IL-10 controls Aspergillus fumigatus- and Pseudomonas aeruginosa-specific T-cell response in cystic fibrosis

Up to 90% of patients with cystic fibrosis (CF) are chronically colonized with Pseudomonas aeruginosa, and 10% to 50% of CF patients are colonized with Aspergillus fumigatus. Despite an extensive inflammatory reaction, patients cannot eliminate the microorganisms. The present study demonstrates that an IL-10 mediated T-cell tolerance to major infectious agents A. fumigatus and P. aeruginosa plays an important role in the control of T-cell-mediated inflammatory responses in CF. Peripheral blood mononuclear cells of CF patients secreted significantly higher amounts of IL-10. T-cell response against recombinant A. fumigatus antigens rAsp f 3, rAsp f 4, rAsp f 6, and heat-inactivated P. aeruginosa was controlled by IL-10. Proliferation and interferon-gamma production was significantly increased when endogenous IL-10 was blocked in aspergillus and pseudomonas antigen-stimulated cells of CF patients. The role of IL-10 was further documented by increased spontaneous proliferation of peripheral blood mononuclear cells of CF patients after preincubation with antisense oligonucleotides blocking the synthesis of IL-10 receptor-associated kinases janus tyrosine kinase 1 and tyrosine kinase 2. Together, these data demonstrate an important role of IL-10-mediated peripheral T-cell tolerance to P. aeruginosa and A. fumigatus in the control of the intensity of the inflammatory T-cell response in CF.     

Selective enhancement of human IgE production in vitro by synergy of pokeweed mitogen and mercuric chloride

Selective stimulation of IgE production by pokeweed mitogen (PWM) plus mercuric chloride (HgCl₂) was further investigated in peripheral blood mononuclear cells (MNC) from non-atopic donors, who are high and low responders to PWM stimulation with respect to IgG, IgM and IgA production, and from various patients with elevated serum IgE levels. Non-atopic high responders showed a strong selective increase in IgE plaque forming cells (PFC) without changes in IgG, IgM and IgA PFC, whereas low responders showed a slight increase in IgE PFC only when B cells were co-cultured with mitomycin C (MMC)-treated T cells. In patients with elevated serum IgE levels, PWM plus HgCl₂ caused a variable selective increase in IgE PFC, however, there was no correlation between IgE PFC production and serum IgE levels.     

滤泡辅助性T细胞及半乳糖缺乏的IgA1在儿童过敏性紫癜中的表达及意义

目的 探讨滤泡辅助性T（Tfh）细胞和半乳糖缺乏的IgA1（Gd-IgA1）在儿童过敏性紫癜（HSP）发病机制中的作用及两者之间的相关性。方法 选取初发HSP患儿36例,根据是否发生紫癜性肾炎（HSPN）分为HSPN组（11例）和非HSPN组（25例）。另选取15例门诊体检儿童作为健康对照组。采用流式细胞术检测外周血中Tfh细胞（CD4⁺CXCR5⁺ICOS⁺）比例。采用ELISA法检测外周血中IL-21、IL-6、血清IgA1、血清Gd-IgA1表达水平。采用Pearson相关分析法分析HSP组患儿血清Gd-IgA1浓度与Tfh细胞比例及其相关因子的相关性。结果 HSPN和非HSPN组患儿外周血Tfh细胞比例及IL-21、IL-6表达水平较健康对照组升高（P < 0.05）,HSPN组上述指标较非HSPN组亦明显上升（P < 0.05）。HSPN和非HSPN组患儿血清中IgA1、Gd-IgA1表达水平较健康对照组升高（P < 0.05）,HSPN组患儿血清IgA1和Gd-IgA1水平较非HSPN组亦明显升高（P < 0.05）。HSP组患儿血清Gd-IgA1水平与Tfh细胞比例及IL-21、IL-6水平均呈显著正相关关系（P < 0.05）。结论 Tfh细胞及其相关细胞因子和血清Gd-IgA1共同参与HSP/HSPN的发生。Tfh细胞可能介导了Gd-IgA1生成增加。     

