSs were available. RESULTS: Mean levels of guanosine, inosine, dGuo, and dIno were 4.4, 133.3, 3.6, and 3.8 µmol/L, respectively, in affected patients. No indeterminate or false-positive results were found. In patient 8 TREC levels were borderline and KREC levels were abnormal; in patient 9 TRECs were undetectable, whereas KREC levels were normal. CONCLUSION: TMS is a valid method for diagnosis of PNP deficiency on DBSs of affected patients at a negligible cost. TMS identifies newborns with PNP deficiency, whereas TREC or KREC measurement alone can fail.
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Síndromes de Inmunodeficiencia/diagnóstico , Mutación , Purina-Nucleósido Fosforilasa/deficiencia , Purina-Nucleósido Fosforilasa/genética , Errores Innatos del Metabolismo de la Purina-Pirimidina/diagnóstico , Adolescente , Preescolar , Reparación del ADN , Desoxiguanosina/análisis , Desoxiguanosina/metabolismo , Pruebas con Sangre Seca , Femenino , Guanosina/análisis , Guanosina/metabolismo , Humanos , Síndromes de Inmunodeficiencia/genética , Síndromes de Inmunodeficiencia/patología , Lactante , Recién Nacido , Inosina/análogos & derivados , Inosina/análisis , Inosina/metabolismo , Linfocitos/patología , Masculino , Tamizaje Neonatal , Enfermedades de Inmunodeficiencia Primaria , Errores Innatos del Metabolismo de la Purina-Pirimidina/genética , Errores Innatos del Metabolismo de la Purina-Pirimidina/patología , Espectrometría de Masas en TándemRESUMEN
BACKGROUND: Adenosine deaminase (ADA)-severe combined immunodeficiency (SCID) is caused by genetic variants that disrupt the function of ADA. In its early-onset form, it is rapidly fatal to infants. Delayed or late-onset ADA-SCID is characterized by insidious progressive immunodeficiency that leads to permanent organ damage or death. Quantification of T-cell receptor excision circles (TRECs) or tandem mass spectrometry (tandem-MS) analysis of dried blood spots (DBSs) collected at birth can identify newborns with early-onset ADA-SCID and are used in screening programs. However, it is not clear whether these analyses can identify newborns who will have delayed or late-onset ADA-SCID before symptoms appear. OBJECTIVE: We performed a retrospective study to evaluate whether tandem-MS and quantitative TREC analyses of DBSs could identify newborns who had delayed-onset ADA-SCID later in life. METHODS: We tested stored DBSs collected at birth from 3 patients with delayed-onset ADA-SCID using tandem-MS (PCT EP2010/070517) to evaluate levels of adenosine and 2'-deoxyadenosine and real-time PCR to quantify TREC levels. We also analyzed DBSs from 3 newborns with early-onset ADA-SCID and 2 healthy newborn carriers of ADA deficiency. RESULTS: The DBSs taken at birth from the 3 patients with delayed-onset ADA-SCID had adenosine levels of 10, 25, and 19 µmol/L (normal value, <1.5 µmol/L) and 2'-deoxyadenosine levels of 0.7, 2.7, and 2.4 µmol/L (normal value, <0.07 µmol/L); the mean levels of adenosine and 2'-deoxyadenosine were respectively 12.0- and 27.6-fold higher than normal values. DBSs taken at birth from all 3 patients with delayed-onset ADA deficiency had normal TREC levels, but TRECs were undetectable in blood samples taken from the same patients at the time of diagnosis. CONCLUSION: Tandem-MS but not TREC quantification identifies newborns with delayed- or late-onset ADA deficiency.
