RESUMO
Background: Immunoglobulin G (IgG) subclass deficiencies and isolated IgA, IgM, IgE deficiencies have all been described in the literature with variable prevalence. Methods: These isotype deficiencies have a variable presentation from asymptomatic to recurrent infections resistant to prophylactic antibiotics. Results: Atopic disorders and autoimmune diseases are common comorbidities. IgE deficiency has been associated with impaired vaccine response and an increased risk of malignancy, particularly in patients with no allergic comorbidities and those with non-common variable immunodeficiency (CVID) humoral immunodeficiency, IgM deficiency, IgG2 deficiency, and CD4 lymphopenia. Conclusion: Close monitoring for malignancy should be strongly considered for these patients who are at risk. Treatment is variable and may include antimicrobial therapies for illnesses and prophylactic antibiotics in select patients, and immunoglobulin replacement can be considered for patients with refractory, recurrent infections.
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Imunoglobulina E , Imunoglobulina M , Humanos , Imunoglobulina E/imunologia , Imunoglobulina M/imunologia , Imunoglobulina M/sangue , Imunoglobulina A/imunologia , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/imunologia , Imunoglobulina G/imunologia , Imunoglobulina G/sangue , Deficiência de IgA/imunologia , Deficiência de IgA/diagnóstico , Deficiência de IgG/diagnóstico , Deficiência de IgG/imunologiaRESUMO
Background: Immunoglobulin G subclass deficiencies (IgGsd) comprise a wide clinical spectrum from no symptoms to repeated respiratory infections and risk for the development of lung damage. Our aims were to investigate whether the immunological phenotype of IgGsd patients on and off immunoglobulin replacement therapy (IgRT) was reflected in the clinical features of IgGsd. Method: Thirty patients with IgGsd were included in this prospective study of 18 months of IgRT, followed by 7-18 months of IgRT discontinuation. Blood samples were collected when patients were on and off IgRT and compared with samples from 34 cross-sectional healthy controls. An in-depth lymphocyte phenotyping was performed by flow cytometry and plasma levels of immune checkpoints were assessed. Results: IgG3 subclass deficiency was most common. Patients with IgGsd had decreased levels of activated T cells and B cells and plasma levels of negative immune checkpoint molecules correlated negatively with T cell and B cell activation. The decreased T cell activation level was unaffected by IgRT, while the B cell activation was partly restored. Of note, decreased levels of activated regulatory T cells (Tregs) were found in IgGsd patients and was partly restored during IgRT. The profile of comorbidities did not associate with Treg levels. Discussion: IgGsd is associated with decreased B cell and T cell activation including Tregs, and increased plasma levels of negative immune checkpoint molecules. The consequence of reduced activated Tregs in IgGsd remains unclear. Decreased immune cell activation was partly restored during IgRT, demonstrating that IgRT may contribute to improved immune function in patients with IgGsd.
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Deficiência de IgG , Imunoglobulina G , Ativação Linfocitária , Linfócitos T Reguladores , Humanos , Masculino , Feminino , Linfócitos T Reguladores/imunologia , Pessoa de Meia-Idade , Adulto , Deficiência de IgG/imunologia , Ativação Linfocitária/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Estudos Transversais , Estudos Prospectivos , Idoso , Linfócitos B/imunologia , Proteínas de Checkpoint Imunológico/genética , Proteínas de Checkpoint Imunológico/metabolismo , Imunofenotipagem , Imunoglobulinas Intravenosas/uso terapêuticoRESUMO
Introduction: Primary antibody deficiencies (PAD) are inborn defects of the immune system that result in increased susceptibility to infections. Despite the reduced response to vaccination, PAD patients still benefit from it by reducing the risk of severe infections and complications. SARS-CoV-2 vaccines are recommended in PAD patients, but their immune effects are poorly studied. Here, we analyze virus-specific T-cell responses in PAD patients after booster vaccination against SARS-CoV-2. Patients and methods: The study included 57 adult PAD patients on long-term immunoglobulin replacement therapy (IgRT) diagnosed with X-linked agammaglobulinemia (XLA; n = 4), common variable immunodeficiency (CVID; n = 33), isotype defects or IgG subclass deficiency (n = 6), and unclassified IgG deficiency (n = 14). Of those, 49 patients (86%) received vaccination against SARS-CoV-2 using mRNA vaccine (Pfizer-BioNTech). T-cell responses were assessed at a median of 21 (13 - 30) weeks after the booster dose (mainly the third dose) using commercially available interferon-gamma release assay (IGRA) with recombinant SARS-CoV-2 spike S1 protein. Results: Vaccinated PAD patients showed an increased (3.8-fold, p = 0.004) release of IFN-γ upon S1 stimulation. In this group, we also documented higher serum levels of anti-SARS-CoV-2 IgG (4.1-fold, p = 0.01), although they were not associated with IGRA results. Further subgroup analysis revealed very similar IGRA responses in CVID and unclassified IgG deficiencies that were 2.4-fold increased compared to XLA and 