Interferon-gamma and interleukin-10 production among HIV-1-infected and uninfected infants of HIV-1-infected mothers

Immunologic consequences of exposure to HIV-1 in utero are still poorly understood. This study investigates relationships between type-1 [interferon-gamma (IFN-gamma)] and type-2 (IL-10) cytokine production and maternal-infant HIV-1 transmission. Cord blood leukocytes from deliveries of 71 HIV-1-infected and 11 uninfected mothers were tested for in vitro IFN-gamma and IL-10 production after phytohemagglutinin (PHA) stimulation. The infants of these HIV-1-infected mothers were followed prospectively after birth to determine HIV vertical transmission, and IFN-gamma and IL-10 production was measured again at 6 mo. Median PHA-stimulated IFN-gamma production was 210 pg/mL in cord blood cells from infected and 73 pg/mL from uninfected mothers (p = 0.12), and median PHA-stimulated IL-10 production was 491 pg/mL in cord blood cells from infected and 161 pg/mL from uninfected mothers (p = 0.004). PHA-stimulated IFN-gamma and IL-10 production alone were not significantly associated with transmission, but relationships between the two cytokines differed among infected and uninfected infants of HIV-1-infected mothers. PHA-stimulated IFN-gamma and IL-10 production was positively correlated among infected (r = 0.7, p = 0.12 in cord blood and r = 0.66, p = 0.03 at 6 mo) but not uninfected infants, and stronger relative production of IFN-gamma to IL-10 was observed among exposed uninfected than among infected infants (p = 0.04). Exposure in utero to HIV-1 may augment production of IL-10 detectable in fetal cord blood. Stronger relative production of IFN-gamma to IL-10 in cord blood cells from infants of HIV-1-infected mothers may be associated with protection against perinatal HIV infection.     

Immunologic and biochemical factors of coincident celiac disease and type 1 diabetes mellitus in children

The objective of the study was to investigate whether immunologic and biochemical events occurring in the course of type 1 diabetes mellitus might play a role in the development of the celiac disease. The study was carried out on 223 children with long-standing diabetes mellitus type 1 (DM1). All the patients had TSH, fT4, fT3, urinary albumin secretion rate, IgA, level of antigliadin antibodies (AGA) IgA and IgG, antitissue transglutaminase IgA antibodies, antiendomysium (EmA) IgA and IgG antibodies and antitireoglobulin antibodies, antithyroid peroxidase antibodies evaluated. Serum TNF-alpha, IL-6, and IL-10 levels were also measured. The group of children with coincident DM1 and celiac disease and without autoimmune thyroiditis was characterized by significantly higher glycosylated hemoglobin, higher serum TNF-alpha, IL-6 but lower serum IL-10 in relation to the remaining diabetic patients. A statistically significant positive correlation was observed between IgA-anti-tTG and serum TNF-alpha (R = 0.28, p = 0.026); between IgG AGA and serum IL-6 (R = 0.31, p = 0.023); and between glycosylated hemoglobin and IgA-anti-tTG (R = 0.21, p = 0.001) and IgA antiendomysium (R = 0.22, p = 0.001). Poor metabolic control, persistent elevated levels of proinflammatory cytokines, and decreased level of antiinflammatory cytokines occurring in the course of type 1 diabetes mellitus might influence the incidence of celiac disease.     

Specific decrease of anti-pseudomonal IgA after anti-pseudomonal therapy in cystic fibrosis

In patients with cystic fibrosis (CF) and chronic colonisation withPseudomonas aeruginosa, specific anti-pseudomonal IgG and IgA, as well as serum immunoreactive protein C, WBC and differential count, ESR, pulmonary function and chest radiograph score were determined before and after a 2 week intravenous course of anti-pseudomonal antibiotics in 32 cases of acute exacerbation of pulmonary infection. Specific anti-pseudomonal IgA but not specific anti-pseudomonal IgG decreased significantly after treatment. Log of anti-pseudomonal IgA but not log anti-pseudomonal IgG correlated well with disease severity as assessed by the Brasfield chest radiograph score (r 0.57), forced expiratory volume in 1 s (r 0.6) as well as C-reactive protein (r 0.62).     

