Search

Both the innate and adaptive immune responses are deregulated in individuals with obesity and are key drivers of its associated metabolic alterations. Although the anti-inflammatory growth differentiation factor 15 (GDF-15) is a candidate protein against obesity, its mechanisms regulating the immune responses are not fully cleared. We examined whether GDF-15 was related to serum immunoglobulins in a children's cohort assessed longitudinally during childhood. Results showed that circulating GDF-15 positively associated with IgA (p

Immunoglobulin A deficiency (IgAD) is the most common primary immunodeficiency in the general population. It is defined as a serum IgA level below or equal to 0.07 g/l with normal IgM and IgG levels in children over the age of 4. However, a few cases of reversal of IgAD at later ages have been observed previously, especially in pediatric patients. This study aimed at investigating the frequency of reversal in a large cohort of children and young adults in order to evaluate the present definition of IgAD. Clinical laboratory records from 654 pediatric IgA deficient patients, 4-13 years of age, were retrieved from five university hospitals in Sweden. Follow up in the children where IgA serum levels had been routinely measured was subsequently performed. In addition, follow up of the IgA-levels was also performed at 4, 8 and 16 years of age in children who were IgA deficient at the age of 4 years in a Swedish population-based birth cohort study in Stockholm (BAMSE). Nine out of 39 (23.1 %) children who were identified as IgAD at 4 years of age subsequently increased their serum IgA level above 0.07 g/L. The average age of reversal was 9.53 +/- 2.91 years. In addition, 30 out of the 131 (22.9 %) children with serum IgAD when sampled between 5 and 9.99 years of age reversed their serum IgA level with time. The BAMSE follow up study showed a reversal of IgAD noted at 4 years of age in 8 out of 14 IgAD children at 16 years of age (5 at 8 years of age) where 4 were normalized their serum IgA levels while 4 still showed low serum levels of IgA, yet above the level defining IgAD. The results indicate that using 4 years of age, as a cut off for a diagnosis of IgAD may not be appropriate. Our findings suggest that a diagnosis of IgAD should not be made before the early teens using 0.07 g/L of IgA in serum as a cut off.

Giardiasis is a gastrointestinal infection of wide distribution that is more prevalent in childhood. Easy and rapid diagnosis of giardiasis is essential for reduction of this infection. This cross-sectional study included 62 children in which collection of saliva, stool and serum samples was performed. An enzyme-linked immunosorbent assay (ELISA) technique was evaluated to detect IgA and IgG responses in both saliva and serum samples. Twenty-two children were positive for Giardia duodenalis infection by direct examination of faecal specimens, 20 non-infected and 20 infected with other parasites. Salivary and serum IgA and IgG responses against G. duodenalis infection were significantly higher in Giardia parasitized than non-Giardia parasitized children (p < 0.001). This concludes that specific salivary IgA may serve as a diagnostic tool and specific salivary IgG as a screening tool in monitoring the exposure of various populations to Giardia duodenalis. The advantage of salivary assays over serum immunoglobulin assay is being easy and non-invasive in sampling technique which is important especially for young children.

An increased prevalence of immunoglobulin (Ig) A deficiency has been documented in a number of autoimmune diseases; however, its association with type 1 diabetes mellitus (DM1) is a subject of debate. This study was performed to evaluate serum IgA levels in a group of pediatric patients with DM1. Three hundred patients with mean age of 12.6 ± 6.7 years were enrolled in this study. Serum IgA and other immunoglobulins levels were measured using enzyme-linked immunosorbant assay. Mean serum IgA level of patients was 271.0 ± 141.4 mg/dl. Only two patients had IgA deficiency (IgA

Serum IgA antiendomysial antibodies (EmA) were found in 61 (87%) of 70 adults and children with untreated celiac disease, whereas IgA antigliadin antibodies (AGA) and IgA R1-antireticulin antibodies (R1-ARA) were positive in 71% and 47%, respectively, of the same patients. Two of the nine untreated celiacs negative for IgA EmA showed positivity for IgA AGA. While IgA AGA and R1-ARA disappeared in all the celiacs, tested one year after gluten-free diet, IgA EmA persisted at low titer in seven (18%) of these 38 subjects, although the jejunal biopsy showed a complete regrowth of jejunal villi. All the disease control patients as well as the blood donors tested were always negative for the three IgA antibodies. Our results state that the search for both IgA EmA and AGA gives the best results in the screening of celiac disease, since the positivity for at least one of these two antibodies allows identification with a 100% specificity of the 90% of untreated celiac patients.

