RESUMEN
Patients with ataxia-telangiectasia (A-T) suffer from progressive cerebellar ataxia, immunodeficiency, respiratory failure, and cancer susceptibility. From a clinical point of view, A-T patients with IgA deficiency show more symptoms and may have a poorer prognosis. In this study, we analyzed mortality and immunity data of 659 A-T patients with regard to IgA deficiency collected from the European Society for Immunodeficiencies (ESID) registry and from 66 patients with classical A-T who attended at the Frankfurt Goethe-University between 2012 and 2018. We studied peripheral B- and T-cell subsets and T-cell repertoire of the Frankfurt cohort and survival rates of all A-T patients in the ESID registry. Patients with A-T have significant alterations in their lymphocyte phenotypes. All subsets (CD3, CD4, CD8, CD19, CD4/CD45RA, and CD8/CD45RA) were significantly diminished compared to standard values. Patients with IgA deficiency (n = 35) had significantly lower lymphocyte counts compared to A-T patients without IgA deficiency (n = 31) due to a further decrease of naïve CD4 T-cells, central memory CD4 cells, and regulatory T-cells. Although both patient groups showed affected TCR-ß repertoires compared to controls, no differences could be detected between patients with and without IgA deficiency. Overall survival of patients with IgA deficiency was significantly diminished. For the first time, our data show that patients with IgA deficiency have significantly lower lymphocyte counts and subsets, which are accompanied with reduced survival, compared to A-T patients without IgA deficiency. IgA, a simple surrogate marker, is indicating the poorest prognosis for classical A-T patients. Both non-interventional clinical trials were registered at clinicaltrials.gov 2012 (Susceptibility to infections in ataxia-telangiectasia; NCT02345135) and 2017 (Susceptibility to Infections, tumor risk and liver disease in patients with ataxia-telangiectasia; NCT03357978).
Asunto(s)
Ataxia Telangiectasia/inmunología , Ataxia Telangiectasia/mortalidad , Linfocitos B/inmunología , Deficiencia de IgA/inmunología , Subgrupos de Linfocitos T/inmunología , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Deficiencia de IgA/mortalidad , Deficiencia de IgG/inmunología , Deficiencia de IgG/mortalidad , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Lactante , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: Factors associated with IgG levels in adults with IgG subclass deficiency (IgGSD) are incompletely understood. We studied adults with IgGSD with subnormal IgG1 only, subnormal IgG1/IgG3, or subnormal IgG3 only without other subnormal IgG subclasses, IgA, or IgM. We compiled: age; sex; autoimmune condition(s) (AC); atopy; IgG, IgG subclasses, IgA, IgM; IgGsum (IgG1 + IgG2 + IgG3 + IgG4); and D (percentage difference between IgGsum and IgG). We compared attributes of patients with/without subnormal IgG (< 7.00 g/L; subnormal IgG1 subclass groups only) and analyzed IgGsum and IgG relationships. We performed backward stepwise regressions on IgG using independent variables IgG subclasses, age, and sex and on D using independent variables age and sex. RESULTS: There were 39 patients with subnormal IgG1 only (89.7% women), 53 with subnormal IgG1/IgG3 (88.7% women), and 115 with subnormal IgG3 only (91.3% women). Fifteen patients (38.5%) and 32 patients (60.4%) in the respective subnormal IgG1 subclass groups had subnormal IgG. Attributes of patients with/without IgG < 7.00 g/L were similar, except that AC prevalence was lower in patients with subnormal IgG1 only and IgG < 7.00 g/L than ≥ 7.00 g/L (p = 0.0484). Mean/median IgG1 and IgG2 were significantly lower in patients with IgG < 7.00 g/L in both subnormal IgG1 subclass groups (p < 0.0001, all comparisons). Regressions on IgG in three subclass groups revealed positive associations with IgG1 and IgG2 (p < 0.0001 each association). Regressions on D revealed no significant association. IgG1 percentages of IgGsum were lower and IgG2 percentages were higher in patients with subnormal IgG1 subclass levels than subnormal IgG3 only (p < 0.0001 all comparisons). CONCLUSIONS: We conclude that both IgG1 and IgG2 are major determinants of IgG in patients with subnormal IgG1, combined subnormal IgG1/IgG3, or subnormal IgG3 and that in patients with subnormal IgG1 or combined subnormal IgG1/IgG3, median IgG2 levels are significantly lower in those with IgG < 7.00 g/L than those with IgG ≥ 7.00 g/L.