Immunological studies in cystic fibrosis

Evidence is presented to support the concept that much of the allergy in cystic fibrosis (CF) is IgE mediated. Total IgE levels were higher in allergic than in nonallergic CF patients. Levels were also higher in those patients who had had the greatest number of chest infections in the preceding 12 months. IgE antibody levels to Dermatophagoides pteronyssinus, Timothy grass pollen, and Aspergillus fumigatus were higher in those with positive results from skin tests to these allergens. The serum IgG, IgM, and IgA levels of allergic and nonallergic CF patients did not differ but the overall mean values for IgG and IgM were higher than those reported for healthy British children. The highest levels tended to be present in patients with the greatest number of recent major chest infections and the difference was significant for IgG. 16 patients had IgA levels 72SD below the reported means for age-matched controls and 11 of these were nonallergic. IgA levels were also higher in patients who had recently experienced major chest infections. 45 of the patients were tissue types for HLA A and B antigens but no significant clinical associations with single antigens were observed. The antigen phenotype A1 + B8 was more common in datients with multiple allergic symptoms than in those with a single allergy or merely a positive result from a skin test Nonsignificant increases of W19 in patients with frequent infections and of A2 in patients presenting with meconium ileus were also noted. The data presented do not permit a choice to be made between the alternative concepts of allergy as a primary abnormality in CF, and allergy arising secondary to infection.     

Immunoglobulin subclasses and HLA alleles in immunoglobulin A deficiency

Objective : The term “IgA Deficiency (IgAD)” should be reserved for the individuals who do not have detectable disorders known to be associated with low IgA levels. IgG subclass deficiency or a lack of the IgG2 subclass that is specific against polysaccharide antigens, can be seen in many cases.Methods : Forty-five patients (27 males and 18 females; mean age 8.6 years, range 6.3 to 12.8 years) with IgA deficiency who had been admitted to the Department of Pediatric Immunology in Uludag University School of Medicine, Turkey, were included in this study. Serum immunoglobulin (Ig) class and IgG subclass levels, and HLA haplotypes were prospectively determined in patients and healthy controls.Results : Of the 45 patients with IgAD, 1 was found to have a low level of IgG in the serum. Serum Ig levels were also examined in the families of 22 patients. Five patients had low-normal levels of IgM, whilst one had low levels of IgA and IgG. The levels of IgG sublasses were assessed in 23 patients. One patient had a low level of IgG1 ; 2 had low levels of both IgG2 and IgG3, and 11 had low levels of IgG3. IgG subclass concentrations were found to be normal in control groups. HLA alleles were tested in 25 patients. An increased prevelence of HLA-A1, -B8, -B14, -DR1, -DR3, and -DR7 were previously observed in patients with Ig A deficiency. In this study, HLA-A1 allel was found in 3 patients (12 %), HLA-B14 in 3 patients (12%), HLA-DR1 in 10 patients (40 %), HLA-DR7 in 4 patients (16 %) and HLA-DR3 in 1 patient (4 %). HLA-B8 allel was not found in any patient. Twenty-five children with normal IgA levels have chosen as a control group. They had HLA-DR1 (36%), HLA-DR7 (16 %), HLA-B8 (8%), HLA-DR3 (16%). HLA-A1 was not found in any member of our control group.Conclusion : No statistically significant difference in HLA susceptibility alleles was found between patients and healthy controls. Our data suggest that there may be heterogenous HLA distribution patterns in IgA deficiency, or that HLA allel-associated tendency to IgA deficiency may be polygenic.     

