IgG subclasses in smokers with chronic bronchitis and recurrent exacerbations

BACKGROUNDTobacco smokers have lower serum levels of IgG than non-smokers. IgG subclass deficiency is common in patients with recurrent respiratory infections. Recurrent bronchial infections are common in smokers with chronic bronchitis (CB). We have investigated whether susceptibility to recurrent exacerbations in smokers with CB is associated with altered IgG subclass levels or IgG subclass deficiency.METHODSSerum levels of IgG, IgA, IgM, and IgG subclasses 1–4 were determined by radial immunodiffusion in 100 subjects: 33 smokers with stable CB and recurrent exacerbations, 24 asymptomatic smokers, and 43 healthy never smokers. Systemic tobacco exposure was verified and excluded using a serum cotinine ELISA. Immunoglobulin data were log transformed to enable use of parametric statistical methods.RESULTSCompared with never smokers, both patients with CB and asymptomatic smokers had significantly lower levels of IgG (median 9.7 g/l (range 5.6–15.2) and 9.9 (6.1–12.1) g/l v 12.0 (6.9–18.5) g/l) and IgG2 (2.8 (0.9–5.9) g/l and 2.5 (1.0–6.3) g/lv 4.0 (1.7–10.2) g/l). The estimated ratio of median values between the patients with CB and never smokers was 0.78 (95% confidence interval (CI) 0.69 to 0.89) for IgG and 0.65 (95% CI 0.50 to 0.83) for IgG2. The corresponding ratios between asymptomatic smokers and never smokers were 0.79 (95% CI 0.69 to 0.91) and 0.60 (95% CI 0.50 to 0.83), respectively. There were no significant differences between the smoking groups.CONCLUSIONSSusceptibility to recurrent exacerbations in smokers with CB is not associated with lower levels of IgG subclasses than can be accounted for by smoking per se.

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Coexistence of (Partial) Immune Defects and Risk of Recurrent Respiratory Infections

Clinical Chemistry ◽

10.1373/clinchem.2007.075861 ◽

2007 ◽

Vol 53 (1) ◽

pp. 124-130 ◽

Cited By ~ 37

Author(s):

Xavier Bossuyt ◽

Leen Moens ◽

Erna Van Hoeyveld ◽

Axel Jeurissen ◽

Guy Bogaert ◽

...

Keyword(s):

Antibody Response ◽

Respiratory Infections ◽

Lymphocyte Subset ◽

Igg Subclass ◽

Promoter Polymorphisms ◽

Igg Subclass Deficiency ◽

Recurrent Respiratory Infections ◽

C4 Deficiency ◽

Subclass Deficiency ◽

Immune Defects

Abstract Background: Respiratory infections are major causes of morbidity and mortality, but determinants of susceptibility are poorly defined. We studied whether and to what extent immunologic and genetic factors are associated with increased susceptibility to respiratory infections. Methods: We evaluated the prevalence of IgA, IgM, IgG, and IgG subclass deficiencies, impairment in the antibody response against pneumococcal polysaccharides, G2m(n) allotypes, FcγRIIa polymorphisms, partial C2 and partial C4 deficiency, promoter polymorphisms in MBL2, and lymphocyte subset deficiencies in a control population and in consecutive children with recurrent respiratory infections. Results: IgA and/or IgG subclass deficiency was found in 27 of 55 patients (49%) and 6 of 43 controls (14%) (P = 0.0006). An impaired antibody response to polysaccharides was found in 7 patients (19%) and in 0 of 37 controls (P = 0.002). The Gm(n)marker was absent in 25 of 55 patients (45%) and 6 of 42 controls (14%) (P = 0.009). The MBL2 variants O/O, A/O, and A/A occurred in 9, 14, and 32 of the 55 patients, respectively, and in 1, 19, and 23 of the 43 controls, respectively (P = 0.05). There was no increase in the prevalence of partial C4 deficiency, C2 deficiency, lymphocyte subset deficiency, or FcγRIIa polymorphism in the patients compared to the controls. A combination of at least 2 immune defects was found in 31 of 55 patients (56%) and in 4 of 42 controls (11.6%) (P <0.0001). Conclusion: Specific antipolysaccharide antibody deficiency, IgA and/or IgG subclass deficiency, Gm(n) allotype, and MBL2 genotype are susceptibility factors for recurrent respiratory infections, and coexistence of several immune defects is the strongest risk factor in this study.

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IgG Subclass Deficiency in Children with IgA Deficiency Presenting with Recurrent or Severe Respiratory Infections

Pediatric Research ◽

10.1203/00006450-198610000-00006 ◽

1986 ◽

Vol 20 (10) ◽

pp. 937-942 ◽

Cited By ~ 34

Author(s):

Lorraine J Beard ◽

Antonio Ferrante ◽

Vivi-Anne Oxelius ◽

George M Maxwell

Keyword(s):

Respiratory Infections ◽

Iga Deficiency ◽

Igg Subclass ◽

Igg Subclass Deficiency ◽

Subclass Deficiency

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Disorders of Humoral Immunity in Children with IgG Subclass Deficiency and Recurrent Respiratory Infections

Advances in Experimental Medicine and Biology - Current Trends in Immunity and Respiratory Infections ◽

