IgG subclass deficiency in childhood. Changes in the antigen specific immune response and significance of low IgG4 level

The definition of IgG subclass deficiency and the correlations between low IgG subclass serum concentrations and high incidence of infections in certain patients are still obscure. Therefore 260 children from 6 months to 18 years with severe recurrent infections or a known immunodeficiency were screened for IgG subclass deficiency. Nine patients with severe IgG2 deficiency (Ig2 less than 0.3 g/l) and 35 patients with non-detectable IgG4 in immunoprecipitation were detected. One of these patients had a concomitant IgA deficiency, eight revealed an additional IgA and IgG2 deficiency, two an IgA, IgG2, and IgG3 deficiency, eighteen an IgG2 deficiency and one patient an IgG2 and IgG3 deficiency. The proportion of patients with non-detectable IgG4 in immunoprecipitation was 13.5% and thus in the same order of magnitude as described in the literature for healthy people. Our data show that there is no relation between low IgG4 serum levels and the increased occurrence of severe infections. In all patients investigated with non-detectable IgG4 in immunoprecipitation the gene for the heavy chain gene constant domain C gamma 4 could be detected by Southern blotting. Using a sensitive ELISA method IgG4 could be directly demonstrated in all patients at a serum level of 0.5-29 micrograms/ml. Specific IgG4 antibodies against protein antigens could not be detected in IgG4-deficient patients. Nevertheless total IgG antibodies against diphtheria and tetanus toxoid reached protecting titers. Patients with IgG2 deficiency showed an impaired immune response against polysaccharides from pneumococci and haemophilus influenzae type b.     

IgG2 deficiency in children with human immunodeficiency virus infection

Infection with the human immunodeficiency virus (HIV) induces a polyclonal B-cell activation. Despite elevated serum immunoglobulin levels, a significant deterioration of the antigen specific humoral immune response exists in most cases. We studied the influence of HIV infection on the serum levels of IgG subclasses in children. We investigated 76 children (aged 15 months to 18 years) with HIV-1-infection. Most children (88%) showed elevated serum immunoglobulin levels. IgA (87%) and IgM (74%) were more often above normal levels for age than IgG (60%). IgG subclass serum levels were significantly altered. The increase in total IgG was mainly due to a marked augmentation of the IgG1 fraction. In most cases IgG3 was simultaneously elevated. Ten children (13%) had very low IgG4 levels (<0.03 g/l). Out of 61 patients older than 2 years 8 (13%) had a profound IgG2 deficiency with normal or elevated total IgG. Four of them also had low IgG4 levels (<0.03 g/l). A correlation between IgG2 deficiency and HIV infection according to the Centres for Disease Control classification for acquired immunodeficiency syndrome could not be demonstrated (three patients with symptomatic and five with asymptomatic infection).     

Atopic features in early childhood autism

BACKGROUND: Autism is a developmental disorder of unknown etiology. Sensitivity to dietary and environmental antigens has been considered in its pathogenesis. AIM: To examine immediate hypersensitivity in early childhood autism. METHODS: We investigated 30 autistic children (23 boys, seven girls 2-4 years old) for atopic history, serum IgG, IgA, IgM, IgE levels, and skin prick tests (SPT) with 12 common antigens. RESULTS: Nine/30 autistic children (30%) and 1/39 (2.5%) age-matched neurological controls from the same hospital had a family history suggestive of atopy (p<0.005). No patient in the autism and 28% in control group had symptoms of respiratory allergy (wheezing or asthma) (p<0.005), and 6/30 (20%) autistic vs. 7/39 (17%) control children had history suggesting other allergic disorders (p=ns). Eleven/23 (47.8%) autistic children had at least one positive skin test, similar to age-matched population controls. Serum IgG, IgA, and IgM levels were within age-appropriate limits. Serum IgE was elevated in four patients (13.3%). Specific IgE levels were negative in four cases with multiple SPT positivity. CONCLUSIONS: This study suggests allergic features based on history, skin tests, and serum IgE levels are not frequent in young autistic children despite family history. This discrepancy between predisposition and manifestation might imply immunological factors or environmental conditions.     

Undetectable IgG4 in immunoprecipitation: association with repeated infections in children?