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Adenosina Desaminasa/sangre , Agammaglobulinemia/diagnóstico , Receptores de Antígenos de Linfocitos T/sangre , Inmunodeficiencia Combinada Grave/diagnóstico , Espectrometría de Masas en Tándem , Adenosina Desaminasa/deficiencia , Adenosina Desaminasa/genética , Desoxiadenosinas/metabolismo , Activación Enzimática , Eritrocitos/metabolismo , Humanos , Inmunoglobulinas/sangre , Inmunofenotipificación , Recién Nacido , Subgrupos Linfocitarios/metabolismo , Receptores de Antígenos de Linfocitos T/genética , Estudios RetrospectivosRESUMEN
Background: Hemophagocytic Lymphohistiocytosis (HLH) is a rare and life-threatening condition characterized by a severe impairment of the immune homeostasis. While Familial-HLH (FHL) is a known cause, the involvement of other Inborn Errors of Immunity (IEI) in pediatric-HLH remains understudied. Objective: This systematic review aimed to assess the clinical features, triggers, laboratory data, treatment, and outcomes of pediatric HLH patients with IEI other than FHL (IEInotFHL), emphasizing the importance of accurate identification and management. Methods: A systematic search for studies meeting inclusion criteria was conducted in PubMed, EMBASE, MEDLINE, and Cochrane Central. Quality assessment was performed through JBI criteria. Results: A comprehensive search yielded 108 records meeting inclusion criteria, involving 178 patients. We identified 46 different IEI according to IUIS 2022 Classification. Combined immunodeficiencies, immune dysregulation disorders, and phagocyte defects were the IEI most frequently associated with HLH. In 75% of cases, HLH preceded the IEI diagnosis, often with an unrecognized history of severe infections. Triggers reflected the specific infection susceptibilities within IEI groups. Liver and central nervous system involvement were less common than in FHL cases. Treatment approaches and outcomes varied, with limited long-term follow-up data, limiting the assessment of therapeutic efficacy across IEI groups. Conclusion: A comprehensive evaluation encompassing immunological, infectious, and genetic aspects is essential in pediatric-HLH. Relying solely on FHL or EBV susceptibility disorders tests is insufficient, as diverse other IEI can contribute to HLH. Early recognition of HLH as a potential warning sign can guide timely diagnostic investigations and facilitate tailored therapeutic interventions for improved outcomes. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=371425, PROSPERO, CRD42022371425.
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Enfermedades del Sistema Inmune , Linfohistiocitosis Hemofagocítica , Niño , Humanos , Susceptibilidad a Enfermedades , Homeostasis , Linfohistiocitosis Hemofagocítica/diagnóstico , Linfohistiocitosis Hemofagocítica/genética , Linfohistiocitosis Hemofagocítica/tratamiento farmacológico , Enfermedades del Sistema Inmune/diagnósticoRESUMEN
[This corrects the article DOI: 10.3389/fimmu.2024.1282804.].
RESUMEN
BACKGROUND: Inborn errors of immunity (IEIs) include 485 inherited disorders characterized by an increased susceptibility to life-threatening infectious diseases, autoimmunity, and malignant diseases with a high mortality rate in the first years of life. Severe combined immunodeficiency is the most severe of the IEIs, and its detection should be a primary goal in a newborn screening (NBS) program. The term "actionable" has recently been used for all IEIs with outcomes that can be demonstrably improved through early specialized intervention. OBJECTIVE: To evaluate the results of the expanded NBS strategy for IEIs in Tuscany Region (Italy), based on T-cell receptor excision circle, kappa recombining excision circle, and tandem mass-based assays. METHODS: This is a retrospective study collecting data from all infants born in Tuscany from October 10, 2018, to October 10, 2022. Tandem mass assay to identify adenosine deaminase and purine nucleoside phosphorylase deficiency, together with T-cell receptor excision circle and kappa recombining excision circle molecular analysis, was conducted on dried blood spot from the newborns' Guthrie Cards. A new dried blood spot and evaluation by an immunologist were carried out when the results of the first test were outside the diagnostic cutoffs. RESULTS: A total of 94,319 newborns were evaluated. Referral rates for T-cell recombining excision circles (0.031%) and kappa recombining excision circles (0.074%) in this study are in line with the data available in literature. The results from the expanded NBS strategy revealed an incidence rate of 1 per 9431 affected newborns. CONCLUSIONS: This work represents the first description of a sustainable and real-life-based expanded NBS program for IEIs with a high diagnostic incidence facilitating prompt management of identified patients.