Asunto(s)
Enfermedades Autoinmunes/inmunología , Deficiencia de IgG/inmunología , Inmunoglobulina G/genética , Isotipos de Inmunoglobulinas/genética , Adulto , Anciano , Enfermedades Autoinmunes/epidemiología , Femenino , Humanos , Deficiencia de IgG/epidemiología , Masculino , Persona de Mediana Edad , Estudios Seroepidemiológicos , Estados Unidos/epidemiologíaRESUMEN
Background: Patients with primary humoral immunodeficiency are more prone to invasive as well as recurrent pneumococcal infections. Therefore, anti-pneumococcal vaccination including the 13-valent conjugate vaccine is recommended. Nevertheless, to date, no data is available on immunogenicity of this vaccine in this population. Objective: To assess the immunogenicity and the persistence of protection up to one year after a 13-valent pneumococcal conjugate vaccine in patients with primary humoral immunodeficiency. Methods: Twenty-nine patients with common variable immunodeficiency or IgG subclass deficiency were vaccinated. Immune response and immune protection at baseline as well as at one, six and twelve months after vaccination were evaluated by measuring specific IgG serum concentrations (ELISA), and opsonophagocytic activities directed against selected pneumococcal (MOPA). Results: By ELISA, half of the patients had protective IgG concentrations before vaccination, 35.7% showed an immune response one month after vaccination, 71.4%, 66.7% and 56.0% of the patients were protected at one, six and twelve months respectively. Conversely, by MOPA, 3.4% of the patients were protected at baseline, 10.7% showed an immune response and 28.6%, 48.2% and 33.3% were protected at one, six and twelve months respectively. IgG subclass deficiency, Ig replacement therapy and higher IgG2 concentrations at diagnosis were associated with long-term protection. Conclusion: Pneumococcal conjugate vaccine improves immune protection and antibodies' functionality in a subset of patients with primary immunodeficiency. Prime-boost vaccine strategy needs to be better and individually adapted.
Asunto(s)
Inmunodeficiencia Variable Común/inmunología , Inmunodeficiencia Variable Común/terapia , Deficiencia de IgG/inmunología , Deficiencia de IgG/terapia , Vacunas Neumococicas/uso terapéutico , Adulto , Anciano , Anticuerpos Antibacterianos/sangre , Especificidad de Anticuerpos , Femenino , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/clasificación , Masculino , Persona de Mediana Edad , Fagocitosis/inmunología , Infecciones Neumocócicas/inmunología , Infecciones Neumocócicas/prevención & control , Serogrupo , Streptococcus pneumoniae/clasificación , Streptococcus pneumoniae/inmunología , Factores de Tiempo , Vacunas Conjugadas/uso terapéutico , Adulto JovenAsunto(s)
Deficiencia de IgG/inmunología , Inmunoglobulina G/inmunología , Enfermedad Pulmonar Obstructiva Crónica/inmunología , Infecciones del Sistema Respiratorio/inmunología , Agammaglobulinemia/epidemiología , Agammaglobulinemia/inmunología , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Femenino , Humanos , Deficiencia de IgG/epidemiología , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Enfermedad Pulmonar Obstructiva Crónica/mortalidad , Infecciones del Sistema Respiratorio/epidemiologíaRESUMEN
Purpose: Individuals with immunoglobulin G deficiency (IgGsd) often complain of fatigue. The correlation between systemic inflammation and fatigue is unknown. In this study perceived quality of life (QoL) and fatigue in individuals with IgGsd, on and off immunoglobulin replacement therapy (IgRT) were correlated to inflammatory markers in plasma to identify the subgroup that benefits from IgRT. Method: Thirty-five IgGsd-patients were sampled on three occasions: at baseline, after being on IgRT for at least 18 months, and 18 months after discontinuation of IgRT. Short form 36, EQ-5D-5L visual analogue scale and fatigue impact scale questionnaires were used for evaluation of QoL and fatigue. Furthermore, a panel of 92 inflammatory markers were analysed in plasma. Thirty-two gender- and age-matched healthy individuals were included as controls and sampled on one occasion. Results: QoL was lower and perceived fatigue higher in IgGsd compared to the controls. Severe fatigue and low QoL were associated with the need to restart IgRT (which is considered in IgGsd-individuals with a high burden of infections in Sweden). Twenty-five inflammatory factors were dysregulated in IgGsd and the plasma protein patterns were similar regardless of whether IgRT was ongoing or not. Enrichment analysis indicated IL-10 signalling as the most affected pathway. Severe fatigue was associated with decreased levels of the neurotrophic factors VEGFA and CSF-1. Conclusion: Fatigue is a major contributory factor to impaired health-related QoL in IgGsd and is related to the need for IgRT. Low-grade systemic inflammation is a potential driver of fatigue. In addition to the burden of infections, we suggest the degree of fatigue should be considered when the decision to introduce IgRT is made.