The concept of oral tolerance is based on work in experimental animals, but data demonstrating its hypothesized existence in humans is scarce We enrolled 25 healthy term newborns with nonatopie heredity to a prospective study, during; which scheduled visits took place at 3, 6, and 11 mo of age. Diet was determined at each visit Gut humoral immune response was approximated with ELISPOT assay of circulating antibody secreting cells, and serum 1gM, IgA and IgG antibodies to cow milk antigens were measured At 3 mo of age, despite low levels of serum IgA antibodies, cells secreting specific IgA to cow milk antigens were detected in the formula fed group, but not in breastfed infants The number of these cells decreased between the 6 and 11 mo visits, remaining at a measurable lesel. The total number of IgA secreting cells increased with age (p=0.001) The milk in the infant's diet inlluenced this development the age related increase was significantly greater in the formula fed group (p=0.04). The results indicate that diet significantly affects the developing immune system. Further, healthy infants, unlike those with cow milk allergy, are able to produce a local antigen specific immune response to dietary antigens. This could be crucial in attaining clinical tolerance of such antigens

Forty-nine out of 54 male workers engaged in the production of an epoxy compound, t-methyl-3-phenylglycidate, showed skin symptoms in varying degrees that may be due to the skin-irritative effect of the compound. The exposed workers were also shown to have subjective symptoms which may be related to the irritative property of the compound on surface tissue. Laboratory examinations on the blood obtained from the exposed workers showed significantly higher values of leukocyte concentration as compared with the non-exposed controls. This was chiefly caused by the increase of neutrophilic granulocytes and T-cell lymphocytes. Serum IgA levels of the exposed workers were shown to be significantly lower than those of the control group. Hemoglobin concentration, hematocrit value and red cell count of the exposed workers remained at the same level as those of the control subjects. Liver or kidney damage was not found in biochemical analyses on the sera of exposed workers.

The serum IgA in young infants (6-240 days old) comprised a much larger proportion (means = 36%; range, 7.5-72%) of polymeric IgA than in normal adults (means = 13%; range, 4.7-22%), but with a normal subclass distribution. In contrast, in IgA-deficient adult serum, there was a higher proportion (means = 34%; range, 16.3-38%) of IgA2 than in normal adult serum (means = 21%; range, 5-36%), with, however, a normal proportion of polymers. The distribution of IgA subclasses in the separated monomeric and polymeric IgA fractions was similar to that in unfractionated sera. The proportions of IgA polymers and IgA2 in serum are unlinked parameters, suggesting that both do not necessarily represent mucosal contributions to blood IgA.

Two of three brothers with the classical signs of ataxia telangiectasia were investigated for their immunological disorders at the ages of 13 and 16 years, respectively. The elder brother also suffers from autoimmune hemolytic anemia, a complication which has not yet been described in the course of ataxia telangiectasia. Immunological investigations made in both brothers showed a reduction in the number and function of T lymphocytes. The number of B lymphocytes was normal, among which there were cells staining for IgA, although serum IgA was absent. It seems possible that this phenomenon is caused by a disturbance in the process of maturation of lymphoid cells with a lack of differentiation into IgA-synthesizing plasma cells.

Nineteen out of 83 children with asymptomatic haematuria were classified as having IgA glomerulonephritis, characterized by diffuse mesangial deposition of IgA in the absence of systematic disease. Different histological patterns were observed: i.e., minor glomerular lesions (5 cases), focal and segmental proliferative glomerulonephritis (8 cases) and diffuse proliferative glomerulonephritis (6 cases). Recurrent gross haematuria is the clinical hallmark of the disease. Proteinuria was present in 14 children and exceeded 1 g/m2/day in 3 patients. Clinico-pathological correlations showed a close relation between the degree of proteinuria and the histological lesions. Serum IgA levels were elevated in 3 children. Glomerular filtration rate remained above 80 ml/min/1.73 m2 in a 1 to 9 year follow-up.

We have developed two ELISA methods, i.e., enzyme immunoassay (EIA) and fluorescence immunoassay (FIA), for the semiquantitative detection of specific IgA and IgG antibodies directed against alpha-gliadin. The tests differ only for the enzyme substrate and, when optimized, could be used in large routine screening of celiac disease. Several serum samples from patients with celiac disease and gastrointestinal disorders as well as from control subjects were tested. Both methods gave good correlation with clinical data, were easily performed and had some specificity features, while FIA proved to be more sensitive.