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Tamizaje Neonatal , Humanos , Recién Nacido , Italia/epidemiología , Estudios Retrospectivos , Masculino , Femenino , Inmunodeficiencia Combinada Grave/diagnóstico , Inmunodeficiencia Combinada Grave/epidemiología , Inmunodeficiencia Combinada Grave/inmunología , Inmunodeficiencia Combinada Grave/genética , Receptores de Antígenos de Linfocitos T/genética , Receptores de Antígenos de Linfocitos T/inmunologíaRESUMEN
Background: Respiratory Syncytial Virus (RSV) is the primary cause of respiratory infections and hospitalizations in young children globally, leading to substantial disease burden and mortality. The aim of the present study was to review and provide updates on how the SARS-CoV-2 pandemic have significantly influenced RSV epidemiology on hospitalized children due to RSV infection. A potential impact of the available preventive strategies on the same population were provided. Methods: All children aged 0-6 years hospitalized at Meyer Children's Hospital IRCCS for RSV infection from September 2014 to March 2023 were retrospectively recorded. Seasonal trends before and after SARS-CoV-2 pandemic, age distribution, ICU admission and co-infections, comorbidities and prematurity were retrieved. Predictions on the number of hospitalizations avoided by the deployment of different preventive strategies were provided. Results: A total of 1,262 children with RSV infection were included in the study. The 70% of them had less than 1 year-of-age at the moment of hospitalization and almost 50% less than 3 months. In the post-pandemic seasons, a 317% increase in the number of hospitalizations was recorded with a significant increase in older children compared to the pre-pandemic seasons. ICU support was required for 22% of children, the majority of whom were under 3 months of age. Almost 16% of hospitalized children were born preterm and only 27% of hospitalized children had prior comorbidities. The rate of comorbidities among RSV hospitalized children increased with age. Nirsevimab prophylaxis could have prevented more than 46% of hospitalizations in this cohort. A preventive strategy addressing also children aged 7 months to 6 years of age with co-existing comorbidities would increase that rate above 57%. Discussion: The identification of RSV hospitalization-related features is informing the decision-maker for the deployment of the wisest preventive approach on a population scale.
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Autoinmunidad/inmunología , Linfocitos T CD4-Positivos/inmunología , Síndrome de DiGeorge/inmunología , Antígenos Comunes de Leucocito/inmunología , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/inmunología , Adolescente , Autoinmunidad/genética , Linfocitos T CD4-Positivos/metabolismo , Niño , Estudios de Cohortes , Síndrome de DiGeorge/genética , Femenino , Humanos , Antígenos Comunes de Leucocito/metabolismo , Masculino , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Timo/inmunología , Timo/metabolismo , Adulto JovenAsunto(s)
Linfocitos B/metabolismo , Síndromes de Inmunodeficiencia/diagnóstico , Tamizaje Neonatal/métodos , Biomarcadores/sangre , Pruebas con Sangre Seca , Humanos , Síndromes de Inmunodeficiencia/sangre , Síndromes de Inmunodeficiencia/inmunología , Recién Nacido , Masculino , Reacción en Cadena de la Polimerasa Multiplex , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