新生儿肺炎白细胞介素-10、-13与免疫球蛋白的关系

目的　探讨新生儿肺炎白细胞介素 (IL) 10、 13与免疫球蛋白 (Ig)的关系。 方法　采用免疫酶法(ELISA)和速率散射比浊法检测新生儿肺炎患儿血IL 10、IL 13、IgG、IgA、IgM。以C反应蛋白 (CRP)≥ 2 0mg/L作为诊断细菌感染的界限值 ,结合临床资料 ,将肺炎分为 4组进行结果分析。结果　 1.肺炎组 8型常见病毒及支原体特异性IgM阳性 4 0份 (36 .0 % ) ;对照组 30份血清检测均阴性。病毒及支原体感染 (病毒感染 ) 2 3例(2 0 .7% ) ,细菌感染 4 5例 (4 0 .5 % ) ,混合感染 17例 (15 .3% ) ,不明病原感染 (其他感染 ) 2 6例 (2 3.4 % )。 2 .肺炎组IgA、IgM明显高于对照组 (P <0 .0 5 )。其中病毒感染组IgA明显高于其他感染组和对照组 (P <0 .0 5 ) ;IgM含量为细菌感染组显著高于对照组 (P <0 .0 5 )。 3.病毒感染组IgG、IgA、IgM分别与IL 10有显著相关 (P<0 .0 5 )。混合感染组、细菌感染组和对照组IgM分别与其IL 13呈显著相关 (P <0 .0 5 )。结论　新生儿肺炎时 ,IgA是完成抗病毒体液免疫应答的重要成分 ,IL 10对IgA产生具有调节作用 ;IgM能在抗菌性体液免疫机制中发挥重要作用 ,IL 13有助于调节IgM产生     

急性特发性血小板减少性紫癜患儿免疫功能变化及其临床意义

目的检测特发性血小板减少性紫癜(ITP)患儿的免疫功能并探讨ITP的发病机制。方法抗血小板抗体(PAIgG)测定采用放射免疫法,IgA、IgG、IgM测定采用WL-快速免疫消浊比浊法,T淋巴细胞亚群测定采用APAAP法,血清IL-2、sIL-2R和IL-6测定采用ELISA法。结果 ITP患儿的IL-2、IL-6,IgA、IgM、CD8及IL-2R表达均明显升高(P<0.01),CD4+、CD4+/CD8+细胞均明显减少(P<0.01)。结论细胞免疫及体液免疫异常共同参与ITP致病机制,调节淋巴细胞亚群平衡有助于寻找ITP治疗的新途径。     

Clinical phenotypes associated with selective IgA deficiency: a review of 330 cases and a proposed follow-up protocol

Selective IgA deficiency is the most common Primary Immune Deficiency. Only a small proportion of these patients present during childhood, but this proportion increases over the years, and may be associated with an IgG subclass deficiency with increased susceptibility to respiratory and digestive tract infections. During childhood, IgA deficient patients may also refer to symptoms related to allergic and autoimmune diseases or tumours.AimsTo describe the relationship of selective IgA deficiency with infections, allergic diseases, autoimmune disorders and tumours. To investigate the presence of other immune disorders associated with selective IgA deficiency. To suggest a follow-up protocol for these patients.MethodsRetrospective study of paediatric patients (<18 years) being followed-up in the Clinical Immunology Department between 1992 and 2007, as well as laboratory records with IgA values below 50 mg/L. Clinical records were reviewed (frequency and intensity of diseases associated with selective IgA deficiency) along with immunology tests performed.ResultsA total of 330 paediatric patients were identified with a selective IgA deficiency: 39 (11.8%) suffered from recurrent ear infections (2 developed secondary deafness), 58 (17.5%) from recurrent upper respiratory tract infections, and 20 patients (6%) from recurrent pneumonia, 6 of whom developed secondary bronchiectasis and 2 underwent a lobectomy.A relationship with atopic disease was found in 62 (18.78%) of patients. Regarding digestive disorders, chronic diarrhoea was found in 21 (6.5%), coeliac disease in 22 (6.6%), and persistently high plasma transaminases in 3.Autoimmune manifestations were found in 38 (11.5%), juvenile chronic arthritis, type 1 diabetes, vitiligo, cytopenia, and Crohn's disease, amongst others). Tumours were identified in 5 (1.5%).An IgG sub-class deficiency was found in 5 patients (4%), and 6 patients had a confirmed deficiency in antibody production.ConclusionsIn our cohort, 56.6% of patients with IgA deficiency showed other comorbidities which were, in decreasing frequency: recurrent infections (respiratory and ear infections), allergic diseases, autoimmunity and tumours. Some patients will develop a more severe humoral defect (IgG subclass deficiency with or without antibody deficiency).     

