Immunological studies on bee-keepers: Specific IgG and subclass typing IgG against bee venom and bee venom components

Summary Specific IgE antibodies against bee venom and its components were studied in 23 bee-keepers. The highest IgG serum levels were observed for whole bee venom followed by phospholipase A. The serum levels of specific IgG antibodies against melittin and MCD-peptide were lower, the lowest serum levels being observed for apamin. After a 5 month absence from bee-keeping a fall in the serum levels of IgG antibodies was observed in all the bee-keepers studied. The investigation of the IgG subclass antibodies 1–4 against bee venom and phospholipase A demonstrated the highest serum levels for IgG 4 and IgG 2, the lowest levels were observed for IgG 1. The lowest IgG serum levels were associated with the least effective protection to bee stings. These findings support the concept that specific IgG antibodies prevent the development of allergic symptoms after bee sting.This study was supported by Deutsche Forschungsgemeinschaft, grant Ur 12/2-3     

Usefulness of measuring serum IgG4 level as diagnostic and treatment marker in IgG4-related disease

IgG4-related disease is a chronic disorder, which is characterized with elevated levels of serum immunoglobulin (Ig)G4 and abundant infiltration of IgG4-positive plasmacyte and storiform fibrosis in the enlarged organs. It includes Mikulicz's disease (IgG4-related dacryoadenitis and sialadenitis), autoimmune pancreatitis type I, and so on. In Japan, we have been able to measure the IgG4 levels in our clinic since 2010, and we knew that various diseases except IgG4-related disease, also presented with elevated levels of serum IgG4. Eosinopihic disorders, such as Chrug-Strauss syndrome, a part of rheumatoid arthritis and systemic sclerosis can present with high levels of serum IgG4. So the confusion is seen in some clinicians, but we have to recognize that only serological findings cannot lead to the correct diagnosis in IgG4-related disease. The pathological and image findings also are needed. With regard of the treatments for IgG4-related disease, the levels of serum IgG4 often reflected with the therapeutic response, and were also the markers, which predicted the relapse. We describe herein the significance of measuring serum IgG4 levels in the diagnosis and during the treatment for IgG4-related disease.     

Serum IgG levels and complement activity in hypogammaglobulinaemic patients under substitution therapy

Haemolytic activity of the classical and alternative pathways of complement as well as serum levels of C1q, Factor B, Factor H, C3, C4, C3d,g and IgG were determined in 15 hypogammaglobulinaemic patients on immunoglobulin replacement therapy. Alternative pathway activity (AP) and C1q were defective in the presence of low IgG levels and normalized on achievement of normal IgG levels; for both variables the correlation with serum IgG was highly significant. Classical pathway activity (CP), C3, C4 and Factor H serum levels were normal independently of IgG levels; Factor B and C3d, g serum levels were elevated in hypogammaglobulinaemic patients regardless of IgG levels. The present report supports the hypothesis that IgG serum levels influence complement function.     

Individual patient variations in the kinetics of intravenous immune globulin administration

Subjects with primary immunodeficiency received modified immune serum globulin (IGIV) intravenously at various dose levels in long-term therapeutic studies. Therapy was effective and essentially free from adverse reactions. Two pertinent observations were made relating to the attained levels of serum IgG. Over a dose range of 100-225 mg/kg, the serum IgG level directly reflects the dosage administered. Sequential analysis of serum levels of IgG demonstrated three patient populations in 14 subjects receiving 150 mg/kg. The largest group, nine patients, had progressive reduction of serum IgG values compatible with the half-life of the reagent, with a return to the original serum IgG level in four weeks. A second population of four patients had a slower reduction of serum IgG over the four-week period. IgG values were significantly elevated over baseline values at the time of the next due infusion. In one subject serum IgG values varied greatly with rapid drops and elevations unrelated to the infusion.     

Low immunoglobulin E flags two distinct types of immune dysregulation

During the last two decades, hyper‐immunoglobulin (Ig)E syndromes have been characterized clinically and molecularly in patients with genetically determined primary immunodeficiencies. However, the detection of low IgE levels, defined here as below detection limit in the routine clinical immunology laboratory, has received little attention. We analysed the association of serum IgA, IgM and IgG levels (including IgG subclasses) with low, normal or high serum IgE levels in patients evaluated in a single‐centre out‐patient immunodeficiency and allergy clinic. The correlation of serum IgE levels with IgG subclasses depended on the clinical phenotype. In patients with immunodeficiencies, IgE correlated with IgG2 and IgG4 but not with IgG3. In contrast, in patients referred for signs of allergy, IgE correlated with IgG3 but not with IgG2. A low IgE result was associated with low IgG3 and IgG4 in allergy referrals, while immunodeficiency referrals with a low IgE result had significantly lower IgG1, IgG2 and IgG4 levels. Hierarchical clustering of non‐IgE immunoglobulin profiles (IgM, IgA, IgG, IgG1–4) validated that non‐IgE immunoglobulin levels predict the clinic referral, i.e. phenotype, of low‐IgE patients. These results suggesto guide the clinical management of patients with low serum IgE levels.     