Asunto(s)
Fatiga/tratamiento farmacológico , Fatiga/inmunología , Deficiencia de IgG/inmunología , Inmunoglobulina G/uso terapéutico , Inflamación/inmunología , Encuestas y Cuestionarios , Adulto , Anciano , Quimiocina CXCL1/inmunología , Quimiocina CXCL1/metabolismo , Quimiocina CXCL5/inmunología , Quimiocina CXCL5/metabolismo , Fatiga/complicaciones , Femenino , Humanos , Deficiencia de IgG/complicaciones , Inmunoglobulina G/inmunología , Inflamación/complicaciones , Péptidos y Proteínas de Señalización Intercelular/inmunología , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Interleucina-10/inmunología , Interleucina-10/metabolismo , Masculino , Persona de Mediana Edad , Calidad de Vida , Suecia , Adulto JovenAsunto(s)
Asma/inmunología , COVID-19/inmunología , Inmunodeficiencia Variable Común/inmunología , Deficiencia de IgG/inmunología , Obesidad Mórbida/inmunología , Infecciones Estafilocócicas/inmunología , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/uso terapéutico , Adulto , Alanina/análogos & derivados , Alanina/uso terapéutico , Antivirales/uso terapéutico , Asma/patología , Asma/terapia , Asma/virología , COVID-19/patología , COVID-19/terapia , COVID-19/virología , Inmunodeficiencia Variable Común/patología , Inmunodeficiencia Variable Común/terapia , Inmunodeficiencia Variable Común/virología , Resultado Fatal , Humanos , Deficiencia de IgG/patología , Deficiencia de IgG/terapia , Deficiencia de IgG/virología , Inmunización Pasiva , Inmunoglobulina G/sangre , Inmunoglobulinas Intravenosas/uso terapéutico , Masculino , Staphylococcus aureus Resistente a Meticilina , Obesidad Mórbida/patología , Obesidad Mórbida/terapia , Obesidad Mórbida/virología , SARS-CoV-2 , Infecciones Estafilocócicas/patología , Infecciones Estafilocócicas/terapia , Infecciones Estafilocócicas/virología , Sueroterapia para COVID-19RESUMEN
BACKGROUND: Patients with an IgG subclass deficiency (IgSD) ± specific polysaccharide antibody deficiency (SPAD) often present with recurrent infections. Previous retrospective studies have shown that prophylactic antibiotics (PA) and immunoglobulin replacement therapy (IRT) can both be effective in preventing these infections; however, this has not been confirmed in a prospective study. OBJECTIVE: To compare the efficacy of PA and IRT in a randomized crossover trial. METHODS: A total of 64 patients (55 adults and 9 children) were randomized (2:2) between two treatment arms. Treatment arm A began with 12 months of PA, and treatment arm B began with 12 months of IRT. After a 3-month bridging period with cotrimoxazole, the treatment was switched to 12 months of IRT and PA, respectively. The efficacy (measured by the incidence of infections) and proportion of related adverse events in the two arms were compared. RESULTS: The overall efficacy of the two regimens did not differ (p = 0.58, two-sided Wilcoxon signed-rank test). A smaller proportion of patients suffered a related adverse event while using PA (26.8% vs. 60.3%, p < 0.0003, chi-squared test). Patients with persistent infections while using PA suffered fewer infections per year after switching to IRT (2.63 vs. 0.64, p < 0.01). CONCLUSION: We found comparable efficacy of IRT and PA in patients with IgSD ± SPAD. Patients with persistent infections during treatment with PA had less infections after switching to IRT. CLINICAL IMPLICATION: Given the costs and associated side-effects of IRT, it should be reserved for patients with persistent infections despite treatment with PA.