BACKGROUND: Chromosome 22q11.2 Deletion Syndrome (22q11.2DS) is the most frequent microdeletion syndrome and is mainly characterized by congenital cardiac defects, dysmorphic features, hypocalcemia, palatal dysfunction, developmental delay, and impaired immune function due to thymic hypoplasia or aplasia. Thyroid anomalies are frequently reported in patients with 22q11.2DS, although only a few well-structured longitudinal studies about autoimmune thyroid disease (ATD) have been reported. AIM: To longitudinally evaluate the frequency of thyroid anomalies and ATD in patients with 22q11.2DS. PATIENTS AND METHODS: Pediatric patients with a confirmed genetic diagnosis of 22q11.2DS were recruited and followed up on longitudinally. Clinical, biochemical, and immunological data were collected, as well as thyroid function, autoimmunity, and thyroid sonographic data. RESULTS: The study included 73 children with 22q11.2DS, with a mean follow-up duration of 9.51 ± 5.72 years. In all, 16 of the 73 enrolled patients (21.9%) developed ATD before 18 years of age (mean age 12.92 ± 3.66 years). A total of 20.5% developed Hashimoto's Thyroiditis (HT), of whom 50% required L-thyroxine treatment; 1.4% developed Graves Disease. Thyroid hypoplasia was found in 6/16 patients with ATD and left lobe hypoplasia in 9/16 patients. These features were also found in patients affected by 22q11.2DS without ATD. Among patients who developed ATD, at the first altered ultrasound scan, the most frequent anomalies suggestive of thyroiditis were inhomogeneous echotexture, diffuse or irregular hypo-echogenicity, and vascular overflow. CONCLUSION: We strongly recommend periodic screening of thyroid function and for autoimmunity in patients affected by 22q11.2DS. Along with blood tests, ultrasound scans of the thyroid gland should be performed periodically since some patients who go on to develop an ATD could have specific anomalies on ultrasound prior to any other anomaly.
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Síndrome de DiGeorge , Cardiopatías Congénitas , Adolescente , Niño , Estudios de Cohortes , Síndrome de DiGeorge/diagnóstico por imagen , Síndrome de DiGeorge/epidemiología , Síndrome de DiGeorge/genética , Cardiopatías Congénitas/genética , Humanos , Estudios Longitudinales , TiroxinaRESUMEN
Immune response to tuberculosis (TB) has been extensively studied in the past decades and classically involves cellular immunity. However, evidence suggests that humoral immunity may play a relevant role. Past studies regarding serum immunoglobulin (Ig) levels in TB are dated and only involve adult subjects. In this study, we retrospectively studied a cohort of 256 children with TB disease and analyzed 111 patients screened for total serum Ig at diagnosis. According to the severity and extent of organ involvement, subjects were divided into four groups, namely, uncomplicated pulmonary TB (UCPTB, 56.3% of patients), complicated pulmonary TB (CPTB, 22.5%), lymph node extrapulmonary TB (LN-EPTB, 7.2%), and extra-nodal extrapulmonary TB (EN-EPTB, 13.5%). Serum IgG and IgA levels were significantly higher in more severe and extended TB disease. Median IgG levels progressively increased from uncomplicated to complicated pulmonary and nodal forms, reaching their highest values in diffuse extra-pulmonary TB. In parallel, UCPTB showed significantly lower frequencies of patients presenting a substantial increase in IgG levels when compared with the other three groups. No relevant differences in IgM levels were detected. Ig screening at follow-up showed a significant reduction in IgG and IgA levels. Finally, we unveiled three cases of selective IgA and one case of selective IgM deficiencies (SIgMD), the latter with a severe clinical course. Serum IgG and IgA may be a useful clinical tool to assess the severity and monitor the treatment response in pediatric TB disease. Moreover, immunological workup in children with TB disease may unmask primary defects of humoral immunity.