Hyper-response of serum IgG1 to Staphylococcus aureus peptidoglycan in patients with hyper-IgE syndrome.

The hyper-IgE (HIE) syndrome is characterized by high IgE serum levels, chronic dermatitis and recurrent infections. To determine whether an impairment of the antibody response to Staphylococcus aureus contributes to infections in this syndrome we measured total serum IgG subclass, specific IgG1 and IgG2 levels against peptidoglycan (PG), the immunodominant cell wall component of S. aureus and serum opsonic activity to PG. Of the 14 patients with HIE syndrome, nine had increased level of serum IgG1 and six had IgG2 subclass deficiency. In regard to specific response of IgG1 and IgG2 antibodies to PG, patients were divided into five groups related to ages and compared with 10 control subjects for each age cohort. Patients with HIE syndrome had significant high levels of serum-specific IgG1 to PG and significant decreased levels of serum-specific IgG2 to PG in all five groups. Additionally, serum opsonic activity in patients was significantly higher than that in normal control subjects. It is concluded that IgG2 deficiency or poor IgG2 antibody response to S. aureus is not the explanation of the abnormal susceptibility to S. aureus infections of HIE patients.     

Glomerular and serum immunoglobulin G subclasses in IgA nephropathy

The distribution of human IgG subclasses among mesangial glomerular deposits of 11 patients with IgA nephropathy (IgA-N) was examined by indirect immunofluorescence with subclass-specific mouse monoclonal antibodies (mAb). A subclass restriction was observed with mesangial deposits containing almost exclusively IgG1 (81% of the studied biopsies) and IgG3 (64%). IgG2 was present in only 1 out of the 11 cases studied and IgG4 was never found to be present, although seven different anti-IgG4 mAb were used. In addition, serum levels of total IgA and IgG, as well as serum IgG subclass levels, were measured in 27 patients with IgA nephropathy by an indirect competitive immunoenzymatic assay using mAb. It was noted in IgA-N patients, but not in normal individuals, that there was significant positive correlation between total IgA and IgG serum levels which was entirely due to a positive correlation between total serum IgA and IgG2 levels. This study provides no explanation for the subclass restrictions observed but suggests that (i) the presence of IgA-IgG1-IgG3 in mesangial deposits may be secondary to an antigenic stimulation, possibly viral, and (ii) the positive correlation between IgA and IgG2 serum levels may result from an increased T helper function.     

B lymphocyte stimulator protein-associated increase in circulating autoantibody levels may require CD4+ T cells: lessons from HIV-infected patients

To assess the helper T cell dependence of B lymphocyte stimulator (BLyS) protein-driven autoantibody production in vivo, serum levels of BLyS protein, total IgG, and anti-IgG anti-phospholipid (aPhL) autoantibodies from HIV-infected patients (n = 105) with varying degrees of CD4+ cell depletion and healthy control donors at low risk for HIV (n = 64) were determined. Peripheral blood mononuclear cells from these subjects were stained for surface expression of BLyS protein. Monocyte surface expression and serum levels of BLyS protein were increased in HIV-infected patients as were serum total IgG and IgG aPhL autoantibody levels. No associations were detected between increased serum BLyS protein levels and patient age, sex, disease duration, history of opportunistic infection or malignancy, or serum total IgG levels. However, serum levels of IgG aPhL autoantibodies were greater in patients with high serum BLyS protein levels than in those with normal serum BLyS protein levels. Importantly, this association between serum levels of BLyS protein and IgG aPhL was appreciated only in patients who were not severely CD4+ cell-depleted and not in patients who were severely CD4+ cell-depleted (peripheral blood CD4+ cell counts 相似文献   

Herpes simplex-specific IgG subclass response in herpetic keratitis

The measurement of the local IgG response in ocular Herpes simplex virus infection presents particular problems due to the difficulty in obtaining sufficient tear samples and the possible transudation of IgG from the serum to the inflamed eye. Using specific monoclonal antibodies to Human IgG subclasses in an enzyme-linked immunoabsorbant assay (ELISA) the local IgG antibody response in Herpes simplex keratitis was analysed. All serum samples from patients and controls contained quantifiable levels of HSV specific IgG1 and IgG4 antibody. Comparison of serum antibody levels with tear levels for patients showed that HSV specific IgG1 serum concentrations were 16.1 fold or more higher than in tears, whereas IgG4 concentrations were only 6.5 fold higher in serum than in tears. This difference was not apparent in the control group. Radioimmunoprecipitation assay of 35S-methionine labelled HSV antigens revealed only minor differences in the protein profiles produced by immunoprecipitation using serum or tear antibody. These results suggest a role for IgG4 antibodies in mucosal immunity in the eye as has been suggested for the mucosal surface of the lung.     

