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Biomedical subjects

V A Oxelius

Publications and source records attributed to V A Oxelius.

At least 19 recordsLinked to original sources

Antibody response to the Haemophilus influenzae type b-tetanus toxoid conjugate vaccine in healthy and infection-prone individuals with IgG3 subclass deficiency.

Searching for a possible explanation for the phenotypic heterogeneity in IgG3 deficiency, we studied the antibody response to a polysaccharide and a protein antigen in IgG3-deficient (IgG3d) adults after vaccination with Haemophilus influenzae type b capsular polysaccharide (Hib CP) conjugated to tetanus toxoid. Distribution of isotypes, idiotypes, clonotypes, and Gm allotypes were compared. All the vaccinated individuals, irrespective of the level of IgG3 and proneness to infections, developed protective levels of anti-Hib CP. Significantly lower prevaccination levels of IgG2 (p < 0.05) and IgG4 anti-Hib CP (p < 0.04 and p < 0.03) were noted among the infection-prone compared to the healthy IgG3d individuals and/or controls. Seventy percent of the IgG3d patients and none of the controls had the low responding Gm(ga-n/ga-n) genotype, while the majority of the controls had the alternative Gm(bfn/bfn) genotype. The conjugate ACT-HIB vaccine efficiently overcomes the IgG3 subclass deficiency state and the genetic predisposition for lower responsiveness, providing protection against Hib and tetanus infections. The proneness to infection in some IgG3d individuals may relate to their low prevaccination antibody levels.

Enzyme-Linked Immunosorbent Assay↗

[Ataxia-telangiectasia surveyed in Sweden].

Ataxia-telangiectasia (AT) is a rare autosomal recessive disease with a complex phenotype involving cerebellar degeneration, immunodeficiency, cancer risk and radiosensitivity. Our aim has been to identify Swedish AT patients in order to study the possible "Swedish phenotype" of the disease. In the 19 patients identified in Sweden we found a phenotype fairly similar to what has been described internationally, with the exception of some differences including lower cancer incidence in patients and their relatives and somewhat more pronounced immunodeficiency and concomitant susceptibility to infections.

Adolescent↗

Imbalanced switch of the IGHG (immunoglobulin constant heavy G chain) Gm(bfn) genes in atopic childhood asthma.

BACKGROUND: The IGHG genes on chromosome 14q32, 5'micron delta gamma3 gamma1alpha1 gamma2 gamma4 epsilon alpha2 3', as studied by Gm allotypes, are involved in the inheritance of atopy. The 5'micron delta b f alpha1 n gamma4 epsilon alpha2 3', Gm(bfn) haplotype of the genetic B1-cell variant has been found to be associated with the atopic phenotype of children with bronchial asthma. METHODS: An indirect competitive enzyme-linked immunosorbent assay for quantitation in serum of the alternative serum Gm allotypes from the gamma3-, gamma1-, and gamma2 loci and radial immunodiffusion for quantitation of IgG subclasses were used. Children with the genetic B1-cell variants B1/B1 (= Gm[bfn/bfn]), B1/B2 (=Gm[bfn/bf-n]), and B1/B4 (=Gm[bfn/ga-n]) and bronchial asthma were investigated and compared to healthy children of the same age and B-cell type. RESULTS: The three groups with B1/B1, B1/B2, and B1/B4 cells exhibited increased IgE. In both homozygous and heterozygous B1 or Gm(bfn), the serum G1m(f) levels from gamma1 loci were significantly downregulated to 75% of normal, while G2m(n) from gamma2 loci were significantly upregulated to about double the normal level. In heterozygous patients with additional B2 or B4 cells, the G2m(-n) levels from gamma2 loci were instead downregulated. G1m(a) from gamma1 of B4 cells was also downregulated. CONCLUSIONS: Children with atopic bronchial asthma demonstrated an imbalanced class switch in rearrangement of the genes for IgG. The activity of G1m(f) from the gamma1 locus was downregulated, but G2m(n) from gamma2 was upregulated together with the closely situated epsilon locus downstream of the IGH genes. Low levels of G1m(f), Glm(a), and G2m(-n) indicated a low pressure of infections. The imbalanced activation of the IGH genes in more hygienic environments might be one explanation of the increased prevalence of atopy in children in recent decades.

Adolescent↗

A human IFNGR1 small deletion hotspot associated with dominant susceptibility to mycobacterial infection.