Autoantibodies directed against bactericidal/permeability-increasing protein in patients with cystic fibrosis: association with microbial respiratory tract colonization

BACKGROUND: Cystic fibrosis (CF) is associated with the appearance of serum autoantibodies directed against bactericidal/permeability-increasing protein (BPI). OBJECTIVES: To determine the age-specific seroprevalence rates of anti-BPI-IgG and IgA in a population of patients with CF and to correlate anti-BPI antibody concentrations with microbial respiratory tract colonization and pulmonary function variables at the time of serum sampling and 6 years thereafter. METHODS: Determination of BPI antibodies of the IgG and IgA isotypes using a commercial enzyme-linked immunosorbent assay in sera of a CF serum bank of 1992; correlation of anti-BPI antibody concentrations with age, clinical score, pulmonary function variables in 1992 and 1998, total serum immunoglobulin isotype concentrations and respiratory tract colonization with Pseudomonas aeruginosa and Aspergillus spp. RESULTS: Seventy-one patients (age in 1992, 14.1 +/- 7.5 years) were studied. Reactivities for anti-BPI-IgG and IgA were found in 28 (39%) and 26 (37%) patients, respectively. The seroprevalence of anti-BPI-IgA, but not IgG, increased significantly with age. P. aeruginosa colonization was associated with elevated concentrations of anti-BPI-IgG (P = 0.003) and IgA (P = 0.037). There were significant negative correlations between pulmonary function variables (vital capacity, forced expiratory volume in 1 s) in 1992 and 1998, respectively, and concentrations of anti-BPI-IgG or IgA in a multiple regression analysis. Anti-BPI-IgG, but not IgA, remained significantly associated with P. aeruginosa colonization (P = 0.006) and with reduced vital capacity (P = 0.01) in 1998 after correction for total serum isotype concentration. CONCLUSIONS: Anti-BPI-IgG are strongly associated with concurrent P. aeruginosa colonization and with long term restrictive pulmonary function abnormalities.     

Immune status with empyema thoracis

Objective: To evaluate the humoral and cell mediated immune status of children with empyema thoracis.Methods: Serum IgG, IgA, IgM, Complement C₃ assay and cell mediated immunity (CMI) tests were performed in 33 patients of empyema thoracis, and 14 healthy age matched controls.Results: The mean serum IgG and IgA levels in empyema thoracis and its subgroups were significantly raised as compared to controls. The overall values of IgG and IgA were 104% (P<0.001) and 114% (P<0.01) of normal mean, respectively. The mean serum IgM and complement C₃ levels did not differ significantly in both the groups. The frequency of negative skin reaction to purified protein derivative (PPD) was significantly higher in children with empyema thoracis as compared to controls (P<0.05). The mean absolute lymphocyte count (ALC) was significantly decreased and serum adenosine deaminase (ADA) activity was significantly raised in empyema thoracis in comparison to controls. The overall ALC was 76.1% (P<0.01) and serum ADA activity was 169.4% (P<0.001) of normal mean, respectively. No significant differences were observed in the mean levels of immunoglobulins, complement C₃ and CMI tests between pyothorax and pyopneumothorax and pleural fluid culture positive and negative cases.Conclusions: Thus, both humoral and cell mediated immunity were affected in empyema thoracis patients. However, CMI demonstrated more pronounced change in comparison to humoral immunity     