A total of 210 patients with repeated infections were screened for IgG4 deficiency. In 30 patients (14%) IgG4 was undetectable by radial immunodiffusion (<30 mg/l). Of these patients 17 (57%) were less than 2 years of age. Concomitant IgA deficiency (IgA<0.05 g/l) was demonstrated in 11 cases (37%). IgG2 serum levels below the normal range were found in 26 children. IgG4 could be demonstrated at a concentration of 0.5–29 mg/l in all 30 patients using a more sensitive enzymelinked immunosorbent assay technique. Although a highly selected group of patients was investigated, the percentage of individuals without detectable IgG4 by immunodiffusion was in the same range as reported in the literature for healthy control persons. It is thus concluded that IgG4 serum reference levels have to be defined using more sensitive methods and that the observed severe infections are more likely to be connected with low serum IgG2 and/or IgA levels than undetectable IgG4 as measured by immunodiffusion.This work was supported by a grant from the Deutsche Forschungsgemeinschaft BA 872/1-1     

Immunological evaluation of allergic respiratory children with recurrent sinusitis

The objective of this study was to evaluate humoral immunity of allergic respiratory children with chronic/recurrent sinusitis. Twenty-seven allergic respiratory (persistent mild/moderate asthma and persistent allergic rhinitis) children (7-15-year old) with chronic or recurrent sinusitis were evaluated. Patients had symptoms and abnormal computer tomography scan even after two adequate treatments (long-lasting antibiotics, decongestants, and short-term oral corticosteroids). clinical examination, sweat test, total blood cell count, measurement of serum levels of: total and specific IgE, immunoglobulins (G, M, A), IgG subclasses, antibodies to Haemophilus influenza type b (IgG anti-Ps Hib) and pneumococcal serotypes (IgG anti-Ps 1, 3, 5, 6B, 9V, and 14) before and after active immunization (Act-Hib and Pneumo23, Aventis Pasteur SA, Lyon, France), Rubella neutralizing antibody titers and human immunodeficiency virus antibodies. Specific IgE to inhalant allergens higher than class III were observed in 24/27 patients. One patient had IgA plus IgG2 deficiency and other an IgG3 deficiency. Eight and 12 of 27 patients had IgG2 and IgG3 serum levels below 2.5th percentile, respectively. Immunological responses to protein and polysaccharide antigens were normal in all patients. Although our patients have been appropriately treated of their allergic diseases, they persisted with chronic/recurrent sinusitis and 60% of them had a documented osteomeatal complex blockade. In spite of the diagnosis of IgA plus IgG2 deficiency and an isolated IgG3 deficiency, in all patients an adequate response to Ps antigens was observed. Primary and/or secondary humoral immunodeficiency seems not to be the main cause of chronic/recurrent sinusitis in patients with respiratory allergic disease.     

The relationships among immunoglobulin levels,allergic sensitization,and viral respiratory illnesses in early childhood

Possin ME, Morgan S, DaSilva DF, Tisler C, Pappas TE, Roberg KA, Anderson E, Evans MD, Gangnon R, Lemanske RF, Gern JE. The relationships among immunoglobulin levels, allergic sensitization, and viral respiratory illnesses in early childhood.
Pediatr Allergy Immunol 2010: 21: 990–996.
© 2010 John Wiley & Sons A/S IgE plays an essential role in type I allergy, however, there is less information about the relationship between other immunoglobulins (IgA and IgG) and atopic phenotypes in early childhood. We hypothesized that levels of circulating IgA in early childhood would be inversely related to the number of respiratory infections and the risk of becoming sensitized to allergens. Immunoglobulin levels were analyzed (ELISA) in plasma samples (IgG, IgA), and in nasal secretions (IgA) from children participating in a high‐risk birth cohort study. Samples were available from 264 children at age 2 yr and 257 children at age 4 yr, and results were compared to rates of respiratory illnesses, allergic sensitization, atopic dermatitis (AD), and asthma. Children who were sensitized to allergens had higher rather than lower levels of circulating IgA. A subgroup analysis showed that IgA levels were increased in relationship to foods sensitization (58 vs. 50 mg/dl, p = 0.003) but not aeroallergen sensitization (52 vs. 53 mg/dl, p = 0.11). IgA levels in the plasma correlated with levels of IgE levels (r_s =0.19, p = 0.003). Levels of IgE, but not IgG or IgA, were positively correlated with rates of respiratory illnesses, AD, and the risk of developing asthma. Finally, there were no significant relationships between IgA in nasal secretions and infectious outcomes. In conclusion, low‐normal concentrations of plasma IgA are associated with a reduced prevalence of allergic sensitization in infancy. Further, levels of IgA and IgG in plasma within the range of normal, and IgA in nasal secretions, do not appear to influence the risk of subsequent respiratory illnesses. Further studies to define relationships between IgA and allergic sensitization are likely to provide new insights into the pathogenesis of allergic diseases in infancy.     