The immunogenetic basis of severe infections caused by bacille Calmette-Guérin vaccine and environmental mycobacteria in humans remains largely unknown. We describe 18 patients from several generations of 12 unrelated families who were heterozygous for 1 to 5 overlapping IFNGR1 frameshift small deletions and a wild-type IFNGR1 allele. There were 12 independent mutation events at a single mutation site, defining a small deletion hotspot. Neighbouring sequence analysis favours a small deletion model of slipped mispairing events during replication. The mutant alleles encode cell-surface IFNgamma receptors that lack the intra-cytoplasmic domain, which, through a combination of impaired recycling, abrogated signalling and normal binding to IFNgamma exert a dominant-negative effect. We thus report a hotspot for human IFNGR1 small deletions that confer dominant susceptibility to infections caused by poorly virulent mycobacteria.

Adolescent↗

Preparation of IgG subclass allotypes from polyclonal IgG.

Two allotypes have been identified for each of the IgG subclasses IgG1, IgG2 and IgG3. These allotypes are referred to as G1m(a) and G1m(f), G2m(n) and G2m(-n), and G3m(g) and G3m(b). Using a pool of normal human serum and a combination of preparative electrophoresis, DEAE ion-exchange and protein A-Sepharose chromatography, it was possible to separate G1m(f) from G1m(a), G2m(-n) from G2m(n) and G3m(g) from G3m(b). Purification of G2m(-n) molecules is of special interest as no genetic marker has been found to identify this allotype.

Blood Protein Electrophoresis↗

Serum Gm allotype development during childhood.

Gm allotypes are genetic variants of the immunoglobulin heavy G chains (IGHG) of IgG molecules, coded from chromosome 14q32, characterized by differences in amino acid epitopes of the constant heavy G chains and inherited in the Mendelian manner. Gm allotypes have influence on IgG subclass levels, and serum Gm allotype levels have been given for different Gm genotypes in adults. Four hundred and thirty healthy children, aged 1-15 years, were examined for serum Gm allotypes and IgG subclasses from the six most common Gm genotypes and different age groups were measured using competitive enzyme-linked immunosorbant assay and radial immunodiffusion methods. Quantities (in g/l) of G1m(a) and G1m(f) of IgG1, G2m(n) and G2m(-n) of IgG2 and G3m(g), and G3m(b) of IgG3 are given. Different maturation rates of the alternative Gm allotypes within IgG1, IgG2 and IgG3 were shown. G2m(n) development was strikingly retarded compared with G2m(-n) from the gamma2 locus. This was found comparing IgG2 levels from homozygous G2m(-n-n) and G2m(nn) individuals, but was also seen in heterozygous G2m(n-n) genotypes. From the gamma1 locus G1m(f) levels dominated significantly, but inconstantly, over G1m(a) levels in heterozygous G1m(af) individuals. In homozygous G1m genotypes, G1m(aa) compared with G1m(ff) of the same age, one or the other dominated, sometimes significantly. Serum levels of G3m(b) from the gamma3 locus of homozygous G3m(bb) individuals were increased significantly compared with G3m(g) levels of homozygous G3m(gg) individuals, in ages over 3 years. However, in heterozygous G3m(gb) individuals G3m(b) dominance was not evident. There is a relatively rapid development of G1m(f) molecules and a retarded development of G2m(n) in the Gm(f;n;b) haplotype. In comparison, G1m(a) is retarded and G2m(-n) is enhanced in the Gm(a;-n;g) haplotype. The retarded serum G2m(n) development is comparable with serum IgA development during childhood. Different maturation rates of Gm allotypes within the same IgG subclass provide further explanation for the variation of the antibody response during childhood. Quantitative Gm allotype determinations give information of the activity from IGHG genes. The genetic variation constitutes an additional basis for evaluation of IgG antibodies in different diseases in childhood.

Adolescent↗

Alternative G1m, G2m and G3m allotypes of IGHG genes correlate with atopic and nonatopic pathways of immune regulation in children with bronchial asthma.