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BACKGROUND: Classic infantile onset of Pompe disease (c-IOPD) leads to hypotonia and hypertrophic cardiomyopathy within the first days to weeks of life and, without treatment, patients die of cardiorespiratory failure in their first 1-2 years of life. Enzymatic replacement therapy (ERT) with alglucosidase alfa is the only available treatment, but adverse immune reactions can reduce ERT's effectiveness and safety. It is therefore very important to identify strategies to prevent and manage these complications. Several articles have been written on this disease over the last 10 years, but no univocal indications have been established. METHODS: Our study presents a review of the current literature on management of immune responses to ERT in c-IOPD as considered by an Italian study group of pediatric metabolists and immunologists in light of our shared patient experience. RESULTS: We summarize the protocols for the management of adverse reactions to ERT, analyzing their advantages and disadvantages, and provide expert recommendations for their optimal management, to the best of current knowledge. However, further studies are needed to improve actual management protocols, which still have several limitations.
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Enfermedad del Almacenamiento de Glucógeno Tipo II , Niño , Terapia de Reemplazo Enzimático , Enfermedad del Almacenamiento de Glucógeno Tipo II/terapia , Humanos , Inmunidad , Italia , alfa-Glucosidasas/efectos adversos , alfa-Glucosidasas/uso terapéuticoAsunto(s)
Infecciones por Citomegalovirus/inmunología , Infecciones por Virus de Epstein-Barr/inmunología , Linfohistiocitosis Hemofagocítica/inmunología , Receptores de Interferón/deficiencia , Tuberculosis/inmunología , Virosis/inmunología , Secuencia de Bases , Preescolar , Infecciones por Citomegalovirus/complicaciones , Infecciones por Citomegalovirus/microbiología , Infecciones por Citomegalovirus/virología , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/microbiología , Infecciones por Virus de Epstein-Barr/virología , Resultado Fatal , Femenino , Humanos , Lactante , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/patología , Linfohistiocitosis Hemofagocítica/complicaciones , Linfohistiocitosis Hemofagocítica/microbiología , Linfohistiocitosis Hemofagocítica/virología , Datos de Secuencia Molecular , Mutación , Neutrófilos/inmunología , Neutrófilos/patología , Receptores de Interferón/genética , Receptores de Interferón/inmunología , Linfocitos T Citotóxicos/inmunología , Linfocitos T Citotóxicos/patología , Tuberculosis/complicaciones , Tuberculosis/microbiología , Tuberculosis/virología , Virosis/complicaciones , Virosis/microbiología , Virosis/virologíaRESUMEN
BACKGROUND: Surveillance of serogroup B Neisseria meningitidis (MenB) subcapsular antigen variant distribution in invasive disease (IMD) is fundamental for multicomponent vaccine coverage prediction. IMD incidence in Tuscany in 2018 was 0.37/100,000 inhabitants, with MenB representing 57% of cases. More than 50% of MenB responsible for IMD cannot be grown in culture, and molecular characterization of these cases is often lacking. The aim of the present study was to describe the distribution of MenB subcapsular antigens, comparing their distribution in culture-positive and culture-negative cases. METHODS: Molecular data regarding clonal complexes and subcapsular antigen variants of the 55 MenB-IMD occurring in Tuscany from 2007 to 2019 were made available, and their distribution between culture-positive and culture-negative cases was compared. Genetic-MATS and MenDeVAR prediction systems were used to assess multicomponent vaccine coverage predictions. RESULTS: Culture-positive and culture-negative cases presented a similar percentage representation of fHbp subfamilies. Clonal complex 162 was almost constantly associated with fHbp B231/v1.390, Neisserial-heparin-binding-antigen (NHBA) peptide 20, and PorinA P1.22,14 (BAST-3033): these were the most represented antigenic variants, both in culture-positive and culture-negative groups. Point-estimate 4CMenB coverage prediction was 88.5% (84.6%-92.3%). CONCLUSIONS: Our data demonstrate that non-cultivable meningococci, responsible for IMD, possess genetic variants of subcapsular antigens that are representative of what has been observed in culture. The vaccine-related antigenic epidemiology of MenB is thus similar in both groups. One of the first on-field applications of gMATS and MenDeVAR identifies their major advantage in their accessibility and in the possibility of dynamic data implementation that must be pursued continuously in the future.