5.4-fold increased compared to patients with isotype defects or IgG subclass deficiencies (e.g., vs. CVID: p = 0.016). As expected, CVID and XLA patients showed decreased serum titers of anti-SARS-CoV-2 antibodies compared to other studied groups (e.g., CVID vs. unclassified IgG deficiency: 4.4-fold, p = 0.006). The results did not depend directly on IgRT mode or dose, number of vaccine doses and time from the last booster dose, and clinical manifestations of PAD. Interestingly, anti-SARS-CoV-2 titers were positively correlated with serum immunoglobulin levels before IgRT (e.g., for IgA: r = 0.45, p<0.001; for IgG: r = 0.34, p = 0.009) and the percentage of peripheral blood NK cells (r = 0.48, p<0.001). Conclusions: Our results documented satisfactory in vitro cellular immune response in PAD patients after booster SARS-CoV-2 vaccination. Therefore, even patients with agammaglobulinemia should benefit from vaccination due to the apparent induction of cell-mediated immunity, which, together with IgRT, grants comprehensive protection against the pathogen.
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COVID-19 , Imunodeficiência de Variável Comum , Deficiência de IgG , Doenças da Imunodeficiência Primária , Adulto , Humanos , Vacinas contra COVID-19 , SARS-CoV-2 , Imunidade Celular , Imunodeficiência de Variável Comum/terapia , Anticorpos Antivirais , Imunoglobulina GRESUMO
Haemophilus influenzae can be divided into typeable and non-typeable strains. Although non-typeable Haemophilus influenzae (NTHi) is less likely to be a fatal bacterium, invasive NTHi infection has been reported to increase worldwide. This study presents a case of sudden death of a child with invasive NTHi infection and underlying immunoglobulin G2 (IgG2) deficiency. A two years seven months male child with a high fever was found unresponsive in bed, lying face down on a soft pillow. Later, the hospital declared the subject dead. An autopsy revealed that the only noteworthy finding was tissue congestion. The histopathological findings disclosed neutrophils within blood vessels of major organs. Meanwhile, the formation of the micro abscess was not visible, which indicated bacteremia. The bacterial blood culture was positive for Haemophilus Influenzae. Polymerase chain reaction assay revealed the absence of an entire capsule locus. The transmission electron microscopy showed that the colonies did not have polysaccharide capsules. Based on the above findings, the strain was identified as NTHi. Furthermore, the value of serum IgG2 was deficient, indicating the presence of IgG2 subclass deficiency. The subject eventually died from asphyxia by smothering due to a comorbid condition with a high fever brought on by NTHi-induced bacteremia and lying face down. IgG2 subclass deficiency contributed to the development of invasive NTHi infection. The invasive NTHi infection might present a risk of sudden death, particularly for immunocompromised children. As forensic pathologists and pediatricians may encounter such a problematic clinical condition, they should be aware of this.
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Infecções por Haemophilus , Haemophilus influenzae , Deficiência de IgG , Pré-Escolar , Humanos , Masculino , Morte Súbita/etiologia , Infecções por Haemophilus/diagnóstico , Haemophilus influenzae/isolamento & purificação , Deficiência de IgG/sangue , Deficiência de IgG/diagnósticoRESUMO
BACKGROUND: IgG subclass deficiency is a laboratory diagnosis and becomes important with recurrent infections. This study aimed to examine the demographic, clinical, and laboratory results of pediatric cases with IgG subclass deficiency and to improve the understanding of the clinical significance of IgG subclass deficiency. METHODS: In this study, the clinical and laboratory features of 111 pediatric patients, with at least one whose serum IgG subclasses was measured as lower than 2 standard deviation of healthy aged-matched control values, were evaluated. The clinical and laboratory features of the cases with isolated IgG subclass deficiency (Group 1) and those with low serum levels of any of IgG, IgA, and IgM in addition to the IgG subclass deficiency (Group 2) were compared. RESULTS: A total of 55 (49.54%) and 56 (50.45%) patients were included in Groups 1 and 2, respectively. Among our studied cases, 20 (18.1%) had a history of hospitalization in the neonatal period, 61 (54.95%) had at least one hospitalization due to infection, and 55 (49.54%) had a history of recurrent infection. The frequencies of these three conditions were statistically significantly higher in Group 2 (p < 0.05). The frequencies of infections in the last year in Groups 1 and 2 were 4.4 ± 1.2 and 5.4 ± 1.9, respectively (p < 0.05). As a result of recurrent infections, 43.24% (n = 48) of our patients received antibiotic prophylaxis, and 21.62% (n = 24) had immunoglobulin replacement therapy. Furthermore, the numbers of patients who needed these treatments were higher in Group 2 (p < 0.05). CONCLUSION: In cases with IgG subclass deficiencies, concomitant main-group immunoglobulin deficiencies may increase the number and severity of infections, leading to hospitalizations, antibiotic prophylaxis, and immunoglobulin therapy. More attention should be paid to cases of immunoglobulin main-group deficiencies in the follow-up of these cases.