Comparative studies on the levels of serum IgG1 and IgG2a in susceptible B10.BR mice infected with different strains of the intestinal nematode parasite Trichuris muris

Comparative studies were carried out on the levels of serum IgG1 and IgG2a in susceptible B10.BR mice infected with different strains of Trichuris muris (E-J and S strains). As infection proceeded, levels of IgG1 and IgG2a increased in mice infected with either strain until at least day 32 post-infection (p.i.). There were no differences in the IgG1 levels on days 14, 20, and 25 p.i. between mice infected with either E-J or S strain, whereas IgG2a levels on days 20, 25, and 32 p.i. were higher in S-infected mice than those in E-J-infected mice. Isotype switching to IgG2a is entirely dependent on interferon gamma (IFN-gamma) and, according to our previous results, the period of high IFN-gamma production in S-infected B10.BR mice is long compared to E-J-infected B10.BR mice. Thus, increased levels of IFN-gamma may sustain high levels of serum IgG2a in S-infected mice. Taken together, levels of serum IgG2a are useful markers of IFN-gamma production in T. muris infection.     

Positive direct antiglobulin test and high serum immunoglobulin G values

To investigate the association between the positive direct antiglobulin test (DAT) and hypergammaglobulinemia, the authors prospectively studied 154 patients, classified into three groups: Group 1, 52 patients with a positive DAT result in pretransfusion samples; Group 2, 52 patients with a negative DAT result; and Group 3, 50 patients initially found to have an elevated serum immunoglobulin G (IgG) level. Serum protein electrophoreses and IgG quantifications were performed for all three groups. Serum haptoglobin and lactate dehydrogenase (LD) isoenzyme electrophoreses were also assayed for Group 1. Of 52 patients in Group 1, 17 (33%) had an elevated serum IgG level and nonreactive eluates. Clinical history, haptoglobin, and LD isoenzyme studies did not suggest increased red blood cell destruction. Only 2 (4%) of 52 patients in Group 2 had an elevated serum IgG level. Of 50 in Group 3, 25 (50%) had a positive DAT result with nonreactive eluates and did not have hemolytic diseases. Two of 10 patients (20%) with serum IgG levels ranging from 18 to 20 g/L (1.8-2.0 g/dL), 13 of 29 (45%) with serum IgG levels from 20 to 40 g/L (2.0-4.0 g/dL), 4 of 6 (67%) with serum IgG levels from 40 to 60 g/L (4.0-6.0 g/dL), and 6 of 6 (100%) with serum IgG levels from 60 to 80 g/L (6.0-8.0 g/dL) had a positive DAT result. The authors concluded there is a significant correlation between a positive DAT result and serum IgG concentrations and that the higher the elevated serum IgG, the more frequently the positive DAT result is observed. Elevated serum IgG levels may explain many positive DAT results in pretransfusion blood samples.     

Low immunoglobulin G level is associated with poor outcomes in patients with sepsis and septic shock

BackgroundDespite studies on low immunoglobulin G (IgG) levels in critically ill patients, their association with clinical outcomes in sepsis patients remains disputed. Herein, we determined the association between low IgG levels and clinical outcomes and investigated the 28-day mortality in patients with low IgG levels.MethodsWe retrospectively identified 238 patients whose serum IgG levels were measured upon intensive care unit admission using medical record data collected between January 2013 and August 2018. We extracted data on patient characteristics, severity scores (APACHE II, SOFA score), neutrophil-lymphocyte ratio (NLR), procalcitonin levels, and serum IgG levels and calculated the cut-off value for the IgG level according to the evaluated clinical outcomes. The primary outcome was 28-day mortality.ResultsThere were no significant differences in NLR and procalcitonin levels between survivors and non-survivors; serum IgG levels were significantly higher in survivors than in non-survivors (P = 0.004). A serum IgG cut-off value of 670 mg/dL was calculated from receiver operating characteristic curve analysis, and serum IgG levels significantly predicted survival with an area under the curve of 0.63 (95% CI, 0.54–0.72) (P = 0.004). Patients with low IgG levels (<670 mg/dL) had significantly higher mortality rates than those with normal IgG levels (≥670 mg/dL) (P < 0.001).ConclusionOur results reveal that low IgG levels (<670 mg/dL) in critically ill patients are associated with poor clinical outcomes related to 28-day mortality. In patients with sepsis, low IgG levels could be a predictor of poor outcome.     