Role of transforming growth factor-beta in breast milk for initiation of IgA production in newborn infants

BACKGROUND: Transforming growth factor (TGF)-beta has a crucial effect on IgA production, which is the major humoral effector of mucosal immunity. Breast milk contains the abundant amount of TGF-beta in the early period of lactation. AIM-STUDY DESIGN: To verify the notion that TGF-beta in breast milk might contribute to the development of IgA production in newborns, we investigated the association of TGF-beta in maternal colostrum with an increase of serum IgA in newborns during the first month of life. SUBJECTS AND METHODS: The concentrations of TGF-beta1 and TGF-beta2, including IL-6 and IL-10, in colostrum samples from 55 healthy mothers were determined by ELISA. The levels of IgA and IgM in serum samples collected from corresponding newborn babies at birth and at 1 month of age were measured by ELISA. RESULTS: TGF-beta1 and TGF-beta2 were detected in substantial quantities in all colostrum samples, but IL-6 and IL-10 were present only in a proportion of samples. An increase of serum IgA in newborn during the first month of life was significantly higher than that of serum IgM (p<0.001). Notably, an increase of serum IgA in newborns during 1 month of life was well correlated with levels of both TGF-beta1 (r=0.38, p=0.005) and TGF-beta2 (r=0.45, p=0.0005) in colostrum, while that of IgM was marginally correlated with colostral TGF-beta2 (r=0.28, p=0.04). The association of increase of serum IgA in newborns with IL-6 and IL-10 in colostrum was not evident. CONCLUSION: Our findings suggest that TGF-beta in colostrum might serve as the starter of IgA production in newborn infants.     

Immunofluorescence Studies of Lung Tissue in Cystic Fibrosis

Previous studies have suggested that immune mechanisms contribute to lung injury in cystic fibrosis (CF); however, there have been no comprehensive studies of immunofluorescent staining patterns in CF lung tissue. We performed immunofluorescence (IF) studies for immunoglobulins, C3, and fibrinogen on autopsy frozen lung tissue from 21 CF patients. Results were compared with lung findings in patients without CF. In CF-derived lung tissue fibrinogen was ubiquitous along the alveolar wall, alveolar space, and interstitium. Free immunoglobulin G (IgG) and IgA coated the alveolar surface segmentally in 14 and 6 cases, respectively. Unequivocal interstitial deposits were infrequent and IgM was present in blood vessels in one patient only. Intra-alveolar and interstitial inflammatory cells demonstrated cytoplasmic IgG, IgA, and IgM, respectively, in 18, 14, and 6 patients. C3 was seen only segmentally along the alveolar wall in two patients and in blood vessels in one. Antinuclear antibody (ANA) staining of interstitial cells for C3 and immunoglobulins was seen in five patients, four of whom had interstitial pneumonitis. Insignificant amounts of alveolar or interstitial fibrinogen and immunoglobulins in inflammatory cells were seen in controls in the absence of lung inflammation. The IF patterns were similar in the inflammatory lesions of CF and control specimens.

The IF patterns observed in CF lung tissue are consistent with nonspecific vascular leakage and chronic inflammation with little evidence of immune complex deposition in the interstitium or blood vessels. This study confirms previous reports of ANA activity in CF patients, although the significance of this finding is unknown.     

Selective IgA deficiency

Of 140 patients referred to the Pediatric Immunology Clinic during of 12-month period with the symptoms of recurrent infections or allergic respiratory illness, 21 (75%) were found to have selective IgA deficiency defined as serum concentration ≤ 5 mg. with normal levels of IgG and IgM. T lymphocyte number was reduced in the patients where as B cells with surface membrane IgA were increased. Autoantibodies and circulatory immune complexes were found more often in IgA-deficient subjects than in controls. Follow-up beyond the age of 9 years showed a spontaneous increase in serum IgA in 6, whereas 15 continued to have IgA deficiency. The latter group of children were characterized by more frequent infections, a higher prevalence of atopic disease, lower T cell count and serum IgG concentration, higher serum IgE level and a higher prevalence of food antibodies and immune complexes. These observations highlight the natural history and immunologic features of selective IgA deficiency.     