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Deficiência de IgG , Reinfecção , Recém-Nascido , Criança , Humanos , Idoso , Reinfecção/complicações , Deficiência de IgG/diagnóstico , Deficiência de IgG/complicações , Imunoglobulina G , AntibioticoprofilaxiaRESUMO
Background: Inborn errors of immunity, mainly Predominantly Antibody deficiencies with normal IgG levels are unrecognized in adults with lung diseases such as bronchiectasis or recurrent pneumonia. Objective: To determine IgM, IgA, IgG2 subclass deficiencies, and Specific antibody deficiency (anti-pneumococcal polysaccharide antibodies) in adults with non-cystic fibrosis bronchiectasis or recurrent pneumonia. Methods: Cross-sectional study. Consecutive patients with non-cystic fibrosis bronchiectasis or recurrent pneumonia were recruited in Cali, Colombia. IgG, IgA, IgM, and IgE, IgG2subclass and IgG anti-pneumococcal serum levels were measured. Results: Among the 110 participants enrolled, Antibody deficiencies with normal serum IgG levels were found in 11(10%) cases. IgA deficiency (3 cases), IgM deficiency (2 cases) and IgG2 deficiency (2 cases) were the most frequent primary immunodeficiencies. In addition, IgG2+IgA deficiency, Ataxia-telangiectasia, Hyper-IgE syndrome and Specific Antibody Deficiency(anti-polysaccharides) were found in one case each. Conclusions: Predominantly antibody deficiencies with normal IgG levels are an important etiology of non-cystic fibrosis bronchiectasis and recurrent pneumonia in adults.
Antecedentes: Los Errores Innatos de la Inmunidad principalmente las Deficiencias Predominantemente de anticuerpos con niveles normales de IgG no se conocen en adultos con enfermedades pulmonares como las bronquiectasias o la neumonía recurrente. Objetivo: Determinar las deficiencias de IgM, IgA y de subclase de IgG2 y la Deficiencia Específica de Anticuerpos (anticuerpos antineumocócicos de polisacáridos) en adultos con Bronquiectasias no Fibrosis Quística (BQnoFQ) o neumonía recurrente. Métodos: Estudio observacional prospectivo. Se reclutaron 110 pacientes consecutivos con BQnoFQ o neumonía recurrente en Cali, Colombia. Se midieron los niveles séricos de IgG, IgA, IgM e IgE, subclase IgG2 y anticuerpos anti-neumococo. Resultados: Se encontraron deficiencias de anticuerpos con niveles normales de IgG en el 10% de los sujetos; Cuatro casos con IgG2 baja, incluido 1 caso de deficiencia de IgG2 + IgA, 1 caso de ataxia-telangiectasia, 3 deficiencias de IgA (IgAD), 2 deficiencias selectiva de IgM (IgMD), 1 síndrome de Hiper-IgE (HIES-AR) y 1 deficiencia específica de anticuerpos. Ocho pacientes fueron diagnosticados con enfermedades relacionadas con la hipogammaglobulinemia IgG. Conclusiones: Las deficiencias predominantemente de anticuerpos con niveles normales de IgG son una etiología importante de BQnoFQ y neumonía recurrente en adultos. Los sujetos con bronquiectasias o neumonía recurrente requieren una evaluación exhaustiva de la respuesta inmune humoral y clínica.