Detection of IgA and IgG but not IgE antibody to respiratory syncytial virus in nasal washes and sera from infants with wheezing

BACKGROUND AND OBJECTIVE: The capacity of respiratory syncytial virus (RSV) to stimulate an IgE antibody response and enhance the development of atopy and asthma remains controversial. Nasal washes and sera from 40 infants (20 with wheezing, 9 with rhinitis, and 11 without respiratory tract symptoms) were obtained to measure IgE, IgA, and IgG antibody to the immunodominant, F and G, virion proteins from RSV. STUDY DESIGN: Children (aged 6 weeks to 2 years) were enrolled in the emergency department during the mid-winter months and seen at follow-up when they were asymptomatic. All nasal washes were tested for RSV antigen. Determinations of antibody isotypes (IgE, IgA, and IgG) to RSV antigens were done in nasal washes and sera by using an enzyme-linked immunosorbent assay. In a subset of nasal washes, IgE to RSV was also evaluated by using a monoclonal anti-F(c)E antibody-based assay. RESULTS: Fifteen patients with wheezing, two with rhinitis, and one control subject tested positive for RSV antigen at enrollment. Thirteen patients with wheezing were <6 months old, and most (77%) were experiencing their first attack. Among the children with positive test results for RSV antigen, an increase in both nasal wash and serum IgA antibody to RSV-F(a) and G(a) was observed at the follow-up visit. However, there was no evidence for an IgE antibody response to either antigen. CONCLUSION: Both IgA and IgG antibodies to the immunodominant RSV-F(a) and G(a) antigens were readily detected in the nasal washes and sera from patients in this study. We were unable to demonstrate specific IgE antibody to these antigens and conclude that the production of IgE as a manifestation of a T(H)2 lymphocyte response to RSV is unlikely.     

Correlation between serum immunoglobulin A concentrations and allergic manifestations in infants.

We studied the relationship of serum levels of IgA and IgE to allergic manifestations and otitis media in a cohort of 179 Icelandic children, aged 18 to 23 months. Only one of the infants had IgA deficiency (less than 50 micrograms/ml); all the others had IgA levels that were normal for their age. The children were divided into three groups according to their IgA levels (lowest 25%, intermediate 50%, highest 25%) and the clinical findings analyzed accordingly. The cumulative incidence of definite allergic manifestations was 37%. Asthma and otitis media were significantly more common among the infants with low normal IgA levels than among those with intermediate to high IgA levels. There was also a significant association between the severity of allergic manifestations and low IgA levels (p = 0.002). Children with detectable IgE (greater than or equal to 0.23 kilounit/L) had a higher incidence of atopic manifestations than did children in whom IgE was not detectable, but only a weak correlation was found between the occurrence and extent of allergic symptoms and increasing amounts of IgE beyond the 0.23 kilounit/L level. These findings suggest that atopic manifestations in infants may be more dependent on delayed maturation of IgA production than on overproduction of IgE.     