Phenytoin has been shown to induce serum IgA deficiency in patients with epilepsy. We have followed 37 phenytoin-treated patients with reduced serum IgA concentrations for 2-7 years. All anti-epileptic drug treatment was withdrawn in 8 patients. Phenytoin was substituted by other anti-epileptic drugs in 13 patients. Sixteen patients received phenytoin unchanged. The mean serum IgA concentration increased from 0.14 g/l to 0.71 g/l in the patients off drug treatment, and from 0.20 g/l to 0.84 g/l in the patients changing to other drugs. The mean IgA concentration increased from 0.21 g/l to 0.37 g/l in the patients with phenytoin unchanged, due to the increase of the IgA levels in a few patients who initially showed a slightly depressed IgA concentration. The overall increase of IgA concentrations was significant. When tested separately in each patient group, the difference was significant for the patients off all drugs, and for those changing from phenytoin to other drugs. The IgM concentration increased significantly when all patients were considered together. This was due to the increase of IgM in the patients no longer receiving phenytoin therapy. Withdrawal of phenytoin did not influence the IgG concentrations.

The significance of chlamydial serum IgA compared with IgM and IgG in the diagnosis of urogenital chlamydial infection was evaluated using 120 sera from different categories of patients. In urethritis patients both IgM and IgA antibodies were not found to be present consistently, whereas in patients with deep-seated chlamydial infection, IgA was more often present. Although of limited value in superficial infections, demonstration of IgA antibodies may be of value in the diagnosis of deep-seated chlamydial infections.

IgA protease produced by various strains of Haemophilus influenzae can digest serum IgA and yield its fragments which can react with anti-IgA serum. We assayed IgA protease activity by detecting the digests of IgA by SDS-PAGE and immunoblotting. The digests were separated with SDS-PAGE, transferred to nitrocellulose membranes and detected with anti- (alpha chain of human IgA, its Fab and its Fc) immunoglobulin conjugated peroxidases. Using this method, we can determine which type of IgA protease is produced by various of H. influenzae strains. All the 20 strains isolated from respiratory tracts produced IgA protease.

A MAJOR, poorly characterized component of human tears migrates more anodally than serum albumin in electrophoresis1. Erickson termed this protein “tear albumin”. When they carried out immunoelectrophoresis of human tears with rabbit anti-human tear serum, Josephson and Lockwood2,3 obtained a precipitin line in the albumin region. This line did not disappear when the anti-tear serum was absorbed with normal human serum. These results1–3 did not exclude the possibility that the tear albumin was a modified form of the albumin or prealbumin found in serum, as was the case with secretory IgA, which consists of serum IgA attached to a “transport piece”4.

ALTHOUGH the amount of IgA in serum is small compared with the amount of IgG, IgA is predominant in secretory fluids such as colostrum, saliva, nasal fluid and tears1–3. IgA from the colostrum and saliva4 has a higher sedimentation constant (11S) than serum IgA (7S), and 11S colostral IgA has additional antigenic determinants with specificities which are not present in serum IgA. In addition to the heavy (α) and light chains present in the molecule of serum IgA, colostral IgA has another protein component—the transport piece5.

Quantitative serum immunoglobulins were determined in 19 children with ITP, 13 acute and 6 chronic by single radial immunodiffusion method. Although IgG and IgM values did not differ, IgA levels were found uniformly lower than the proper controls, which stayed lower in remission, since autoimmune disorders occur more frequently in patients with IgA deficiency and low IgA levels were observed more frequently in those families, some relation between low serum IgA and ITP is suggested.

Three molecular forms of IgA, monomeric (mIgA), polymeric (pIgA), and secretory (sIgA) make up approximately 85,15, and 1% of the IgA in adult serum. IgA concentration in secretions (sIgA) increases with age more rapidly than serum IgA. To evaluate the development of the IgA system, we measured total IgA, pIgA, and sIgA in the serum of infants 3-54 weeks of age. PIgA was measured by an enzyme-linked immunoassay based on the binding of pIgA to solid phase free secretory component. Total IgA and sIgA were measured by immunofluorescent assays. PIgA measurements in 10 normal adults sera (13±4mg/dl or 7%±2 of the total IgA) were similar to those reported using assays based on prior separation of the IgA forms. The pIgA concentration in infants' sera ranged from 3.2 to 27.9mg/dl. They increased from ½ to full adult levels over the first year of life. The pIgA was 10 to 75% of the total IgA in the infants' sera. The proportion of pIgA decreased with age due to an increase in mIgA. SIgA concentration ranged from 0 to 5.3mg/dl (0 to 28.9% of the total IgA) and did not correlate with age. These studies suggest that the various forms of serum IgA develop from pathway which mature at different rates. This is in keeping with the predominance of pIgA in the serum of many lower animal species. Alternatively, the relative predominance of high molecular forms of IgA in infants' sera may be due to immaturity of the mechanisms for removal of these forms of IgA.