Most genetic studies of bronchial asthma deal with IgE responsiveness. The manner by which allergens trigger IgE production and activate mast cells suggests that several genetic loci may be involved. Several reports of candidate genes include chromosome 6 and HLA antigens, chromosome 14q11 and the alpha chain of the T cell receptor, chromosome 11q32 and the beta chain of the high-affinity IgE receptor and chromosome 5 and the gene cluster for IL-4, respectively. In addition, the immunoglobulin heavy chain G (IGHG) genes on chromosome 14q32 have been associated with both atopic and non atopic bronchial asthma in children. In order to further investigate the role of IGHG genes in asthmatic children, the phenotypes of patients with homozygous but alternative IGHG genes were investigated. IGHG gene expression of patients with childhood asthma was determined by serum Gm allotypes with a quantitative competitive indirect ELISA method. The groups consisted of 24 children with the homozygous G3m(b/b)-G1m(f/f)-G2m(n/n) and 16 with the alternative G3m(g/g)-G1m(a/a)-G2m(-n/-n) genes. The two different genotypes were investigated for serum IgE (PRIST), serum IgG subclass levels (radial immunodiffusion), Gm allotype levels (competitive ELISA), IgA and IgM levels (radial immunodiffusion), peripheral blood eosinophils, specific IgE antibodies (skin prick test, SPT, or radioallergosorbent test, RAST), number of peripheral blood CD lymphocyte markers (flow cytometry) and serum IL-4 and IFN-gamma levels (ELISA). Comparison of the two genotypes in children with bronchial asthma revealed significantly increased IgE (p < 0.001), increased specific IgE (p < 0.001), as investigated by SPT or RAST (n = 10 allergens tested), increased number of peripheral blood eosinophils (p < 0.01), increased serum IgG1(f/f)(p < 0.001), IgG2(n/n) (p < 0.001) and IgG3(b/b)(p < 0.01) levels, and decreased CD8 given in percent of the total number of peripheral lymphocytes, (p < 0.02) in the G3m(b/b)-G1m(f/f)-G2m(n/n) genotype. The asthmatic children with the G3m(g/g)-G1m(a/a)-G2m(-n/-n) genes instead showed low IgE levels, practically no specific IgE antibodies, a lower number of peripheral blood eosinophils, lower IgG1(a/a), IgG2(-n/-n) and IgG3(g/g) serum levels and higher CD8 lymphocyte numbers. The results show that the IGHG3(b/b)-IGHG1(f/f)-IGHG2(n/n) genes are in linkage disequilibrium with allergen-specific high-responding IGHE genes and present the atopic phenotype of bronchial asthma, while the IGHG3(g/g)-IGHG1(a/a)-IGHG2(-n/-n) genes present the nonatopic phenotype of childhood asthma. The two genotypes with different amino acid epitopes of their constant heavy gamma1, gamma2 and gamma3 chains presented qualitatively different IgG1, IgG2 and IgG3 molecules, respectively, and also different serum IgG1, IgG2 and IgG3 levels, together with different numbers of peripheral blood eosinophils and CD8 lymphocytes. The two IGHG genotypes represent different pathways of human immune regulation. An association of atopic IGHG genotype with other candidate genes for atopy could be suggested.

Adolescent↗

Different Gm allotype amounts in human intravenous immunoglobulin (IVIG) preparations; survival of foreign Gm allotypes in immunodeficient patients.

IVIG is used as standard replacement therapy in primary antibody deficiency. IVIG consists mainly of IgG. IVIG preparations were investigated with respect to Gm allotypes, which are characterized by various amino acid epitopes in the constant heavy chains of the IgG subclasses IgG1, IgG2 and IgG3. The alternative allelic Gm allotypes G1m(a) and G1m(f) of IgG1, G2m(n) and G2m(") of IgG2 and G3m(g) and G3m(b) of IgG3 were measured by sensitive competitive ELISAs for G1m(a), G1m(f), G2m(n) and G3m(b). IgG subclass levels were quantified by radioimmunodiffusion (RID). Gm allotype quantities differed significantly in various IVIG products, with different products having half or double the amount of the different Gm allotypes. The results show the effect of the different manufacturing processes, but also indicate different physicochemical properties of Gm allotypes within the same IgG subclass. The different contents of Gm allotypes might be one reason for the variable levels of specific antibodies found in IVIG products. Immunodeficient patients with homozygous expression of Gm allotypes from IGHCG1, IGHCG2 and IGHCG3 were tested after infusion of foreign Gm allotypes. A prolonged survival was found for the G2m allotype, G2m(n), compared with G1m allotypes. Different half-lives were found for the alternative G1m(a) and G1m(f) allotypes, within the same IgG1 subclass.

Enzyme-Linked Immunosorbent Assay↗

Development of allergy to laboratory animals is associated with particular Gm and HLA genes.