Clinical impact of altered immunoglobulin levels in Henoch–Schönlein purpura

Background:  The aim of the present study was the identification of immunological features, present at the time of diagnosis, that would predict the severity of Henoch–Schönlein purpura and its outcome.
Methods:  A cohort study was carried out in a tertiary pediatric hospital of 69 children with Henoch–Schönlein purpura, in whom serum complement components C3, C4 and IgA, IgM, IgG were repeatedly determined.
Results:  During the acute phase of the disease in 54/69 patients (78.3%) immunological imbalances were observed. In 24/54 cases (44.4%) certain complications involving the kidneys and the gastrointestinal tract were noted as opposed to in 3/15 children (20%) without immunologic abnormalities. In 50/69 children (72.5%), elevated serum IgA was detected and 16 of them (32%) developed renal involvement while only 1/19 children (5.3%) with normal IgA concentration had renal involvement. Considering separately the group of 9/69 children (13%) with increased IgM and those with normal IgM levels (53/69; 76.8%), irrespective of IgA and IgG concentration, we found a comparable percentage of children who had both renal and intestinal involvement without, however, developing severe complications, which were exclusively seen in patients with increased IgA (5/7 children) and reduced IgM levels. Serum C3 fraction was elevated in 26 children (37.7%) and in 73% of cases it was associated with increased serum IgA values.
Conclusion:  Renal involvement was seen in 32% of children with increased IgA values. Most importantly, elevated IgA concentration along with reduced IgM levels was associated with higher prevalence of severe complications.     

CLINICAL AND IMMUNOLOGICAL ASPECTS OF FOOD ALLERGY IN CHILDHOOD I. Estimation of IgG, IgA and IgE Antibodies to Food Antigens in Children with Food Allergy and Atopic Dermatitis

Abstract Sixtynine children with case histories of food intolerance and 30 food tolerant children with atopic dermatitis have been investigated regarding serum IgE levels and IgE-, IgG, and IgA-antibodies to some common foods. Children with food intolerance had significantly higher IgE levels and to a larger extent specific IgE antibodies to the tested allergens. IgE antibodies to cow's milk were found in 71% of the children with histories of cow's milk allergy but occurred also in similar titers in 27% of milk tolerant children with other food allergies. IgE antibodies to egg-white occurred in 88% of egg allergies, but low and moderate titers were also found in 17% of children without food intolerance. However, all children with high titers had symptoms of egg allergy. IgE antibodies to the fish allergen were only found in fish allergic children while IgE antibodies to soy-bean and green peas were found less consistently. The level of serum IgA antibodies to milk was similar in both groups. The IgG antibody titers to all tested food antigens seemed to parallel the IgE antibody titer to the same food. It was not possible to correlate the IgG antibody titers to symptoms.     

Anti-immunoglobulin antibodies in children with Schönlein-Henoch syndrome. Absence of serum anti-IgA antibodies

Circulating immune complexes (CIC) that simultaneously contain IgG and IgA are frequently found in IgA nephropathy (IgA-N) and the Schönlein-Henoch syndrome (SHS). The presence of anti-immunoglobulin antibodies (IgA anti-IgG and IgG anti-IgA) was studied by ELISA in the serum of 39 children with SHS and compared to 30 normal children. The mean level of IgG anti-IgA antibodies (240±104 u/ml) in SHS patients was similar to control values (251±85 u/ml); the IgA anti-IgG antibodies were increased, although only the antibodies against Fc fraction of IgG were elevated (185±71 u/ml in patients vs 127±24 /ml in controls,P<0.0001) without a significant increase of IgA anti-IgGFab antibodies (141±54 /ml vs. 137±25 u/ml); 16/39 (41%) of the patients had increased levels of IgA anti-IgGFc and 6 of these had also high IgA anti-IgGFab. None of these patients had high IgA anti-IgGFab antibodies without simultaneous augmentation of IgA anti-IgGFc. Only 3/39 (7.7%) of SHS patients showed high levels of IgG anti-IgA antibodies. The correlation of IgA anti-IgGFc antibodies with IgA anti-IgGFab was very strong (P<0.0001) but lower with IgG anti-IgA antibodies (P<0.002). In addition, 8/39 children had renal involvement, nevertheless in these patients the findings were quite similar, with a non-significant elevation of IgA anti-IgGF ab antibodies. These results show that the IgA anti-IgG antibodies are more frequently increased than IgG anti-IgA antibodies in the SHS; moreover they are mainly directed against Fc fraction and are IgA-FR isotype. Our findings suggest that the CIC in SHS are likely formed by the reaction of IgA antibodies against IgG and not vice versa.     

Increased serum IL-2R levels in coeliac disease are related to CD4 but not CD8 antigens.

