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BMC Immunology Aug 2021Factors associated with IgG levels in adults with IgG subclass deficiency (IgGSD) are incompletely understood. We studied adults with IgGSD with subnormal IgG1 only,...
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.
Topics: Adult; Aged; Autoimmune Diseases; Female; Humans; IgG Deficiency; Immunoglobulin G; Immunoglobulin Isotypes; Male; Middle Aged; Seroepidemiologic Studies; United States
PubMed: 34372773
DOI: 10.1186/s12865-021-00447-3 -
Pediatrics and Neonatology Jan 2023IgG subclass deficiency is a laboratory diagnosis and becomes important with recurrent infections. This study aimed to examine the demographic, clinical, and laboratory...
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.
Topics: Infant, Newborn; Child; Humans; Aged; Reinfection; IgG Deficiency; Immunoglobulin G; Antibiotic Prophylaxis
PubMed: 36089538
DOI: 10.1016/j.pedneo.2022.04.014 -
The Journal of Allergy and Clinical... Apr 2019Common variable immunodeficiency (CVID) and IgG deficiency are 2 of the more prevalent primary humoral immune defects. The former is defined by consensus with criteria... (Comparative Study)
Comparative Study
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.
Topics: Autoimmune Diseases; B-Lymphocyte Subsets; B-Lymphocytes; Bronchiectasis; Cohort Studies; Common Variable Immunodeficiency; Female; Flow Cytometry; Humans; IgG Deficiency; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Immunologic Memory; Immunophenotyping; Lymphocyte Count; Male; Middle Aged; Pneumonia; Serologic Tests; Sinusitis; T-Lymphocytes; Vaccines
PubMed: 30557717
DOI: 10.1016/j.jaip.2018.12.004 -
Annals of Allergy, Asthma & Immunology... Aug 2020Serum immunoglobulin G (IgG) concentrations are integral to the workup of immune deficiencies and IgG4-related disease (IgG4-RD). Demographic differences in IgG...
BACKGROUND
Serum immunoglobulin G (IgG) concentrations are integral to the workup of immune deficiencies and IgG4-related disease (IgG4-RD). Demographic differences in IgG concentrations are poorly described but can influence test interpretation, contribute to racial disparities in primary immunodeficiency diagnosis, and explain demographic differences in IgG concentrations in IgG4-RD.
OBJECTIVE
To assess differences in IgG and IgG subclass concentrations according to sex and race.
METHODS
We identified patients with IgG and IgG subclass concentrations measured in a large health care system. Multivariate-adjusted differences in IgG and IgG subclass concentrations and the proportion of subjects with results outside of reference ranges according to sex and race were estimated.
RESULTS
Of the 12,851 patients, the mean age was 54.7 years and 7917 (62%) were female. Of these, 11,673 (91%) were white, 611 (5%) were black, and 302 (2%) were Asian. Compared with the mean concentrations of white patients, Asian and black patients had higher mean concentrations of IgG (1340.0 and 1504.4 vs 988.1 mg/dL, P < .001), IgG1 (782.0 and 938.4 vs 592.4 mg/dL, P < .001), IgG2 (493.5 and 384.2 vs 305 mg/dL, P < .001), IgG3 (76.6 and 91.9 vs 55.9 mg/dL, P < .001), and IgG4 (140.4 and 53.6 vs 41.6 mg/dL, P < .001). Immunoglobin G subclass 4 concentrations were higher in males than those in females (56.3 vs 37.4 mg/dL, P < .001). Similar observations were made when comparing the proportions of patients with results outside of reference ranges and after stratifying by diagnosis.
CONCLUSION
Immunoglobin G and IgG subclass concentrations differ according to sex and race. These findings may have implications for the interpretation of these test results but require confirmation in diverse, healthy populations.
Topics: Adult; Aged; Aged, 80 and over; Cohort Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; IgG Deficiency; Immunoglobulin G; Immunoglobulin G4-Related Disease; Immunoglobulin Isotypes; Male; Middle Aged; Race Factors; Sex Factors
PubMed: 32224206
DOI: 10.1016/j.anai.2020.03.018 -
Japanese Journal of Infectious Diseases May 2022The prevalence and mortality rates of coronavirus disease 2019 (COVID-19) widely vary among populations. Mucosal immunity is the first barrier to the pathogen's entry...
