Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “IgA Deficiency”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 55 records · Page 3Linked to original sources
PubMed1984

Systemic antibody deficiency in patients without serum immunoglobulin deficiency or with selective IgA deficiency.

Serum IgG tetanus toxoid antibody (IgGTTab) concentrations were measured in patients with chronic chest infections or recurrent acute chest infections following immunization and compared with results obtained in a group of 43 controls. Apart from selective IgA deficiency in some patients, all had normal or high serum immunoglobulins. Using an enzyme linked immunosorbent assay (ELISA) for IgG TTab, antibody was present following one immunization in all controls who had previously been immunized and following two immunizations in those not previously immunized. Ninety-seven and a half per cent of controls had a serum antibody concentration of greater than 4 micrograms/ml. Following the same immunization schedule, eight of 45 (18%) patients with chronic chest infections and three of 11 (27%) patients with recurrent acute infections had a serum IgG TTab of less than 4 micrograms/ml. The three patients with a low IgG TTab concentration and recurrent acute infections all had selective IgA deficiency. Two of these patients have benefited from injections of normal human immunoglobulin. It is suggested that systemic antibody deficiency as a cause of chronic or recurrent respiratory tract infections cannot be excluded by measuring serum immunoglobulin concentrations alone and that it is of value to measure antibody responses following immunization.

Adult↗
PubMed1986

Analysis of the gastrointestinal secretory immune barrier in IgA deficiency.

Secretory IgA is known to play a major role in the exclusion of foreign antigens from the systemic compartments. We have previously shown that IgA-deficient subjects can have large amounts of circulating immune complexes containing bovine antigens of dietary origin, presumably due to the defective secretory barrier. In these studies, we investigated whether the peak amount of immune complexes found after specific antigen challenge could be related to the level of serum or salivary IgA. Our data show that the peak of immune complex is not related to either serum or salivary IgA but that it is closely correlated to the titer of antibody to milk proteins. In addition, it appears that some individuals with only modest IgA deficits can have substantial mucosal permeability defects on milk challenge.

Adolescent↗
PubMed2005

Bronchial hyper-responsiveness in selective IgA deficiency.

Secretory IgA in mucosal secretions has a broad protective function. The insufficient protection provided by the respiratory mucosa in children with selective IgA deficiency (sIgAD) might facilitate the development of bronchial hyper-responsiveness (BHR) and consequently asthma symptoms. This study was conducted to clarify the prevalence of BHR in sIgAD children and the relationship with atopic status. A cohort of 20 children (group A) aged 6.4-20.1 yr (median: 12.6) with sIgAD (serum IgA <6 mg/dl) were evaluated for BHR using inhaled hypertonic saline test as well as for atopy by skin prick testing (SPT) to eight common aero-allergens. Seventy other children with normal levels of serum IgA, but sensitized to aero-allergens (group B) and 102 with normal IgA and negative SPTs (group C) were also evaluated. Baseline spirometry demonstrated that forced vital capacity (FVC) values in group A were significantly lower than in C. Forced expiratory volume in 1 s values were similar in all groups, but impairment of the forced expiratory flow over the middle half of the FVC was detected in group B. The prevalence of BHR was similar among group A (30.0%) and group B (35.7%) (p = 0.79) but they differed from group C (5.9%) (p = 0.005). An association between BHR and reported current (p = 0.001) but not lifetime asthma symptoms among group A was also observed. There was no association between atopy and BHR in group A but only to mites' sensitization (p = 0.03). In conclusion, these results indicate that sIgAD constitutes a risk factor for development of BHR but it appears to be related to sensitization to mites.

Adolescent↗
PubMed2006

Class switch recombination in selective IgA-deficient subjects.