Asunto(s)
Profilaxis Antibiótica/métodos , Inmunoglobulina G/inmunología , Síndromes de Inmunodeficiencia/inmunología , Enfermedades de Inmunodeficiencia Primaria/inmunología , Enfermedades de Inmunodeficiencia Primaria/terapia , Niño , Femenino , Humanos , Deficiencia de IgG/inmunología , Masculino , Persona de Mediana Edad , Infección Persistente/inmunologíaRESUMEN
The number of people suffering from the new coronavirus SARS-CoV-2 continues to rise. In SARS-CoV-2, superinfection with bacteria or fungi seems to be associated with increased mortality. The role of co-infections with respiratory viral pathogens has not yet been clarified. Here, we report the course of COVID-19 in a CLL patient with secondary immunodeficiency and viral co-infection with parainfluenza.
Asunto(s)
COVID-19/complicaciones , Coinfección/complicaciones , Leucemia Linfocítica Crónica de Células B/complicaciones , Infecciones por Paramyxoviridae/complicaciones , Anticuerpos Antivirales/sangre , COVID-19/inmunología , COVID-19/terapia , Humanos , Deficiencia de IgG/complicaciones , Deficiencia de IgG/inmunología , Deficiencia de IgG/terapia , Inmunoglobulinas Intravenosas/uso terapéutico , Leucemia Linfocítica Crónica de Células B/inmunología , Leucemia Linfocítica Crónica de Células B/terapia , Masculino , Persona de Mediana Edad , Pandemias , SARS-CoV-2/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunologíaRESUMEN
The purpose of this study is to describe both clinical and immunological features in large cohort of adult patients with IgG subclass deficiency, and response to immunoglobulin therapy. This is a retrospective study of data obtained from electronic medical records and paper charts of 78 patients with IgG subclass deficiency seen and followed at our immunology clinics from 2010 to 2016. Both isolated selective IgG subclass deficiency as well as combined (two) subclass deficiencies were observed. IgG3 subclass deficiency, isolated and in combination with other IgG subclass deficiency, is the most frequent of IgG subclass deficiency. A majority of patients presented with upper and lower respiratory tract infections, especially chronic sinusitis. Both allergic and autoimmune manifestations are common; however, there is no subclass preference. The proportions and absolute numbers of CD3+ T cells, CD4+ T and CD8+ T cells, CD19+ B cells, and CD3-CD16+CD56+ NK cells were normal in the majority of patients in all IgG subclass deficiencies. Total serum IgG levels did not correlate with IgG subclass levels across all IgG subclass deficiencies. Anti-pneumococcal polysaccharide antibody responses were impaired in 56% of patients. IgG3 subclass deficiency is the most common IgG subclass deficiency, and anti-polysaccharide antibody responses are distributed among IgG subclasses with modest preference in IgG2 subclass. The majority of patients treated with immunoglobulin responded by reduction in frequency of infections and requirement of antibiotics.