The prevalence and mortality rates of coronavirus disease 2019 (COVID-19) widely vary among populations. Mucosal immunity is the first barrier to the pathogen's entry into the body. Immunoglobulin A (IgA) is the primary antibody responsible for mucosal immunity. We explored the relationship between selective IgA deficiency (SIgAD) and COVID-19 severity. We included 424 patients (203 women) with COVID-19. Eleven patients had SIgAD. Laboratory data of patients with SIgAD and normal IgA levels were compared. The relationship between SIgAD and severe COVID-19 infection was explored using logistic regression analysis. In the univariate logistic regression analysis, the risk of severe COVID-19 disease in patients with SIgAD was approximately 7.7-fold higher than that in other patients (odds ratio [OR], 7.789; 95% confidence interval [CI], 1.665-36.690, P = 0.008), while it was 4-fold (OR, 4.053; 95% CI, 1.182-13.903, P = 0.026) higher in the multivariate logistic regression analysis. Serum IgA levels were positively correlated with total lymphocyte counts and negatively correlated with C-reactive protein levels, which was a risk factor for severe COVID-19. In patients with SIgAD, the number of severe acute respiratory coronaviruses 2 that pass through mucosal membranes may be increased, leading to complications such as cytokine storm syndrome and acute respiratory distress syndrome.
Topics: COVID-19; Female; Humans; IgA Deficiency; Immunoglobulin A; Prognosis
PubMed: 34588364
DOI: 10.7883/yoken.JJID.2021.281 -
The Pan African Medical Journal 2014
Review
Topics: Agammaglobulinemia; Humans; IgA Deficiency; IgG Deficiency; Immunity, Humoral; Immunologic Deficiency Syndromes
PubMed: 25489366
DOI: 10.11604/pamj.2014.18.272.4061 -
Anales de Pediatria Sep 2022(1) To describe the prevalence of IgA deficiency (IgAD), uveitis, coeliac disease (CD) and thyroid disorders in a multicentric cohort of patients diagnosed with JIA and,...
OBJECTIVES
(1) To describe the prevalence of IgA deficiency (IgAD), uveitis, coeliac disease (CD) and thyroid disorders in a multicentric cohort of patients diagnosed with JIA and, (2) to evaluate whether patients with JIA and IgAD present other autoimmune diseases more frequently than patients with normal serum levels of IgA.
METHODS
Retrospective chart review of a cohort of patients diagnosed with JIA followed at the paediatric rheumatology units of two hospitals in Madrid, Spain.
RESULTS
A total of 193 patients were included. Of them, 123 were females (64%). Median age at disease onset was 5.6 years (IQR 2.5-9.7) and the median time of follow-up was 5.1 years (IQR 2.2-8.1). The three most common ILAR categories were oligoarticular (53%), polyarticular RF negative (20%) and enthesitis related arthritis (10%). Serum IgA levels were available in 172/193 (89%); 25/172 (15%) had selective (<7mg/dl, n=8) or partial (7-69mg/dl, n=17) IgAD. All the patients had periodic eye exams. Eighteen children (9%) had anterior uveitis, 15/18 chronic and 3/18 acute. Serum anti transglutaminase IgA, or IgG in IgAD were obtained in 135/193 (70%). Four children (3%) were diagnosed with CD either by intestinal biopsy (n=3) or by the combination of characteristic clinical, serological and genetic features (n=1); two of them had IgAD (p=0.12; OR=6.4; 95% CI 0.9-47.6). Only 1/153 (0.7%) patient had hyperthyrotropinemia with positive anti-thyroid antibodies and required replacement therapy.
CONCLUSION
Patients with JIA frequently present autoimmune comorbidities. IgAD does not seem to increase their prevalence, with the possible exception of CD.
Topics: Arthritis, Juvenile; Celiac Disease; Child; Child, Preschool; Female; Humans; IgA Deficiency; Immunoglobulin A; Male; Retrospective Studies; Transglutaminases
PubMed: 35459637
DOI: 10.1016/j.anpede.2022.03.004 -
The Journal of Clinical Investigation Jan 2020X-linked immunodeficiency with magnesium defect, EBV infection, and neoplasia (XMEN) disease are caused by deficiency of the magnesium transporter 1 (MAGT1) gene. We...