Selective IgA deficiency is a common immunodeficiency in Caucasians, but the molecular basis of the disorder remains elusive. To address this issue we examined the molecular events leading to IgA production. Naive IgD positive B cells were purified from four donors with IgA deficiency and four control donors, all Caucasians. Stimulation of B cells from IgA-deficient donors with the cytokines transforming growth factor (TGF)-beta, interferon (IFN)-gamma or interleukin (IL)-10 in the presence of anti-CD40 antibodies showed reduced expression of both activation-induced cytidine deaminase (AID) and alpha germline transcripts (GLT) compared to controls. It was possible, however, to induce AID and alpha GLT when stimulating the cells with anti-CD40 antibody and TGF-beta in the combination with IL-10. Moreover, in anti-CD40 antibody-stimulated cultures, addition of IL-10 or IL-10 + TGF-beta in combination, induced IgA production, albeit lower than found in B cells from controls. The B cells from the IgA-deficient subjects were less effective in differentiating into CD138(+) X-box binding protein 1 (XBP-1)(+) plasma cells when stimulated with TGF-beta, IFN-gamma or IL-10. Interestingly, when adding IL-4 to TGF-beta alone or in combination with IL-10, the immunoglobulin production in B cells from IgA-deficient donors was comparable with those of normal controls. These data show that in healthy subjects in vitro IgA production can be up-regulated by addition of IL-10 to CD40-stimulated B cells, whereas a similar B cell differentiation does not occur in IgA-deficient subjects. Addition of IL-4, however, reverts this abnormality.

Adult↗
PubMed2001

[Autoantibodies in relatives of IgA-deficient patients].

Selective IgA deficiency is frequently associated with autoimmune phenomena. We addressed the question, whether autoantibodies are more frequent in relatives of IgA deficient persons. Fifteen first-degree relatives of patients with a familial form of IgA deficiency and 129 first-degree relatives of patients with a sporadic form of IgA deficiency were evaluated. Following autoantibodies were detected: antinuclear, anti-thyreoglobulin, anti-thyroid microsomal, anti-gastric parietal cell, anti-reticulin, anti-smooth muscle, anti-mitochondrial, anti-neutrophil cytoplasmatic, anti-cardiolipin, rheumatoid factor and antibodies against gliadin. We did not find increase in any of the autoantibodies evaluated in any groups of patients. Our results do not support a significant genetic influence in autoantibodies formation in selective IgA deficiency.

Adolescent↗
PubMed1995

Linkage of IgA deficiency to Gm allotypes; the influence of Gm allotypes on IgA-IgG subclass deficiency.

IgA deficiency (IgAD) is the most common immunodeficiency, characterized by an arrest in B cell differentiation. It has a sporadic occurrence or variable inheritance pattern, and is also linked to the HLA genes. IgA deficiency is sometimes associated with IgG subclass deficiency. In this study the Gm allotypes, as genetic characteristics of the IgG1, IgG2 and IgG3, were analysed in 83 Caucasian IgAD individuals. Half of the patients presented with IgG4 < 0.01 g/l compared with 5% (P < 0.001) in a healthy population. Three of the 83 had significantly low IgG2 and four had significantly low IgG3 levels. Gm allotype frequencies in IgAD deviated compared with a normal population. Of the 83 patients, 44 (53%) showed homozygous G2 m(",") expression on the IgG2 locus (33% in controls, P < 0.01). In IgAD the Gm(a,",g) haplotype was more frequent (43%) compared with controls (31%, P < 0.01). The Gm homozygous phenotype Gm(a,",g/a,",g) was most common, found in 20 of 83 patients (24%, P < 0.05) compared with controls (14%). On the other hand the Gm(f,n,b) haplotype of IgAD was rare (28%) compared with controls (45%, P < 0.001). The low IgG4, < 0.01 g/l, found in 50% of the patients, was even more frequent (56-69%) among the G2 m(",") phenotypes. IgG subclass levels were given for different Gm phenotypes of the IgAD group and compared with controls. Significantly low IgG4 was revealed in the Gm(a,",g/a,",g) phenotype (P < 0.01) and significantly low IgG2 in the Gm(a,",g/f,",b) phenotype (P < 0.01). The Gm(a,",g/f,",b) phenotype contained the three patients found with IgG2 levels < -2 s.d., and the four patients with IgG3 levels < -2 s.d. were present among those with the homozygous Gm(a,",g/a,",g) phenotype; both phenotypes with G2 m(",") on the IgG2 locus. The 'compensatory' increase of IgG was significant for both IgG1 and IgG3 in all Gm phenotypes, but in the Gm(a,",g/f,",b). Thus, the susceptibility of IgAD with the additional IgG antibody deficiencies, down-regulated IgG4 and IgG2/IgG3, is associated with Gm allotypes, especially the homozygous G2 m(",") expression on the IgG2 locus.