Oxelius et al reported that combined deficiency of IgA, G2 and G4 is associated with recurrent respiratory tract infections, whereas IgA deficiency without IgG subclass deficiency is asymptomatic. They suspect G2 deficiency results in defective responses to polysaccharides, increasing susceptibility to infection. Studies in our laboratory indicated that isolated deficiency of G4 results in similar susceptibility to infection. To investigate IgA-G2-G4 interrelationships, we measured serum G2 and G4 in 59 subjects who had a primary diagnosis of IgA deficiency. We found G2 decreased ( 5 mg/ml) in 9. G4 was decreased ( 0.8 mg/ml) in 1. Thus IgA deficiency commonly is associated with disturbed synthesis or catabolism of G2 and/or G4. In 9 of 17 with severely depressed G2, G4 was also severely depressed. Similarly, 9 of 15 with severely depressed G4 also had very low G2. One patient had IgA deficiency and frequent infections without either G2 or G4 deficiency. One with hyper IgE syndrome had depressed G2 and very high G4. Forty-four G4 deficient patients in whom IgA levels were unknown were also studied. These had a high incidence (64%) of G2 deficiency, 30% severe. It is apparent that determination of IgG subclasses, particularly G2 and G4, is important in the evaluation of patients with recurrent infection, especially if levels of IgA are low or when levels of all major immunoglobulin classes are normal.

Top of pageAbstract Serum IgA against gluten is a good marker of untreated coeliac disease, especially in children. In this study a new test (Pharmacia Gluten IgA EIA) was evaluated. Assay was performed in microstrips which were gliadincoated. Total test time

Y. enterocolitica requires iron for growth making thalassaemic chilren susceptible to infections with this organism. In order to investigate the hypothesis that a common mucosal immune system exists in man, serum and salivary antibodies to Y.enterocolitica O3 and serum antibodies to E.coli and B.vulqatus were measured by ELISA in Greek Cypriot thalassaemics and controls. Serum IgG antibody levels to Y.enterocolitica O3 were raised in 17/47 thalassaemics compared to 3/37 controls [p=0.006]. Serum IgA antibody levels were raised in 13/47 thalassaemics compared to 2/37 controls [p=0.018]. Serum IgM antibody levels were not significantly different in patients and controls. However serum IgG, IgA and IgM antibody levels to E.coli and B.vulqatus were not significantly different in thalassaemic patients compared to controls. Several thalassaemic patients also had raised salivary antibody to Y.enterocolitica indicating either transfer of IgA from serum to secretions or local salivary IgA production by B cells which have migrated there from the gut. It is concluded that a subset of Greek Cypriot thalassaemic patients have high antibody levels to Y.enterocolitica O3 indicating prior infection and that the presence of salivary antibodies to Y.enterocolitica provides preliminary evidence to support the hypothesis that a common mucosal immune system exists in man.

PATIENTS AND METHODS 133 patients with anaphylactoid purpura between Jan. 1960 and Dec. 1979 were retrospectively reviewed in regard to renal involvement. Renal involvement were 41 cases (30.8%). Their clinico-patho-immunological correlation were analized, as follows. 1) Clinical, pathological classification and their prognosis. 2) Correlation with streptococcal infection, serum IgA. and complement. 3) Presentation of 2 patients with CRF. RESULTS The group; AGN 46%, CGN 34%, NS 17%, CRF 2.4%, RPGN 0% The clinical manifestation and the pathological diagnosis were compaired. The patients of 52.1% had positive ASLO titer. Positive throat swab culture ; 23%. 80% had high or significant increase in the value of Ig A and C3, but there was no significant difference between every groups. In the series two patient with NS went on to develop chronic renal failure.