Asunto(s)
Deficiencia de IgG/inmunología , Deficiencia de IgG/patología , Adulto , Anciano , Femenino , Humanos , Deficiencia de IgG/sangre , Deficiencia de IgG/tratamiento farmacológico , Inmunoglobulina G/administración & dosificación , Inmunoglobulina G/sangre , Subgrupos Linfocitarios/inmunología , Subgrupos Linfocitarios/patología , Masculino , Persona de Mediana Edad , Vacunas Neumococicas/inmunología , Infecciones del Sistema Respiratorio/sangre , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/inmunología , Infecciones del Sistema Respiratorio/patología , Estudios Retrospectivos , Sinusitis/sangre , Sinusitis/tratamiento farmacológico , Sinusitis/inmunología , Sinusitis/patología , Resultado del Tratamiento , Adulto JovenAsunto(s)
Deficiencia de IgG , Anticuerpos Antibacterianos/inmunología , Humanos , Deficiencia de IgG/diagnóstico , Deficiencia de IgG/tratamiento farmacológico , Deficiencia de IgG/inmunología , Inmunoglobulina G/inmunología , Inmunoglobulina G/uso terapéutico , Vacunas Neumococicas , Polisacáridos Bacterianos/inmunología , Streptococcus pneumoniae/inmunologíaRESUMEN
Many adults with IgG subclass deficiency (IgGSD) experience long intervals of frequent/severe respiratory tract infection before IgGSD diagnosis, but reasons for delays in IgGSD diagnoses are incompletely understood. We performed a retrospective study of 300 white adults (ages ≥18 y) with IgGSD including frequency analyses of age at IgGSD diagnosis, duration of frequent/severe respiratory tract infection before IgGSD diagnosis, and age at onset of frequent/severe infection (calculated). We performed multivariable regressions on age at diagnosis, infection duration, and age at infection onset using these variables, as appropriate: sex; age at diagnosis; diabetes; autoimmune condition(s); atopy; allergy; corticosteroid use; body mass index; serum immunoglobulin isotype levels; blood lymphocyte subsets; three IgGSD-associated human leukocyte antigen-A and -B haplotypes; and referring physician specialties. Mean age at diagnosis was 50 ± 12 (standard deviation) y (median 50 y (range 19-79)). There were 247 women (82.3%). Mean infection duration at IgGSD diagnosis was 12 ± 13 y (median 7 y (range 1-66)). Mean age at infection onset was 38 ± 16 y (median 38 y (range 4, 76)). Age at infection onset was ≥18 y in 95.7% of subjects. Regressions on age at diagnosis and infection duration revealed no significant associations. Regression on age at infection onset revealed one positive association: age at diagnosis (p <0.0001). We conclude that the median duration of frequent/severe respiratory tract infection in adults before IgGSD diagnosis was 7 y. Older adults may be diagnosed to have IgGSD after longer intervals of infection than younger adults. Duration of frequent/severe respiratory tract infection before IgGSD diagnosis was not significantly associated with routine clinical and laboratory variables, including referring physician specialties.
Asunto(s)
Diagnóstico Tardío/estadística & datos numéricos , Deficiencia de IgG/diagnóstico , Isotipos de Inmunoglobulinas/clasificación , Infecciones del Sistema Respiratorio/diagnóstico , Adulto , Factores de Edad , Edad de Inicio , Anciano , Índice de Masa Corporal , Femenino , Expresión Génica , Antígenos HLA-A/clasificación , Antígenos HLA-A/genética , Antígenos HLA-A/inmunología , Antígenos HLA-B/clasificación , Antígenos HLA-B/genética , Antígenos HLA-B/inmunología , Haplotipos , Humanos , Deficiencia de IgG/sangre , Deficiencia de IgG/inmunología , Deficiencia de IgG/fisiopatología , Isotipos de Inmunoglobulinas/sangre , Subgrupos Linfocitarios/clasificación , Masculino , Persona de Mediana Edad , Infecciones del Sistema Respiratorio/sangre , Infecciones del Sistema Respiratorio/inmunología , Infecciones del Sistema Respiratorio/fisiopatología , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Factores Sexuales , Factores de TiempoRESUMEN
BACKGROUND: Common variable immunodeficiency (CVID) and IgG deficiency are 2 of the more prevalent primary humoral immune defects. The former is defined by consensus with criteria for quantitative and qualitative antibody defects, whereas the latter is used to describe patients with reduced IgG, who commonly have recurrent sinopulmonary infections but do not fulfill CVID criteria. However, these patients are often given this diagnosis. OBJECTIVE: To compare immunologic findings and clinical manifestations of 2 large cohorts of patients with CVID or IgG deficiency to better delineate differences between these syndromes. METHODS: We extracted clinical and laboratory data from electronic medical records of patients at our institution who had received International Classification of Disease codes for either CVID, or IgG deficiency. We gathered immunoglobulin levels, lymphocyte subpopulation counts, and serological vaccine responses. In some patients, we performed flow cytometry to determine percentages of memory and switched-memory B cells. We compiled and statistically compared clinical data related to infectious manifestations, bronchiectasis, autoimmune diseases, infiltrative inflammatory processes, and lymphoid malignancies. RESULTS: In contrast to IgG-deficient patients, we found that patients with CVID had lower IgG levels, greater unresponsiveness to most vaccines, lower percentages of memory and isotype switched-memory B cells, and lower CD4 T-cell counts. Clinically, patients with CVID presented similar rates of sinusitis and pneumonias, but a significantly higher prevalence of bronchiectasis and especially noninfectious complications. CONCLUSIONS: CVID and IgG deficiency do not share the same disease spectrum, the former being associated with immunodysregulative manifestations and markers of a more severe immune defect. These data may allow clinicians to distinguish these conditions and the management differences that these patients pose.