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Bronquiectasia , Deficiência de IgA , Deficiência de IgG , Síndromes de Imunodeficiência , Pneumonia , Adulto , Humanos , Estudos Transversais , Imunoglobulina G , Imunoglobulina M , Imunoglobulina A , FibroseRESUMO
BACKGROUND: Immunoglobulin G (IgG) deficiency increases the risk of acute exacerbations and mortality in chronic obstructive pulmonary disease (COPD). However, the impact of IgG subclass deficiency on mortality in COPD is unknown. Here, we determined which IgG subclass, if any, is associated with increased risk of mortality in COPD. METHODS: We measured serum IgG subclass concentrations of 489 hospitalized patients with COPD who were enrolled in the Rapid Transition Program (clinicaltrials.gov identifier NCT02050022). To evaluate the impact of IgG subclass deficiency on 1-year mortality, Cox proportional hazards regression analyses were performed with adjustments for potential confounders. RESULTS: Deficiencies in IgG1, IgG2, IgG3, and IgG4 were present in 1.8%, 12.1%, 4.3%, and 11.2% of patients, respectively. One-year mortality was 56% in patients with IgG1 deficiency, 27% in IgG2 deficiency, 24% in IgG3 deficiency, and 31% in IgG4 deficiency. Cox proportional modeling showed that IgG1 and IgG4 deficiencies increased the 1-year mortality risk with an adjusted hazard ratio of 3.92 (95% confidence interval [CI] = 1.55-9.87) and 1.74 (95% CI = 1.02-2.98), respectively. Neither IgG2 nor IgG3 deficiency significantly increased 1-year mortality. Two or more IgG subclass deficiencies were observed in 5.3%. Patients with 2 or more IgG subclass deficiencies had a higher 1-year mortality than those without any deficiencies (46.2% vs. 19.7%, p < 0.001), with an adjusted hazard ratio of 2.22 (95% CI = 1.18-4.17). CONCLUSIONS: IgG1 and IgG4 deficiency was observed in 1.8% and 11.2% of hospitalized patients with COPD, respectively, and these deficiencies were associated with a significantly increased risk of 1-year mortality.
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Deficiência de IgG , Síndromes de Imunodeficiência , Doença Pulmonar Obstrutiva Crônica , Humanos , Deficiência de IgG/diagnóstico , Imunoglobulina G , Doença Pulmonar Obstrutiva Crônica/diagnósticoRESUMO
Hydroxychloroquine (HCQ) therapy decreased immunoglobulin (Ig) levels in patients with Sjögren syndrome (SS) and rheumatoid arthritis (RA) in previous studies. We found no report of Ig levels of women with IgG subclass deficiency (IgGSD) and systemic lupus erythematosus (SLE), SS, or RA treated with HCQ. We retrospectively evaluated IgG, IgG subclass, IgA, and IgM levels and other characteristics of women at IgGSD diagnosis who did and did not take HCQ for SLE, SS, or RA. There were 132 women (48 subnormal IgG1 only, 49 combined subnormal IgG1/IgG3, and 35 subnormal IgG3 only). Mean age was 49 ± 13 years. Twenty-two women with SLE, SS, RA, or combination thereof reported HCQ ≥ 200 mg/day ≥ 6 months. In each IgGSD subtype, median Ig levels of women who took HCQ were not significantly lower than those of women who did not take HCQ. Women with combined subnormal IgG1/IgG3 who took HCQ had greater median IgG2 than women who did not take HCQ (4.89 g/L (range 4.43, 4.94) vs. 2.57 g/L (1.21, 6.44), respectively; p = 0.0123). Regressions on IgG1, IgG2, and IgG3 revealed positive associations with HCQ therapy (p = 0.0043, 0.0037, and 0.0139, respectively). There were no significant Ig associations with age, SLE, SS, or RA as independent variables. HCQ therapy of SLE, SS, or RA in women with IgGSD was not associated with significantly lower IgG, IgG subclass, IgA, or IgM levels. IgG1, IgG2, and IgG3 were positively associated with HCQ therapy, after adjustment for other variables.