IgA deficiency is the most common humoral immune defect. We examined blood lymphocytes from 4 patients with Ataxia Telangiectasia and 6 with common IgA deficiency. All had absent serum IgA but .5–2% sIgA+ circulating B cells. PWM and EBV were used for the stimulation of these cells either in high density cultures (106 cells/well) or in low density, limiting dilution cultures (1–104 cells/well), which restrict cell:cell interactions. IgG, A and M secreted into culture supernates was measured by RIA and ELISA after 8 d (PWM) or 4 wk of culture (EBV). Cells from patients failed to produce IgA in high density cultures. In EBV stimulated limiting dilution cultures, IgA producing cells were detected in all patients. The frequency of IgA-committed, EBV transformable cells was normal in patients with uncomplicated IgA deficiency (approximately 1/100 B cells). However, in patients with AT, the frequency of IgA producing cells was up to 40 times lower. Our experiments demonstrate the presence of IgA producing cells in all patients with IgA deficiency studied. No evidence for IgA specific B cell defects could be delineated in common IgA deficiency. In AT, abnormalities of B cell differentiation may lead to the development of a smaller, IgA-committed B cell compartment. Supported by the Arthritis Society, MRC and NCI of Canada.

Current evidence suggests that CIC are involved in the pathogenesis of HSP, and several studies have demonstrated both IgA and IgG containing CIC in patients with HSP. Recent work from this laboratory showed that over 50% of children with HSP have IgA RF. The present study was performed to investigate the role of IgA RF in the formation of IgA containing CIC in HSP, and to determine the subclass composition of IgA RF. CIC were isolated from the sera of 22 children with HSP and 13 controls by means of polyethylene giycol (PEG) precipitation. The percentage of IgG, IgA, and IgM precipitated by PEG was significantly greater in HSP patients than controls (P

The maturation of the serum IgA system is slow in comparison to IgG and IgM. Adult serum IgA levels in normal children are reached only at the age of ten years. The normal range is broad and individual fluctuations marked. To investigate the maturation of the system and the implications of low serum IgA in infections of the respiratory and gastrointestinal tract as well as the ORL system we reexamined 19 children once found in our laboratory to be deficient in serum IgA. We tested serum IgA, IgA and secretory component in tears of these 19 children. 53% of them showed normalization of these parameters, 26 % had low serum IgA while 4 children remained deficient. Maturation and compensatory mechanisms are discussed.

The secretory defense system (SDS) provides antimicrobial activity to mucous surfaces. Tears were used as the representative secretion of the SDS because of a high protein content and ease in obtaining reproducible samples. Tears were obtained with crying or after stimulation with salt; serum was also obtained. The components of the SDS were evaluated in 25 normals, 9 newborns, and 25 patients with increased susceptibility to infection and included assay for: 1) immunoglobulins, 2) protein, 3) isoagglutinins (anti-A, anti-B), 4) lysozyme and 5) complement (C). In normal adults, mean IgG level was 17 mg%, IgA 11 mg%, IgM and C absent, total Ig 28 ± 7 mg%. Mean protein was 11.8 mg/ml, lysozyme 2.0 mg/ml, isoagglutinin titers 1:8. Tear IgG was correlated with serum IgG; tear IgA was not correlated with serum IgA. SDS abnormalities were noted in newborns, in patients with serum antibody deficiencies, and in 4 patients with increased susceptibility to infection and normal serum immunoglobulins. Newborn tears are low in protein, IgA, isoagglutinins, and lysozyme (mean .62 mg/ml) but have normal IgG. Other patients with SDS abnormalities had low total Ig in the tears (

Familial cases of selective immunoglobulin A deficiency have been documented, but the mode of inheritance remains unsettled. The propositus of the present study, a 9-year-old girl with a past history of frequent upper respiratory tract infections, had an unusually low serum IgA level, between 0.5 and 2.0 mg/100 ml (i.e., IgA detectable by double diffusion but not by the radial immunodiffusion technique). The mother of the patient showed a total lack of serum IgA and suffered from chronic urinary tract infection. The father and brother of the propositus and the maternal relatives tested had normal IgA levels. Bothe patients had normal karyotypes. In the propositus. IgA was detected in saliva and intestinal juice, but IgM was present in higher concentrations in these secretions. Direct immunofluorescent studies of both rectal and small intestinal mucosa revealed IgA-containing cells, but IgM-containing cells were predominant. In the mother, no IgA was detectable in whole saliva concentrated 20 times, and the rectal mucosa was completely devoid of IgA-containing cells, whereas IgM-containing cells were abundant. These findings suggest that IgA deficiency may differ in degree of severity. The daughter in this family could be heterozygous for a recessive trait, while the mother is homozygous. On the other hand, an autosomal dominant mode of transmission with variable gene expressivity cannot be ruled out.