Asunto(s)
Linfocitos B/inmunología , Inmunodeficiencia Variable Común/inmunología , Deficiencia de IgG/inmunología , Memoria Inmunológica/inmunología , Linfocitos T/inmunología , Enfermedades Autoinmunes/epidemiología , Subgrupos de Linfocitos B/inmunología , Bronquiectasia/epidemiología , Estudios de Cohortes , Inmunodeficiencia Variable Común/epidemiología , Femenino , Citometría de Flujo , Humanos , Deficiencia de IgG/epidemiología , Inmunoglobulina A/inmunología , Inmunoglobulina G/inmunología , Inmunoglobulina M/inmunología , Inmunofenotipificación , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Neumonía/epidemiología , Pruebas Serológicas , Sinusitis/epidemiología , Vacunas/inmunologíaRESUMEN
Respiratory tract infections in children are one of the most common causes for medical consultations. When the infections are of recurring nature, they are a major reason for the diagnostics for primary immunodeficiency that is in about 65% of cases underlain by disorders of humoral immunity. This study seeks to retrospectively evaluate the history of recurrent respiratory tract infections in children with humoral disorders and the associations among deficiencies in the immune system components. We evaluated 394 children aged 3 months to 18 years. We found 49.5% (195 cases) of children with IgG deficiencies, all of whom had normal IgE levels. There were 8.4% (33 cases) of IgA deficiency, 7.4% (29 cases) of IgM insufficiency, and 4.1% (16 cases) of CD19+ cells deficiency. The elevated level of CD19+ cells was found in 27.7% (109 out of the 394 children). Immunoglobulin deficiencies often coexisted with a deficiency in another immunoglobulin class above outlined. There was an interdependence between IgA abnormality and IgG, IgG3, and IgG4 abnormalities as well as between IgM abnormality and IgG and IgG1 abnormalities. We conclude that respiratory tract infections in children are often underlain by a convergence of IgG with both IgA and IgM abnormal states. The physiopathological meaning of this convergence for the infection course and resulting functional respiratory changes remains elusive.
Asunto(s)
Deficiencia de IgG/complicaciones , Inmunidad Humoral , Infecciones del Sistema Respiratorio/complicaciones , Adolescente , Niño , Preescolar , Humanos , Deficiencia de IgG/inmunología , Inmunoglobulina G , Lactante , Recurrencia , Infecciones del Sistema Respiratorio/inmunología , Estudios RetrospectivosRESUMEN
BACKGROUND: Deficits in disorders of humoral immunity associated with a deficit of antibodies are the most common primary immunodeficiency. Total IgG and IgG subclasses measurements are used to diagnose, differentiate and control in patients with primary and secondary immunodeficiencies. METHODS: The purpose of the study was to analyze the structure patients group according to difference between total IgG and sum of the IgG subclasses and to determine factors affecting the level of this difference. This study was based on data collected from 670 children referred to the Department of Clinical Immunology and Pediatrics in order to diagnose the immune disorders. For all children the level of the total of immunoglobulins IgG and of the IgG subclasses (IgG1, IgG2, IgG3, IgG4) were determined. The group of children was divided into subgroups according to gender, age (under 6 years of age, 6.5-12 years, and 12-18 years), and IgG abnormality (below the normal range, normal and above the normal range). In the patients group, the total IgG values were on average higher than sum of the IgG subclasses. RESULTS: Statistical analysis shown the all parameters under study (age, gender and IgG abnormality) influence statistically significant on the discrepancy between the sum of the IgG subclasses and total IgG. Assessment of IgG and IgG subclasses levels is based on different methods what causes the discrepancy between the sum of the IgG subclasses and total IgG. CONCLUSIONS: Standardization in that regard is crucial. In addition, we have shown the reliability of the results obtained. Despite the determination in two different laboratories and on different analyzers, as well as the freezing process does not affect the test results.