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Artrite Reumatoide , Deficiência de IgG , Lúpus Eritematoso Sistêmico , Síndrome de Sjogren , Adulto , Artrite Reumatoide/tratamento farmacológico , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Imunoglobulina A , Imunoglobulina G , Imunoglobulina M , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Pessoa de Meia-Idade , Estudos Retrospectivos , Síndrome de Sjogren/tratamento farmacológicoRESUMO
INTRODUCTION: In secondary immunodeficiency, immunoglobulin replacement therapy (IgRT) is recommended by guidelines (GL) for patients with IgG level < 4 g/l and more than 3 infections or a severe infection. IgRT may be appropriate if IgG level < 4 g/l and/or 1-3 less severe infections (≤ grade 2). METHODS: This was a retrospective sample analysis representative for practices and hospitals in Germany. The treatments and infection data were collected from patients with chronic lymphocytic leukemia (CLL) and multiple myeloma (MM). GL adherence (GLAD) was analyzed. RESULTS: Data from 1086 patients (CLL 490, MM 596) were collected from 86 centers. Of all patients, 34.8% developed IgG deficiency during therapy (CLL 35.5%; MM 34.2%). IgRT was given in 23.5% of CLL and 14.4% of MM patients. GLAD in hypogammaglobulinemia and indication to IgRT was 23.3% of 86 CLL and 22.1% of 77 MM patients. Without GLAD, the hazard ratio (HR) for any infection was 4.49 (95% CI 3.72-5.42; p < 0.001) and for severe infections (grade ≥ 3) 10.64 (95% CI 7.54-15.00; p < 0.001). Significant independent risk factors for infections were a higher Charlson Comorbidity Index, IgG deficiency, and 3rd + line treatment, as well as therapy with BTK inhibitors or chemotherapy in CLL. Multivariable analysis showed a significantly lower risk of severe infections after start of IgRT with a HR of 0.47 (95% CI 0.28-0.77; p = 0.003). CONCLUSIONS: Guideline adherence correlated with fewer and less severe infections but was low in patients with indication to IgRT. Risk factors for infection can be identified. Risk of severe infections was significantly lower in patients with IgRT.
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Deficiência de IgG , Síndromes de Imunodeficiência , Leucemia Linfocítica Crônica de Células B , Mieloma Múltiplo , Fidelidade a Diretrizes , Humanos , Deficiência de IgG/complicações , Imunoglobulina G/uso terapêutico , Síndromes de Imunodeficiência/complicações , Síndromes de Imunodeficiência/tratamento farmacológico , Mieloma Múltiplo/complicações , Mieloma Múltiplo/terapia , Estudos RetrospectivosRESUMO
BACKGROUND: Immunoglobulin G (IgG) subclass 2 deficiency is the most frequent IgG subclass deficiency identified in patients with bronchiectasis, but its clinical significance is not known. AIM: To analyse if bronchiectasis patients with isolated IgG2 deficiency at risk of recurrent exacerbations and/or hospitalization? Do patients with IgG2 deficiency have worse disease progression? DESIGN AND METHODS: This is a retrospective study (2015-20) exploring independent risk factors for recurrent exacerbations (3 or more per year) and/or hospitalization with bronchiectasis exacerbations using multivariable models using binary logistic regression. There was no patient with IgG deficiency, IgG 1, 3 or 4 deficiency, or IgA or IgM deficiency included. In this model, the authors included: serum IgG2 level; lung function; body mass index; MRC breathlessness scale; age; sex; number of bronchiectatic lobes; bacterial colonization; comorbidities; and the use of long-term immunosuppressant drugs or antibiotics for more than 28 days. Analysing 2-year longitudinal data, one-way ANOVA and Mann-Whitney U-test were used to compare bronchiectasis severity between patients with different IgG2 levels. RESULTS: Serum IgG2 levels (<2.68 g/l, 2.68-3.53 g/l and 3.54-4.45 g/l); hospital admission in the preceding 2 years; bacterial colonization with potentially pathogenic organisms and asthma were independent predictors for three or more bronchiectasis exacerbations. Those with low IgG2 levels (<2.68 g/l and 2.68-3.53 g/l), had worsening progression of their bronchiectasis, using the Bronchiectasis Severity Index, over 1 year compared with those who were IgG2 replete (>4.45 g/l) (P = 0.003, 0.013). CONCLUSION: Reduced IgG2 levels were an independent predictor for bronchiectasis exacerbations and have increased disease progression.
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Bronquiectasia , Deficiência de IgG , Progressão da Doença , Humanos , Imunoglobulina G , Estudos Retrospectivos , Fatores de RiscoRESUMO
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).