Graves病中IgG亚型水平的变化

目的 Graves病(Graves′ disease, GD)作为一种自身免疫性甲状腺疾病,其发生存在免疫调节因素的参与,目前对IgG亚类在自身免疫性甲状腺疾病(autoimmune thyroid disease, AITD)中的研究主要集中于针对血清中特定自身抗原的IgG亚型的研究,并无血清整体IgG亚型变化的相关性研究.本研究观察GD患者血清整体IgG亚型水平的变化,并对于IgG亚型与甲状腺自身抗体变化的相关性进行分析,期望通过该研究进一步了解自身抗体介导AITD的机制.方法 随机收集哈尔滨医科大学附属第二医院就诊的初发GD(n=14)作为观察组,观察对象均为女性,排除其他可能影响甲状腺功能和机体免疫状态的因素.随机选取年龄、性别与观察组相匹配非甲状腺疾病健康者15例作为对照组.于清晨空腹采集患者血清,测定甲状腺功能、甲状腺自身抗体、IgG各亚型.结果 GD组血清中IgG1水平较对照组升高(P<0.05);IgG2 水平也较对照组升高,但与对照组相比差异无统计学意义(P>0.05);IgG3和IgG4水平下降明显(P<0.01).GD亚组血清IgG亚型与甲状腺自身抗体、甲状腺功能相关性分析显示各指标间无相关性(P>0.05).结论 Graves病中存在IgG亚型水平的变化.     

Elevated levels of IgG and IgG4 to Malassezia allergens in atopic eczema patients with IgE reactivity to Malassezia

BACKGROUND: The opportunistic yeast Malassezia is considered to be one of the factors that can contribute to atopic eczema (AE). Elevated serum IgE levels, T-cell proliferation and positive skin prick test (SPT) and atopy patch test (APT) reactions to Malassezia are found among AE patients. METHODS: Sera from 127 AE patients, 14 patients with seborrheic dermatitis (SD) and 33 healthy controls were investigated for IgE and IgG4 to M. sympodialis extract and four recombinant Malassezia allergens; rMala s 1, rMala s 5, rMala s 6, and rMala s 9. In addition, IgG to the recombinant allergens was analyzed. The IgG and IgG4 levels were compared to IgE levels and in vivo reactions (SPT and APT) to Malassezia. RESULTS: AE patients with serum IgE levels >0.35 kU/l to M. sympodialis extract had significantly higher IgG4 levels to M. sympodialis extract than AE patients without detectable serum IgE to M. sympodialis extract, SD patients and healthy controls. Among the AE patients with and without detectable serum IgE to M. sympodialis extract, respectively, there were no differences in IgG4 levels between patients with positive or negative in vivo reactions to M. sympodialis extract. IgG4 to the rMala s allergens was almost exclusively found among patients with IgE to the same allergen. Within the four tested rMala s allergens, most IgG4 reactions were found to rMala s 6, an allergen with homology to cyclophilin. CONCLUSIONS: Elevated serum IgG4 to M. sympodialis extract accompanies elevated serum IgE to the extract. This is further confirmed by the association between IgG/IgG4 and IgE to recombinant Malassezia allergens.     

High anti-IgE levels at birth are associated with a reduced allergy prevalence in infants at risk: a prospective study

Development of atopic disease was prospectively studied in 148 children from birth to the age of 18 months and related to serum levels of IgG anti-IgE antibody. Children with a dual heredity of allergy, but remaining healthy, had significantly higher IgG anti-IgE levels at birth than children with a similar predisposition to allergy, who became allergic. Children with increased allergy risk, defined by elevated IgE levels at birth (>= 0.53 kU/l) and with probable allergy symptoms had also significantly higher IgG anti-IgE levels at birth than children of the same risk group, developing definite allergy. Independent of allergy risk, there was a significantly lower prevalence of atopic disease in children with cord serum levels of IgG anti-IgE above 350AU.1 than in children with lower levels. Additionally, we showed that the allergy predictive capacity of IgE levels in cord serum was slightly improved in specificity, sensitivity and efficiency by including not only the family history of allergy, but also cord serum levels of IgG anti-IgE. Our results thus raise the possibility that high levels of IgG anti-IgE protect children of increased allergy risk from early development of atopic disease and reduce the severity of symptoms.     