10.1007/5584_2018_263 ◽

2018 ◽

pp. 99-106 ◽

Cited By ~ 4

Author(s):

Gerard Pasternak ◽

Aleksandra Lewandowicz-Uszyńska ◽

Katarzyna Pentoś

Keyword(s):

Humoral Immunity ◽

Respiratory Infections ◽

Igg Subclass ◽

Igg Subclass Deficiency ◽

Recurrent Respiratory Infections ◽

Subclass Deficiency

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Immunoglobulin G (IgG) Subclasses in Chronic Lymphocytic Leukaemia

Blood ◽

10.1182/blood.v112.11.4180.4180 ◽

2008 ◽

Vol 112 (11) ◽

pp. 4180-4180

Author(s):

Jane A. Freeman ◽

Cecily J. Forsyth ◽

Naomi J. Mackinlay ◽

Ping Han ◽

Stephen P. Mulligan

Keyword(s):

Chronic Lymphocytic Leukaemia ◽

Lymphocytic Leukaemia ◽

Clinical Stage ◽

Recurrent Infection ◽

Igg Subclasses ◽

Igg Subclass ◽

Igg Subclass Deficiency ◽

Subclass Deficiency ◽

Intravenous Gammaglobulin ◽

Immunoglobulin Levels

Abstract Hypogammaglobulinaemia is a common complication of Chronic Lymphocytic Leukaemia (CLL) with an incidence that varies considerably in the reported literature. Immunoglobulin replacement therapy has documented benefit for patients with hypogammaglobulinaemia, CLL and recurrent episodes of infection. Very little data exists on IgG subclasses in CLL. We measured IgG subclasses together with immunoglobulins G, A and M, protein EPG and immunofixation in a cohort of patients with CLL representing a variety of disease stages, treatment status and history of infection to analyse the implications of IgG subclass deficiency in the disease. There were 155 patients analysed with 89 males and 66 females with mean age 67.4 (range 21–95) years. Distribution by Binet Stage was A-107, B-38, C-10. There were 111 patients untreated and 44 who had received chemotherapy, 21 with fludarabine based therapy and 11 containing rituximab (all FCR, 2 with lumiliximab). Five patients had received prior intravenous gammaglobulin (IVIg) and were excluded from further analysis. In the remaining 150 patients with no exposure to IVIg, low immunoglobulin levels were as follows: IgG <6.0g/L–46 (30.6%); IgA <0.69g/L–46 (30.6%); IgM <0.5g/L-87 (58%). IgG subclass deficiency were as follows: IgG1 <4.0g/L-39; IgG2<1.3g/L-28; IgG3 <0.4g/L-79; IgG4 <0.05g/L–35, with a total of 97/150 patients (64.6%) having a deficiency of at least one IgG subclass defined at these levels. IgG subclass deficiency was seen in 52 patients with a normal total IgG level ≥6.0g/L. Entirely normal immunoglobulin levels (IgG, A, M and IgG subclass) were seen in only 26 patients, none of these patients had recurrent infection. Recurrent episodes of infection were seen in 24 patients of whom 13 had total IgG <6.0g/L. Recurrent infection with total IgG≥6.0g/L was seen in 11 patients. The incidence by clinical stage of infection and IgG subclass deficiency are shown in the table. Stage No patients Infection % infection No IgG subclass deficiency. A 106 10 yes 4% All (100%) 96 no 50 (52%) B 37 11 yes 29.7% All (100%) 26 no 19 (73%) C 7 3 yes 43% All (100%) 4 no All (100%) Chemotherapy exposure correlated strongly with clinical stage and disease progression and a separate treatment effect could not be discriminated in this series. Paraproteins were seen in 24 patients, 14 IgG, (3 IgG1, 2 IgG4, others indeterminate), 6 IgA and 4 IgM. Polyclonal hypergammaglobulinaemia was present in 5 patients, 3 of whom had predominantly an increased IgG2. There were 19/129 (14.7%) patients with a positive Coombs’ test (direct antiglobulin test-DAT), all of whom had at least one immunoglobulin abnormality; 12 a total IgG <6.0g/L, 16 at least one IgG subclass deficiency and 6 paraproteins. Analysis of immunoglobulin levels and IgG subclasses in a cohort of patients with variety of clinical stage shows IgG subclass deficiency is common, especially in advanced Stage B and C disease. All combinations of IgG subclass deficiency may be seen in CLL. IgG subclass deficiency (64.6%) is more common than low total IgG (30.6%) and the rate of infection (16%). Abnormal immunoglobulin levels appear associated with a positive DAT (100%). Paraproteins were seen in 16% of patients.

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Factors associated with IgG levels in adults with IgG subclass deficiency

BMC Immunology ◽

10.1186/s12865-021-00447-3 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

James C. Barton ◽

Jackson Clayborn Barton ◽

Luigi F. Bertoli ◽

Ronald T. Acton

Keyword(s):

Igg Subclasses ◽

Igg Subclass ◽

Igg Subclass Deficiency ◽

Factors Associated ◽

Independent Variables ◽

Percentage Difference ◽

Autoimmune Condition ◽

Subclass Deficiency ◽

Igg1 Subclass ◽

Age And Sex

Abstract 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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