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Ataxia Telangiectasia/imunologia , Ataxia Telangiectasia/mortalidade , Linfócitos B/imunologia , Deficiência de IgA/imunologia , Subpopulações de Linfócitos T/imunologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Deficiência de IgA/mortalidade , Deficiência de IgG/imunologia , Deficiência de IgG/mortalidade , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Lactente , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Background: Patients with antibody deficiency may experience exceptionally long diagnostic delays, increasing the risk of life-threatening infections, end-organ damage, mortality, and health costs. Objective: This study aimed to analyze serum protein electrophoresis and verify the correlation between calculated globulin (CG, total protein minus albumin levels) or electrophoretically determined serum gamma globulin fraction (Gamma) with IgG levels in children and adolescents under 18 years old (yo). Methods: We analyzed serum protein electrophoresis (GC or Gamma) and IgG levels from 1215 children and adolescents under 18 yo, classified into 5 age groups. We verified the correlation between CG or Gamma with serum IgG levels. Results: Serum IgG levels varied according to age groups (from 4.3 ± 2.3 g/l in children under 6 months old to 11.4 ± 3.2 g/l in adolescents in the 10-<18 yo group). CG sensitivity and specificity to detect IgG below the reference range for all patients were 93.1% and 81.8%, respectively, and varied according to age group. Gamma sensitivity and specificity for all patients were 100% and 87.8%, respectively, and varied according to age group as well. We found serum IgG levels below the age reference level in 29 patients (2.4% of the cases) using CG or Gamma levels. Conclusion: Both CG and Gamma levels may be of utility as a screening tool for earlier diagnosis of antibody deficiency in children and adolescents under 18 yo.
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Anticorpos/sangue , Eletroforese das Proteínas Sanguíneas , Disgamaglobulinemia/diagnóstico , Programas de Rastreamento/métodos , Adolescente , Fatores Etários , Área Sob a Curva , Brasil/epidemiologia , Criança , Pré-Escolar , Disgamaglobulinemia/sangue , Disgamaglobulinemia/epidemiologia , Disgamaglobulinemia/imunologia , Feminino , Humanos , Deficiência de IgA/sangue , Deficiência de IgA/diagnóstico , Deficiência de IgG/sangue , Deficiência de IgG/diagnóstico , Imunoglobulina M/sangue , Imunoglobulina M/deficiência , Lactente , Recém-Nascido , Masculino , Curva ROC , Soroglobulinas/análiseRESUMO
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.
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Doenças Autoimunes/imunologia , Deficiência de IgG/imunologia , Imunoglobulina G/genética , Isotipos de Imunoglobulinas/genética , Adulto , Idoso , Doenças Autoimunes/epidemiologia , Feminino , Humanos , Deficiência de IgG/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Soroepidemiológicos , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: The innate and adaptive immune system is involved in the airway inflammation associated with acute exacerbations in patients with chronic obstructive pulmonary disease (COPD). We evaluated the association of mannose-binding lectin (MBL), immunoglobulin (Ig) and ficolin-2 concentrations with COPD exacerbations and according to the glucocorticoid treatment duration for an index exacerbation. METHODS: Post-hoc analysis of the randomized, double-blind, placebo-controlled REDUCE trial of 5 vs. 14 days of glucocorticoid treatment for an index exacerbation. MBL, ficolin-2 and total IgG/IgA and subclass concentrations were determined in stored samples drawn (n = 178) 30 days after the index exacerbation and associated with the risk of re-exacerbation during a 180-day follow-up period. RESULTS: IgG and subclass concentrations were significantly lower after 14 days vs. 5 days of glucocorticoid treatment. Patients with higher MBL concentrations were more likely to suffer from a future exacerbation (multivariable hazard ratio 1.03 per 200 ng/ml increase (95% confidence interval (CI) 1.00-1.06), p = 0.048), whereas ficolin-2 and IgG deficiency were not associated. The risk was most pronounced in patients with high MBL concentrations, IgG deficiency and 14 days of glucocorticoid treatment pointing towards an interactive effect of MBL and IgG deficiency in the presence of prolonged glucocorticoid treatment duration [Relative excess risk due to interaction 2.13 (95% CI - 0.41-4.66, p = 0.10)]. IgG concentrations were significantly lower in patients with frequent re-exacerbations (IgG, 7.81 g/L vs. 9.53 g/L, p = 0.03). CONCLUSIONS: MBL modified the short-term exacerbation risk after a recent acute exacerbation of COPD, particularly in the setting of concurrent IgG deficiency and recent prolonged systemic glucocorticoid treatment. Ficolin-2 did not emerge as a predictor of a future exacerbation risk.
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Progressão da Doença , Imunoglobulina G/sangue , Lectinas/sangue , Lectina de Ligação a Manose/sangue , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Método Duplo-Cego , Feminino , Seguimentos , Previsões , Humanos , Deficiência de IgG/sangue , Deficiência de IgG/diagnóstico , Masculino , Pessoa de Meia-Idade , Fatores de Risco , FicolinasRESUMO
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.