Forty-three coeliac children, ranging from 1 year and 3 months to 14 years and 9 months, were studied. Twenty-eight patients were in an active phase of the disease, and 15 were in remission. The criteria of coeliac disease (CD) activity were established according to the results of IgA anti-endomysial antibodies (IgA-AEm). Interleukin 2 receptor (IL-2R) and CD4 and CD8 antigens were measured in serum samples by an ELISA technique using two noncompetitive monoclonal antibodies. Antigliadin antibodies of IgG (IgG-AGA) and IgA (IgA-AGA) classes were also measured. The AEm-positive coeliac patient group showed values of 1,860 +/- 948 U/ml for IL-2R, 430 +/- 228 U/ml for CD8, and 36.8 +/- 25.1 U/ml for CD4. AEm-negative patients showed values of 980 +/- 436 U/ml, 350 +/- 243 U/ml, and 24.1 +/- 20 U/ml, respectively. IL-2R levels were the only ones significantly elevated (p < 0.005) in the active coeliac group. On the other hand, IgG-AGA and IgA-AGA were both clearly increased (p < 0.001). IL-2R levels in active coeliac patients correlated with CD4 levels (p < 0.05), but not with CD8, IgG-AGA, and IgA-AGA levels. We also found a surprising negative correlation between AEm antibodies of IgA2 class with both IL-2R (r = 0.471; p < 0.05) and CD8 (r = 0.616; p < 0.05). The results show that in CD there is a lymphocyte activation affecting mainly CD4+ cells and not correlated with serum AGA levels, suggesting an independence of both immunological phenomena and probably with different locations of origin.     

Undetectable IgE responses after respiratory syncytial virus infection.

Sequential nasopharyngeal secretions were collected from 81 infants from one day to three months after admission to hospital with respiratory syncytial virus (RSV) infection. Samples from 21 infants were assayed for anti-RSV IgE in an antigen capture ELISA assay. No IgE antibodies were detected although an assay of IgA antibodies carried out in parallel by a similar technique detected IgA antibodies in the secretions of all patients tested. Neither prior absorption of IgA or IgG, concentration of the secretions by freeze drying, nor enzyme amplification of the assay revealed any virus specific IgE. Using an antibody capture ELISA with a sensitivity of 0.85 IU/ml, IgE could be detected in sequential secretions of only one of the 81 RSV infected infants studied. Further testing of the secretions from 12 of these patients and those of a further 15 using an enzyme amplified assay with a sensitivity of 0.1 IU/ml revealed no further positives. Low concentrations of IgE were found in the sera of the majority of infants with RSV infection but they did not differ from those of virus negative children of a similar age collected between RSV epidemics. No rise in mean serum IgE concentrations between acute and convalescent samples was observed. No virus specific IgE was detected in the sera of any infant using the enzyme amplified antigen capture ELISA.     

Clinical and immunological aspects of food allergy in childhood. I. Estimation of IgG, IgA and IgE antibodies to food antigens in children with food allergy and atopic dermatitis

Sixtynine children with case histories of food intolerance and 30 food tolerant children with atopic dermatitis have been investigated regarding serum IgE levels and IgE-, IgG, and IgA-antibodies to some common foods. Children with food intolerance had significantly higher IgE levels and to a larger extent specific IgE antibodies to the tested allergens. IgE antibodies to cow's milk were found in 71% of the children with histories of cow's milk allergy but occurred also in similar titers in 27% of milk tolerant children with other food allergies. IgE antibodies to egg-white occurred in 88% of egg allergies, but low and moderate titers were also found in 17% of children without food intolerance. However, all children with high titers had symptoms of egg allergy. IgE antibodies to the fish allergen were only found in fish allergic children while IgE antibodies to the fish allergen were only found in fish allergic children while IgE antibodies to soy-bean and green peas were found less consistently. The level of serum IgA antibodies to milk was similar in both groups. The IgG antibody titers to all tested food antigens seemed to parallel the IgE antibody titer to the same food. It was not possible to correlate the IgG antibody titers to symptoms.     

SERUM IMMUNOGLOBULIN LEVELS IN THE COURSE OF ANAPHYLACTOID PURPURA IN CHILDREN

Abstract. Serum levels of immunoglobulins (IgG, IgA, IgM, IgD and IgE) were determined at frequent intervals in the course of anaphylactoid purpura (AP) in children. AP was cured without complications in 16 out of 26 cases, recurring in 7 cases. Melena was manifested in 9 cases and nephropathy in 5. The levels of IgA and IgM were elevated in AP, but serum IgG, IgD and IgE showed no significant changes. The serum level of IgM was significantly (p<0.0125) higher in patients with AP nephropathy than in those with recent AP. The elevated serum IgA and IgM levels are possibly related to the pathogenesis of AP and/or its renal involvement.     