Hemagglutination Inhibition Tests↗
PubMed1980

Heavy chain-specific suppression of immunoglobulin synthesis and secretion by lymphocytes from patients with selective IgA deficiency.

A simple, solid-state immunofluorescent assay specific for the heavy chain of human immunoglobulins (Ig) was adapted for studying pokeweed mitogen- (PWM) stimulated Ig biosynthesis and secretion by peripheral blood lymphocytes (PBL) in vitro. PBL from patients with panhypogammaglobulinemia were noted to synthesize and secrete decreased amounts of all classes of immunoglobulin after polyclonal activation of B cells in vitro with PWM. PBL from 14 patients with selective deficiency of IgA were capable of synthesizing and secreting significant levels of IgG and IgM after culture with PWM; however, they did not produce appreciable amounts of IgA. Thus, B lymphocyte differentiation in vitro parallels the clinical status. Several different immunoregulatory phenomena were observed when PBL from patients with selective IgA deficiency were co-cultivated with cells from healthy donors. Most notable was the specific suppression of IgA synthesis and secretion seen in 8 of 14 patients studied, although other modulatory effects including enhancement and suppression of all Ig classes were also observed. These results suggest that the pathologic basis of selective IgA deficiency may be heterogeneous and support a model for the role of Ig class-specific suppressor cells in the pathogenesis of some cases of selective IgA deficiency.

Cells, Cultured↗
PubMed1991

Familial selective IgA deficiency with circulating anti-IgA antibodies: a distinct group of patients?

Two families were investigated in which the mothers had selective IgA deficiency and circulating class-specific anti-IgA antibodies. Both gave birth to two children who were found to be IgA deficient. Three of these children developed anti-IgA antibodies before puberty. In vitro immunoglobulin production studies performed in the children of both families revealed an IgA B cell defect combined with IgA-specific excessive T suppressor function in all four. The mechanisms by which transplacental passage of maternal anti-IgA antibodies could have interfered with the developing IgA system in the offspring are discussed.

Adult↗
PubMed1995

Reduced serum level of transforming growth factor-beta in patients with IgA deficiency.

Seventeen patients with IgA deficiency, 13 subjects with selective IgA deficiency and 4 with a combined IgA and IgG2 deficiency, were assessed for serum levels of cytokines relevant for B cell differentiation. Transforming growth factor (TGF)-beta was quantified by bioassay and interleukin (IL)-4, IL-6, and IL-7 by immunoassay. The serum levels of TGF-beta were significantly lower in patients with IgA deficiency than in healthy blood donors. Of the patients with IgA deficiency, 4 had detectable IL-4 levels while 4 of the others had detectable IL-6 levels in serum. IL-4 and IL-6 were not detected in the controls. Serum IL-7 levels were similar in patients and controls. A significant, negative correlation was found between serum TGF-beta and the number of circulating B lymphocytes in the patients with IgA deficiency. No association was found between serum cytokine levels and the occurrence of infections at the time of study. Since TGF-beta has been implicated in IgA isotype switching in man, and our study demonstrates an association between low serum TGF-beta levels and IgA deficiency, dysregulation of TGF-beta might be a contributing factor in the pathogenesis of IgA deficiency.

Adult↗
PubMed2006

Dermatitis herpetiformis and partial IgA deficiency.

Although the specific IgA autoantibody responsible for the pathogenesis of dermatitis herpetiformis (DH) is unknown, the presence of IgA is considered essential in the pathogenesis of DH. To date, no cases of IgA deficiency have been reported in DH. In contrast, IgA deficiency is found in 2% to 3% of patients with celiac disease, a rate 10 to 15 times higher than the normal population. We report 2 patients with DH who also have partial IgA deficiency. We evaluated the sera of these patients for the presence of IgA autoantibodies to endomysium, tissue transglutaminase, epidermal transglutaminase, and gliadin. Both patients were found to have IgA endomysial and tissue transglutaminase antibodies, and serologic markers for DH. Corresponding IgG autoantibodies were not useful serologic markers of DH in the setting of IgA deficiency, as they often are in celiac disease. We then screened 98 DH sera for total IgA levels and identified 1 additional case with IgA deficiency. In conclusion, DH may develop in patients with partial IgA deficiency, indicating that pathogenically directed IgA antibodies are likely sufficient for cutaneous IgA deposition in this disease.