肺炎衣原体感染与冠状动脉改变的关系

目的探讨肺炎衣原体(CP)感染是否引起冠状动脉病变及其相互关系。方法对52例1个月～10岁5个月CP感染患儿进行血清CP-IgM、CP-IgG、IL-6和三酰甘油(TG)等检测,行外周血C反应蛋白(CRP)测定,彩色多普勒超声心动图检查冠状动脉病变。观察CP感染及不同水平的IgM、IgG、IL-6、CRP、TG与冠状动脉病变的关系。结果CP-IgG阳性28例,CP-IgM阳性21例,IgM和IgG均阳性3例。CRP增高12例,IL-6增高5例,TG增高9例。不同水平CP-IgM、CP-IgG、IL-6、CRP、TG的52例CP感染患儿彩色多普勒超声心动图检查均未发现有冠状动脉病变。结论小儿CP感染未引起冠状动脉异常改变。     

Altered antibody isotype in cystic fibrosis: impaired natural antibody response to polysaccharide antigens

Patients with cystic fibrosis (CF) have impaired natural (preinfection) IgG2 antibody responses to Pseudomonas aeruginosa lipopolysaccharide. To investigate the basis for this defect, we measured natural IgG and IgG1-4 antibody levels to Haemophilus influenzae type b polyribophosphate (PRP) and tetanus toxoid by enzyme-linked immunosorbent assay in 24 adult CF patients and 20 normal controls. Immunoglobulin heavy- and light-chain allotypes were determined on 146 Caucasian CF patients and 96 controls. The tetanus toxoid-specific IgG response was predominantly IgG1. CF and control subjects had similar IgG and IgG1 antibody levels. The PRP-specific IgG response was predominantly IgG2. In contrast to tetanus toxoid results, CF patients had lower geometric mean level of PRP-specific IgG compared to normal controls (p = 0.0036). ELISA results were confirmed by liquid-phase 3H-PRP-binding assay: CF patients had a geometric mean serum antibody level of 395 versus 922 ng/ml in controls (p = 0.0044). PRP-specific IgG2 levels were also depressed in CF patients (p = 0.03). CF patients had a lower prevalence of the A2m(2) allotype than the local racially matched control sample (p less than 0.025). Other allotype prevalences including G2m(n) and Km(1) were similar. Impaired IgG2 antibody responses to microbial polysaccharide surface antigens in CF patients might predispose them to persistent endobronchial infection and lead to production of nonopsonizing isotype responses. The potential role of A2m(2), coded for in the H chain locus on chromosome 14, is unknown, but could be related to mucosal IgA2 antibody responses.     

STUDIES OF ESCHERICHIA COLI O ANTIGEN SPECIFIC ANTIBODIES IN HUMAN MILK, MATERNAL SERUM AND CORD BLOOD

ABSTRACT. The quantity and class specificity of E. coli O antibodies in human milk, maternal serum and cord blood was determined by the enzyme-linked immunosorbent assay. The predominant Ig-class of these antibodies in milk was IgA. The initially high levels of antibodies decreased 10-fold during the first days, but there seemed to be a fairly constant daily production of IgA antibodies during the first two months of the nursing period. There was no obvious decline in antibody content from morning to night or during a meal. The ratio milk antibody/serum antibody was very high for IgA, suggesting a local production. The ratios for the IgG were all <1, suggesting a restricted transfer from the serum. Ratios around 1 for IgM did not exclude some local production. In umbilical cord serum the amount of IgG E. coli O antibodies was higher than that in maternal serum. Small amounts of IgM and IgA antibodies was also demonstrated in some cases. In milk as well as in serum there were antibodies against a wide variety of E. coli O groups, not only to the actual E. coli strain dominating the mother's gut flora.