Assuntos
Imunodeficiência de Variável Comum/imunologia , Imunodeficiência de Variável Comum/terapia , Deficiência de IgG/imunologia , Deficiência de IgG/terapia , Vacinas Pneumocócicas/uso terapêutico , Adulto , Idoso , Anticorpos Antibacterianos/sangue , Especificidade de Anticorpos , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/classificação , Masculino , Pessoa de Meia-Idade , Fagocitose/imunologia , Infecções Pneumocócicas/imunologia , Infecções Pneumocócicas/prevenção & controle , Sorogrupo , Streptococcus pneumoniae/classificação , Streptococcus pneumoniae/imunologia , Fatores de Tempo , Vacinas Conjugadas/uso terapêutico , Adulto JovemRESUMO
Primary antibody deficiencies (PAD) are the most prevalent group of primary immunodeficiencies (PID) in adults and immunoglobulin replacement therapy (IRT) is the mainstay therapy to improve clinical outcomes. IRT is, however, expensive and, in minor PAD, clear recommendations concerning IRT are lacking. We conducted a retrospective real-life study to assess the effectiveness of low-dose IRT in minor PAD on 143 patients fulfilling European Society for Immunodeficiencies (ESID) diagnostic criteria for immunoglobulin (Ig)G subclass deficiency (IgGSD) or unclassified antibody deficiency (UAD). All patients were treated with intravenous low-dose IRT (0.14 ± 0.06 g/kg/month). Immunoglobulin (Ig) classes and IgG subclasses were measured at baseline and after 1 year of IRT. The annual rate of total infections, upper respiratory tract infections (URTI), lower respiratory tract infections (LRTI) and hospitalizations was measured at baseline and after 1 and 2 years of IRT. After 1 year of IRT significant improvement was demonstrated in: (a) serum IgG (787.9 ± 229.3 versus 929.1 ± 206.7 mg/dl; p < 0.0001); (b) serum IgG subclasses (IgG1 = 351.4 ± 109.9 versus 464.3 ± 124.1, p < 0.0001; IgG2 = 259.1 ± 140 versus 330.6 ± 124.9, p < 0.0001; IgG3 = 50.2 ± 26.7 versus 55.6 ± 28.9 mg/dl, p < 0.002); (c) annual rate of total infections (5.75 ± 3.87 versus 2.13 ± 1.74, p < 0.0001), URTI (1.48 ± 3.15 versus 0.69 ± 1.27; p < 0.005), LRTI (3.89 ± 3.52 versus 1.29 ± 1.37; p < 0.0001) and hospitalizations (0.37 ± 0.77 versus 0.15 ± 0.5; p < 0.0002). The improvement persisted after 2 years of IRT. No significant improvement in URTI annual rate was noted in UAD and in patients with bronchiectasis. In conclusion, low-dose IRT can improve clinical outcomes in UAD and IgGSD patients, providing a potential economical advantage over the standard IRT dose.
Assuntos
Deficiência de IgG/terapia , Imunoglobulina G/administração & dosagem , Imunoglobulinas Intravenosas/uso terapêutico , Doenças da Imunodeficiência Primária/terapia , Idoso , Bronquiectasia/complicações , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Infecções Respiratórias/epidemiologia , Estudos RetrospectivosAssuntos
Deficiência de IgG/imunologia , Imunoglobulina G/imunologia , Doença Pulmonar Obstrutiva Crônica/imunologia , Infecções Respiratórias/imunologia , Agamaglobulinemia/epidemiologia , Agamaglobulinemia/imunologia , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Humanos , Deficiência de IgG/epidemiologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Doença Pulmonar Obstrutiva Crônica/mortalidade , Infecções Respiratórias/epidemiologiaRESUMO
BACKGROUND: Type 1 diabetes (T1D) may coexist with primary immunodeficiencies, indicating a shared genetic background. OBJECTIVE: To evaluate the prevalence and clinical characteristics of immunoglobulin deficiency (IgD) among children with T1D. METHODS: Serum samples and medical history questionnaires were obtained during routine visits from T1D patients aged 4-18 years. IgG, IgA, IgM, and IgE were measured by nephelometry and enzyme-linked immunosorbent assay (ELISA). IgG and IgM deficiency (IgGD, IgMD) were defined as IgG/IgM >2 standard deviations (SD) below age-adjusted mean. IgE deficiency was defined as IgE <2 kIU/L. IgA deficiency (IgAD) was defined as IgA >2 SD below age-adjusted mean irrespective of other immunoglobulin classes (absolute if <0.07 g/L, partial otherwise) and as selective IgAD when IgA >2 SD below age-adjusted mean with normal IgG and IgM (absolute if <0.07 g/L, partial otherwise). RESULTS: Among 395 patients (53.4% boys) with the median age of 11.2 (8.4-13.7) and diabetes duration 3.6 (1.1-6.0) years, 90 (22.8%) were found to have hypogammaglobulinemia. The IgGD and IgAD were the most common each in 40/395 (10.1%). Complex IgD was found in seven patients. Increased odds of infection-related hospitalization (compared to children without any IgD) was related to having any kind of IgD and IgAD; OR (95%CI) = 2.1 (1.2-3.7) and 3.7 (1.8-7.5), respectively. Furthermore, IgAD was associated with having a first-degree relative with T1D OR (95%CI) = 3.3 (1.4-7.6) and suffering from non-autoimmune comorbidities 3.3 (1.4-7.6), especially neurological disorders 3.5 (1.2-10.5). CONCLUSIONS: IgDs frequently coexist with T1D and may be associated with several autoimmune and nonimmune related disorders suggesting their common genetic background.