Asunto(s)
Inmunoglobulina G/sangre , Inmunoglobulina G/clasificación , Síndromes de Inmunodeficiencia/inmunología , Adolescente , Niño , Preescolar , Femenino , Humanos , Deficiencia de IgG/inmunología , Inmunidad Humoral/inmunología , Lactante , Masculino , Reproducibilidad de los ResultadosAsunto(s)
Glositis Migratoria Benigna/genética , Glositis Migratoria Benigna/inmunología , Heterocigoto , Deficiencia de IgG/genética , Interleucinas/genética , Mutación , Psoriasis/genética , Psoriasis/inmunología , Biomarcadores/sangre , Biopsia , Análisis Mutacional de ADN , Predisposición Genética a la Enfermedad , Glositis Migratoria Benigna/sangre , Glositis Migratoria Benigna/diagnóstico , Humanos , Deficiencia de IgG/sangre , Deficiencia de IgG/diagnóstico , Deficiencia de IgG/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Masculino , Fenotipo , Psoriasis/sangre , Psoriasis/diagnóstico , Piel/inmunología , Piel/patología , Adulto JovenRESUMEN
Immune dysfunction attributed to hypogammaglobulinaemia is common in chronic lymphocytic leukaemia (CLL) and infection is a major contributor to morbidity and mortality. A higher incidence of multiple immunoglobulin and immunoglobulin G (IgG) subclass deficiency was associated with more advanced disease (P < 0·001 and P < 0·001, respectively) in a cohort of 147 CLL patients. Multiple immunoglobulin and IgG subclass deficiency were significantly associated with shorter treatment-free survival (TFS) (P < 0·001 and P = 0·006, respectively). The association between disease stage and immune dysfunction demonstrated by these data suggest aspects of immune deficiency correlate with disease severity and may be associated with shorter TFS in CLL.
Asunto(s)
Deficiencia de IgG , Inmunidad Humoral , Leucemia Linfocítica Crónica de Células B , Anciano , Supervivencia sin Enfermedad , Femenino , Humanos , Deficiencia de IgG/sangre , Deficiencia de IgG/inmunología , Deficiencia de IgG/mortalidad , Deficiencia de IgG/terapia , Leucemia Linfocítica Crónica de Células B/sangre , Leucemia Linfocítica Crónica de Células B/inmunología , Leucemia Linfocítica Crónica de Células B/mortalidad , Leucemia Linfocítica Crónica de Células B/terapia , Masculino , Persona de Mediana Edad , Tasa de SupervivenciaRESUMEN
In mice, the IgG subclass induced after Ag encounter can reflect the nature of the Ag. Th2 Ags such as alum-precipitated proteins and helminths induce IgG1, whereas Th1 Ags, such as Salmonella Typhimurium, predominantly induce IgG2a. The contribution of different IgG isotypes to protection against bacteria such as S. Typhimurium is unclear, although as IgG2a is induced by natural infection, it is assumed this isotype is important. Previously, we have shown that purified S. Typhimurium porins including outer membrane protein OmpD, which induce both IgG1 and IgG2a in mice, provide protection to S. Typhimurium infection via Ab. In this study we report the unexpected finding that mice lacking IgG1, but not IgG2a, are substantially less protected after porin immunization than wild-type controls. IgG1-deficient mice produce more porin-specific IgG2a, resulting in total IgG levels that are similar to wild-type mice. The decreased protection in IgG1-deficient mice correlates with less efficient bacterial opsonization and uptake by macrophages, and this reflects the low binding of outer membrane protein OmpD-specific IgG2a to the bacterial surface. Thus, the Th2-associated isotype IgG1 can play a role in protection against Th1-associated organisms such as S. Typhimurium. Therefore, individual IgG subclasses to a single Ag can provide different levels of protection and the IgG isotype induced may need to be a consideration when designing vaccines and immunization strategies.