X-linked immunodeficiency with magnesium defect, EBV infection, and neoplasia (XMEN) disease are caused by deficiency of the magnesium transporter 1 (MAGT1) gene. We studied 23 patients with XMEN, 8 of whom were EBV naive. We observed lymphadenopathy (LAD), cytopenias, liver disease, cavum septum pellucidum (CSP), and increased CD4-CD8-B220-TCRαβ+ T cells (αβDNTs), in addition to the previously described features of an inverted CD4/CD8 ratio, CD4+ T lymphocytopenia, increased B cells, dysgammaglobulinemia, and decreased expression of the natural killer group 2, member D (NKG2D) receptor. EBV-associated B cell malignancies occurred frequently in EBV-infected patients. We studied patients with XMEN and patients with autoimmune lymphoproliferative syndrome (ALPS) by deep immunophenotyping (32 immune markers) using time-of-flight mass cytometry (CyTOF). Our analysis revealed that the abundance of 2 populations of naive B cells (CD20+CD27-CD22+IgM+HLA-DR+CXCR5+CXCR4++CD10+CD38+ and CD20+CD27-CD22+IgM+HLA-DR+CXCR5+CXCR4+CD10-CD38-) could differentially classify XMEN, ALPS, and healthy individuals. We also performed glycoproteomics analysis on T lymphocytes and show that XMEN disease is a congenital disorder of glycosylation that affects a restricted subset of glycoproteins. Transfection of MAGT1 mRNA enabled us to rescue proteins with defective glycosylation. Together, these data provide new clinical and pathophysiological foundations with important ramifications for the diagnosis and treatment of XMEN disease.
Topics: Antigens, CD; Autoimmune Lymphoproliferative Syndrome; CD4-CD8 Ratio; Cation Transport Proteins; Female; Glycosylation; Humans; Magnesium Deficiency; Male; X-Linked Combined Immunodeficiency Diseases
PubMed: 31714901
DOI: 10.1172/JCI131116 -
Archives of Iranian Medicine Feb 2021
Topics: Child; Common Bile Duct; Cryptosporidiosis; Humans; Hyper-IgM Immunodeficiency Syndrome; Male
PubMed: 33636981
DOI: 10.34172/aim.2021.20 -
Frontiers in Immunology 2018DiGeorge syndrome is an immunodeficiency characterized by thymic dysplasia resulting in T cell lymphopenia. Most patients suffer from increased susceptibility to...
DiGeorge syndrome is an immunodeficiency characterized by thymic dysplasia resulting in T cell lymphopenia. Most patients suffer from increased susceptibility to infections and heightened prevalence of autoimmune disorders, such as autoimmune thrombocytopenia. B cells in DiGeorge syndrome show impaired maturation, with low switched-memory B cells and a wide spectrum of antibody deficiencies or dysgammaglobulinemia, presumably due to impaired germinal center responses. We set out to evaluate circulating follicular helper T cells (cTFHs) in DiGeorge syndrome, as markers of T-B interaction in the germinal centers in a cohort of 17 patients with partial DiGeorge and 21 healthy controls of similar age. cTFHs were characterized as CXCR5CD45RA CD4 T cells using flow cytometry. We verify previous findings that the population of memory CD4 T cells is relatively increased in diGeorge patients, corresponding to low naïve T cells and impaired T cell production in the thymus. The population of CXCR5 memory CD4 T cells (cTFHs) was significantly expanded in patients with DiGeorge syndrome, but only healthy controls and not DiGeorge syndrome patients showed gradual increase of CXCR5 expression on cTFHs with age. We did not observe correlation between cTFHs and serum IgG levels or population of switched memory B cells. There was no difference in cTFH numbers between DiGeorge patients with/without thrombocytopenia and with/without allergy. Interestingly, we show strong decline of PD1 expression on cTFHs in the first 5 years of life in DiGeorge patients and healthy controls, and gradual increase of PD1 and ICOS expression on CD4 T cells in healthy controls later in life. Thus, here, we show that patients with DiGeorge syndrome have elevated numbers of cTFHs, which, however, do not correlate with autoimmunity, allergy, or production of immunoglobulins. This relative expansion of cTFH cells may be a result of impaired T cell development in patients with thymic dysplasia.
PubMed: 30083170
DOI: 10.3389/fimmu.2018.01730