Assuntos
Diabetes Mellitus Tipo 1 , Síndromes de Imunodeficiência , Adolescente , Idade de Início , Criança , Estudos de Coortes , Diabetes Mellitus Tipo 1/classificação , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/patologia , Feminino , Humanos , Deficiência de IgG/complicações , Deficiência de IgG/epidemiologia , Deficiência de IgG/patologia , Imunoglobulina A/análise , Imunoglobulina A/sangue , Imunoglobulina G/análise , Imunoglobulina G/sangue , Síndromes de Imunodeficiência/classificação , Síndromes de Imunodeficiência/complicações , Síndromes de Imunodeficiência/epidemiologia , Síndromes de Imunodeficiência/patologia , Masculino , Fenótipo , Polônia/epidemiologia , PrevalênciaAssuntos
Asma/imunologia , COVID-19/imunologia , Imunodeficiência de Variável Comum/imunologia , Deficiência de IgG/imunologia , Obesidade Mórbida/imunologia , Infecções Estafilocócicas/imunologia , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Adulto , Alanina/análogos & derivados , Alanina/uso terapêutico , Antivirais/uso terapêutico , Asma/patologia , Asma/terapia , Asma/virologia , COVID-19/patologia , COVID-19/terapia , COVID-19/virologia , Imunodeficiência de Variável Comum/patologia , Imunodeficiência de Variável Comum/terapia , Imunodeficiência de Variável Comum/virologia , Evolução Fatal , Humanos , Deficiência de IgG/patologia , Deficiência de IgG/terapia , Deficiência de IgG/virologia , Imunização Passiva , Imunoglobulina G/sangue , Imunoglobulinas Intravenosas/uso terapêutico , Masculino , Staphylococcus aureus Resistente à Meticilina , Obesidade Mórbida/patologia , Obesidade Mórbida/terapia , Obesidade Mórbida/virologia , SARS-CoV-2 , Infecções Estafilocócicas/patologia , Infecções Estafilocócicas/terapia , Infecções Estafilocócicas/virologia , Soroterapia para COVID-19RESUMO
Recurrent respiratory tract infections (RTI) are one of the most common diseases in childhood. Frequent infections adversely affect the development of a child and may lead to suspicion of immunodeficiency. An additional allergy component is thought conducive to infection occurrence. In this study, we retrospectively assessed medical records of 524 children hospitalized with RTI. Patients were divided into two groups: RTI-alone (n = 394) and RTI with a history of allergy (n = 130). Overall, we found that a great majority of children with RTI had the immunoglobulin G within the normal limit, irrespective of allergy. A variable IgG deficiency, most often affecting IgG1, IgG3, and IgG4 subclass, was present in less than one-third of children. Proportions of specific IgG subclass deficiency, varying from about 10% to 40%, were similar in both RTI-alone and RTI-allergy groups. The only significant effect was a modestly smaller proportion of children with IgG4 deficiency in the RTI-allergy group when compared with the RTI-alone group. We also found that IgG deficiencies were age-dependent as their number significantly increased with children's age, irrespective of allergy. The results demonstrate a lack of distinct abnormalities in the immunoglobulin G profile which would be characteristic to a clinical history of allergy accompanying recurrent RTI in children. Thus, we conclude that the assessment of IgGs could hardly be of help in the differential diagnostics of the allergic background of RTI.