Asunto(s)
Anticuerpos Antibacterianos/inmunología , Inmunoglobulina G/inmunología , Porinas/inmunología , Vacunas contra la Salmonella/inmunología , Salmonella typhimurium/inmunología , Animales , Reacciones Antígeno-Anticuerpo , Adhesión Bacteriana/inmunología , Proteínas Bacterianas/inmunología , Línea Celular , Femenino , Deficiencia de IgG/inmunología , Inmunización , Cambio de Clase de Inmunoglobulina , Isotipos de Inmunoglobulinas/inmunología , Masculino , Ratones Endogámicos C57BL , Fagocitosis/inmunología , Salmonelosis Animal/prevención & controlAsunto(s)
Agammaglobulinemia/diagnóstico , Enfermedades Autoinmunes/diagnóstico , Bronquitis/diagnóstico , Deficiencia de IgG/diagnóstico , Infecciones del Sistema Respiratorio/diagnóstico , Adulto , Agammaglobulinemia/complicaciones , Agammaglobulinemia/inmunología , Agammaglobulinemia/patología , Enfermedades Autoinmunes/sangre , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/patología , Bronquitis/sangre , Bronquitis/inmunología , Bronquitis/patología , Femenino , Humanos , Deficiencia de IgG/complicaciones , Deficiencia de IgG/inmunología , Deficiencia de IgG/patología , Inmunoglobulina E/sangre , Inmunoglobulina G/sangre , Masculino , Persona de Mediana Edad , Infecciones del Sistema Respiratorio/complicaciones , Infecciones del Sistema Respiratorio/inmunología , Infecciones del Sistema Respiratorio/patología , Estudios RetrospectivosRESUMEN
The chance to analyse the four IgG subclasses arose with the publication of Terry and Fahey1 . Since then, a lot of new information on the role of subclasses and their deficiency states in humans has been obtained. This review tries to analyse critically our current knowledge of subclass deficiencies in children.
Asunto(s)
Deficiencia de IgG/diagnóstico , Niño , Humanos , Deficiencia de IgG/clasificación , Deficiencia de IgG/tratamiento farmacológico , Deficiencia de IgG/inmunología , Inmunoglobulina G/uso terapéutico , Factores Inmunológicos/uso terapéuticoRESUMEN
IgG2 is the most efficient subclass for providing protection against pneumococcal pathogens. We hypothesised that some individuals may be unable to mount an effective pneumococcal capsular polysaccharide (PCP) IgG2 response despite having a normal PCP IgG concentration (PCP IgG2 deficient). The median pre-vaccination PCP IgG2 concentration was significantly lower in individuals referred for immunological investigation compared to healthy controls (2.8 mg/L range, 95% CI 1.1-88 vs. 29.5mg/L, 95% CI 13.5-90, p = 0.0002). PCP IgG:IgG2 ratios were significantly higher for the referral population than for healthy controls suggesting the increased production of PCP specific subclasses other than IgG2. The percentage of individuals with PCP IgG2 deficiency was significantly higher in referral groups compared to controls (31% vs. 5%; p = 0.0009) and in an individual with PCP IgG2 deficiency, the balance of PCP specific IgG subclass antibodies post vaccination changed from IgG2>IgG1>IgG3>IgG4 to IgG1>IgG3>IgG2>IgG4. The median PCP IgG2 concentration in those with PCP IgG2 deficiency was significantly lower in the referral groups compared to controls (7.8 mg/L, 95% CI 1.1-12 vs. 12.7 mg/L, 95% CI 11.8-13.1; p = 0.006). The data suggests a defect in the production PCP IgG2 may be present in individuals with normal PCP IgG referred for immunological investigation.