Undetectable IgE responses after respiratory syncytial virus infection

Sequential nasopharyngeal secretions were collected from 81 infants from one day to three months after admission to hospital with respiratory syncytial virus (RSV) infection. Samples from 21 infants were assayed for anti-RSV IgE in an antigen capture ELISA assay. No IgE antibodies were detected although an assay of IgA antibodies carried out in parallel by a similar technique detected IgA antibodies in the secretions of all patients tested. Neither prior absorption of IgA or IgG, concentration of the secretions by freeze drying, nor enzyme amplification of the assay revealed any virus specific IgE. Using an antibody capture ELISA with a sensitivity of 0.85 IU/ml, IgE could be detected in sequential secretions of only one of the 81 RSV infected infants studied. Further testing of the secretions from 12 of these patients and those of a further 15 using an enzyme amplified assay with a sensitivity of 0.1 IU/ml revealed no further positives. Low concentrations of IgE were found in the sera of the majority of infants with RSV infection but they did not differ from those of virus negative children of a similar age collected between RSV epidemics. No rise in mean serum IgE concentrations between acute and convalescent samples was observed. No virus specific IgE was detected in the sera of any infant using the enzyme amplified antigen capture ELISA.     

Immunoglobulin E in the sera of infants and children.

The serum IgE level has been studied from birth up to 14 years of age. The mean serum IgE concentration was found to be correlated with age. Parallel measurements in cord blood and maternal blood yielded a mean of 25 I.U./ml (range, 0--90 I.U.) for the former and one of 124 I.U./ml (range, 50-600 I.U.) for the latter. The normal IgE level ranged from 20 to 100 I.U./ml in infants and from 100 to 200 I.U./ml in children, but even values of 400 to 600 I.U. did not necessarily reflect a pathological condition. In the majority of patients with eczema, urticaria and spastic bronchitis, high IgE levels were measured. The highest individual and mean values were obtained in children harbouring intestinal helminths, though a normal IgE level also occurred in such patients. In coeliac disease the values were within normal limits.     

肾病综合征患儿免疫球蛋白检测与应用激素的探讨

目的检测原发性肾病患儿IgG、IgA、IgM、IgE、C3水平,探讨肾病患儿对肾上腺皮质激素(泼尼松)的敏感性,了解肾病的发病机制,指导临床治疗。方法分别采用散射比浊法检测血清IgG、IgA、IgM、C3及ELISA法检测血清IgE。结果原发性肾病患儿与正常对照组比较,血清IgA、C3无显著差异,肾病患儿血清IgG水平明显低于正常儿童,IgM、IgE明显高于正常儿童,单纯型与肾炎型肾病结果一致。单纯型与肾炎型肾病对激素治疗敏感性比较有非常显著性差异(x2=18.48 P< 0.005);原发性肾病患儿血清IgE升高组与IgE不升高组对激素治疗的敏感性比较有非常显著性差异(x2=12.46 P< 0.005)。结论原发性肾病综合征患儿存在免疫球蛋白合成异常,可能与患儿体液免疫紊乱有关。而激素治疗敏感性与肾病综合征临床分型及IgE水平高低有关。     

Clinical Manifestations in Selective IgA Deficiency in Childhood; A Follow-up Report

ABSTRACT. Clinical manifestations in 40 children with selective IgA deficiency were studied during a follow-up period of 2-10 years. The patients were divided into two groups: group I consisted of 25 children with "sporadic" IgA deficiency and group II of 15 children with "familial" IgA deficiency. Respiratory tract infections including otitis media were frequent in both groups. Concomitant IgG,-IgG, deficiency was found in two patients in group I. Longitudinal serum IgG levels were elevated significantly in both groups. Atopic complaints were observed in 10 children of the "sporadic" group, but only in two of the "familial" group. However, elevated serum IgE levels were more often found in group II. Two children of group I were mentally retarded and chromosomal examination showed abnormalities in both. Anti-IgA antibodies were detected in one child in group I and three children in group II. These three patients had an IgA deficient mother with class-specific anti-IgA antibodies. Concomitant IgG₄-IgE deficiency was found in all four.     

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.