Immunoglobulins, cognitive status and duration of illness in alzheimer's disease

Immunologic changes have been reported in the dementing illnesses of mid and late life. The results of two studies of drug-free males meeting research diagnostic criteria for primary neuronal degeneration of the Alzheimer's type suggest that serum IgG levels decrease with the progression of dementia. Serum IgG levels were inversely correlated with duration of illness and the levels of psychiatric symptomatology. Performance on the mini-mental status examination was positively associated with serum IgG concentrations.     

Serum levels of immunoglobulins (IgG, IgA, IgM) in a general adult population and their relationship with alcohol consumption, smoking and common metabolic abnormalities

The present study investigated serum immunoglobulin (Ig) concentrations in relation to demographic factors, common habits (alcohol consumption and smoking) and metabolic abnormalities in an adult population-based survey including 460 individuals. Serum levels of interleukin (IL)-6, a marker of inflammation, were also determined. After adjusting for confounders, male sex was associated positively with IgA levels and negatively with IgM levels. Age was associated positively with IgA and IgG levels. Smoking was associated negatively with IgG levels. Heavy drinking was associated positively with IgA levels. Metabolic abnormalities (obesity and metabolic syndrome) were associated positively with IgA levels. Abdominal obesity and hypertriglyceridaemia were the components of metabolic syndrome associated most strongly with serum IgA. Heavy drinkers with metabolic syndrome showed particularly high serum IgA levels. Serum IL-6 levels were correlated positively with IgA and IgG concentrations. It is concluded that sex, age, alcohol consumption, smoking and common metabolic abnormalities should be taken into account when interpreting serum levels of IgA, IgG and IgM.     

Serial changes in the galactosylation of autoantibodies and serum IgG in autoimmune haemolytic anaemia

A number of systemic autoimmune diseases are associated with increased levels of the agalactosyl (G0) IgG isoforms that lack a terminal galactose from the C(H)2 domain oligosaccharide. The aims were to determine whether there are also persistently high levels of G0 autoantibodies or serum IgG in autoimmune haemolytic anaemia (AIHA), and whether any changes in galactosylation over time are related to the course of disease. Autoantibodies eluted from red blood cells, and serum IgG, were obtained from a patient with chronic AIHA over a 21 month period, and the degree of galactosylation measured using a lectin-binding assay. There were wide fluctuations in the galactosylation of autoantibody and serum IgG, but these changes were unrelated to the severity of the anaemia. The galactosylation of autoantibody and serum IgG varied independently, and the autoantibodies were preferentially G0 in comparison with serum IgG in only half of the serial samples. We conclude that AIHA differs from other, systemic autoimmune conditions in that high levels of G0 autoantibodies or serum IgG are not persistent, and that changes in galactosylation do not parallel the course of disease.     

Experimental hypersensitivity pneumonitis: serum immunoglobulins G1, G2, M, A and E in Micropolysopra faeni sensitized and desensitized calves

Weekly evaluation of serum antibody activity in IgA, IgM, IgG1 and IgG2 as well as serum IgE levels indicates highly significant reduction in IgE and elevation of IgA in calves experimentally desensitized with Micropolyspora faeni soluble antigen. Serum IgG2, IgG1 and IgM levels were also elevated. Results are discussed in the light of the possible significance of reagin-mediated reactions in initiation of hypersensitivity pneumonitis.     

Evaluation of inflammatory and renal-injury markers in women treated with antibiotics for acute pyelonephritis caused by Escherichia coli

The evolution and the relationship between inflammatory and renal-injury markers in women with acute uncomplicated pyelonephritis under antimicrobial therapy were investigated in a prospective study. Markers were measured before and 6 and 24 h after the intravenous administration of 1 g of ceftriaxone. Before treatment, the median levels of all markers except the serum creatinine levels were high. Twenty-four hours after the onset of antibiotic treatment, the C-reactive protein (CRP) level continued to be high, while the serum interleukin-6 (IL-6) levels and the urine IL-6, IL-8, albumin, and immunoglobulin G (IgG) levels decreased significantly. In contrast, serum creatinine and tumor necrosis factor alpha levels and urine N-acetyl-beta-glucosaminidase, alpha1-microglobulin, and beta2-microglobulin levels did not change over time. There was a significant correlation between IL-6 and IL-8 levels and urine albumin and IgG levels (urine albumin and IgG levels are glomerular and urinary tract-injury markers) as well as between serum CRP levels and the levels of the tubular-injury markers. In women with acute pyelonephritis, appropriate antibiotic treatment rapidly decreases serum IL-6 levels and urine IL-6 and IL-8 levels, which correlate well with urine albumin and IgG levels.