Adult↗
PubMed2004

Oral manifestations in selective IgA deficiency.

Selective immunoglobulin A (IgA) deficiency is the most common of the primary immunodeficiencies with a frequency of 1/300-1/3000, depending on the screened population. As secretory IgA (SIgA) has a protective role in mucosal surfaces from invasion of microorganisms, it is thought that IgA-deficient subjects are susceptible to periodontal diseases and oral manifestations. Previous studies show contradictory results, concerning the involvement of the individuals' periodontium with IgA deficiency. The aim of this study was to investigate and compare the oral manifestations in IgA-deficient subjects with controls. Eleven selective IgA-deficient subjects aged 3-18 years with serum IgA levels <10 mg dl(-1) and 11 age-sex-matched healthy children as the controls entered the study. Oral mucosal investigation, dental caries, plaque accumulation and periodontal status were assessed. Serum immunoglobulin levels were measured by single radial immunodiffusion (SRID) method. Saliva immunoglobulins and secretory component levels were measured by enzyme linked immunosorbent assay (ELISA) methods. IgA-deficient patients had serum and saliva IgA levels less than 10 mg dl(-1) and 10 microg ml(-1), respectively, but other serum immunoglobulin levels were normal and saliva immunoglobulin M (IgM) levels were increased, compared with controls. There were no significant differences in oral manifestations between IgA-deficient subjects and controls, which may be a result of compensatory increase of saliva IgM or other non-immunological defence factors in saliva. Thus, it is not necessary to evaluate IgA and SIgA in all the patients with oral and dental lesions and it is thought that it is better to investigate other factors.

Adolescent↗
PubMed1985

Family studies of IgA deficiency.

Seventeen immunoglobulin A (IgA)-deficient subjects and other members from 13 families were examined at HLA-A, B and DR, C4A, C4B, and Bf loci. Of the 29 independent haplotypes in the IgA-deficient subjects, 22 included deletions, duplications, or defects at the C4 or 21-hydroxylase loci. It is suggested that there may be a gene regulating serum IgA concentrations in this same region of chromosome 6. Three main supratypes explain most of the previously reported HLA associations with IgA deficiency. These are A1, Cw7, B8, C4AQ0, C4B1, BfS, DR3, Bw65(14), C4A2, C4B1/2, BfS, and Bw57(17), C4A6, C4B1, BfS. All three are proposed to carry a gene for IgA deficiency, while other supratypes carrying the same B allele generally do not. Other supratypes possibly associated with IgA deficiency were also identified. A survey of about 150 individuals with at least 1 of the 3 main supratypes revealed only 2 IgA-deficient subjects, and these were among the 20 that had 2 of these supratypes. This suggests the possibility of a recessive mode of inheritance, with penetrance determined by another factor which is not major histocompatibility complex-linked. All the supratypes found in this group of IgA-deficient subjects would then carry the putative recessive allele for IgA deficiency.

Alleles↗
PubMed1991

Extrahepatic bile duct growth in mice repeatedly injected with human normal serum, IgA-deficient serum or purified secretory IgA.

Another group of researchers has reported that seven intraperitoneal injections into mice of purified human serum IgA or normal human serum--but not IgA-deficient serum, mouse serum or saline--induced considerable growth of the extrahepatic bile duct epithelium. They stated that heterologous IgA was principally responsible for this effect. We have quantitated this growth by another method: enumeration of total and radiolabeled nuclei of the lumenal and glandular epithelium in transverse duct sections after tritiated thymidine injection and autoradiography. Our data show maximal incorporation between 18 and 24 hr after the last injection, with the highest labeling index in the lumenal epithelium after only three injections and before any duct enlargement. After four to seven injections, thymidine incorporation continued in juxtalumenal glands, together with massive glandular proliferation into the thickening wall and obvious inflammation. These changes were more pronounced in the liver-proximal part of the duct without affecting intrahepatic duct and gallbladder epithelia. Subcutaneous serum injections were less active. We confirm the inactivity of buffered saline, but, unlike previous authors, demonstrate strong activity in purified human milk secretory IgA and in IgA-deficient serum. We suggest that this different approach of quantitating epithelial proliferation will allow comparison of the bile duct growth effects of different, well-characterized human and animal IgA preparations.

Animals↗