To find out whether IgG genes are involved in atopy we studied 26 of 101 laboratory technicians who had developed laboratory animal allergy (LAA). The genes for the constant region of the heavy chains of IgG subclasses were analyzed by serum Gm allotypes, representing products on allelic level of the IGHCG1, IGHCG2 and IGHCG3 on chromosome 14q32. There was a significantly increased frequency of the GM(f,f;n,n;b,b) genotype (57.7 instead of 22.3%, p < 0.001) representing IgG1, IgG2 and IgG3 molecules and in particular increased frequency of Gm genotypes with the homozygous expression of G2m (n,n) (69.2 instead of 27.4%, p < 0.001) and of the Gm(f,n,b) haplotype (75 instead of 44.8%, p < 0.001) compared to a normal Caucasian population. An increased HLA-DR4 content of the LAA group (61.5 instead of 33.7%, p < 0.01) was further investigated for Gm allotypes. Among 16 HLA-DR4 LAA individuals, the Gm(f,f;n,n;b,b) genotype (56.3 instead of 22.3%, p < 0.01) and the Gm genotypes with the homozygous expression G2m(n,n) (62.6 instead of 27.4%, p < 0.01) dominated. However, the HLA-DR4 frequency among Gm(f,f;n,n;b,b) of LAA patients did not deviate from the frequency of healthy individuals of the same Gm genotype. The increased frequency of HLA-DR4 antigen in LAA patients might be due to its association to the Gm(f,f;n,n;b,b) genotype. This study supports the following concept: the susceptibility of developing LAA is associated with Gm allotypes Glm(f) expressed from IGHCG1, G2m(n) from IGHCG2 and G3m(b) from IGHCG3 on both alleles situated close to IGHCE on chromosome 14q32. The association of LAA to Gm allotypes [Gm(f,f;n,n;b,b)] expressed from chromosome 14q32 and of HLA class II antigens (HLA-DR4) expressed from chromosome 6p21.3 further confirms the polygenic inheritance of the immune response in atopy.

Animals↗

Suppressed G2m(n) levels from IGHCG2 in IgA deficiency.

The aim of the study was to investigate the production of IgG from alternative alleles of IGHCG1, IGHCG2 and IGHCG3, closely related to IGHCA1 and IGHCA2 on chromosome 14, in IgA deficient (IgAD; serum IgA levels < 0.05 g/l) for individuals. Sixty-two IgAD individuals were included in the study and sera were investigated with the sensitive competitive indirect ELISA for measuring serum concentrations of the Gm allotypes G1m(a), G1m(f), G2m(n) and G3m(b), performed with specific monoclonal antisera and purified myeloma proteins in combination with IgG subclass quantitation. The known 'compensatorily increased' serum levels of IgG1 and IgG3 were recognized with significantly increased G1m(a) and G1m(f) from IGHCG1 and significantly increased G1m(g) and G3m(b) from IGHCG3. The quotients of G1m(a)/G1m(f) from IGHCG1 and G3m(g)/G3m(b) from IGHCG3 were also normal. Instead, the levels of G2m(n) from IGHCG2 were selectively decreased in combination with normal or increased levels of G2m(") from the same IGHCG2. The quotient G2m(n)/G2m(") was also significantly decreased. As the selectively decreased G2m(n) allotype expression from IGHCG2 was situated close to the non-expressing IGHCA1, the origin of most serum IgA could be the result of a defective common regulating factor. The selectively decreased G2m(n) allotype levels from IGHCG2 must also be discussed with a view to Gm allotype suppression described in mice. The selectively decreased G2m(n) allotype levels in G2m(n,") heterozygous IgAD individuals could be the result of a preferential allelic exclusion of G2m(n) favoring G2m(") on IGHCG2 in many cells.

Alleles↗

Serum Gm allotype levels in common variable immunodeficiency: preponderance of homozygous G2m(",") on IGHCG2.

Common variable immunodeficiency (CVI) is one of the most frequent primary immunodeficiency diseases, characterized by defective antibody formation and associated with chronic sinopulmonary infections, autoimmunity and malignancies. The genes for the constant heavy chains of IgG are located on chromosome 14 and were further studied by identifying allelic, alternative Gm allotypes. These were defined by different epitopes for three of the IgG subclasses, G1m(a) and G1m(f) for IgG1, G2m(n) and G2m(") for IgG2 and G3m(g) and G3m(b) for IgG3. A sensitive competitive ELISA method for quantitation of the Gm allotypes G1m(a), G1m(f), G2m(n) and G3m(b) were used together with radial immunodiffusion IgG subclass quantitation. The dominating number of 25 of 33 patients (p < 0.001) expressed the homozygous G2m(",") allotype on IGHCG2 in combination with homozygous or heterozygous Gm allotypes on IGHCG1 and IGHCG3, namely Gm(f,f;",";b,b), Gm(a,a;",";g,g) and Gm(f,a;",";b,g). Studies of Gm allotype quantities revealed a progressive sequential impediment of the programmed cascade for downstream IGHCG gene rearrangements. According to the order of the IGHCG genes, the G3m allotype levels from the IGHCG3 were often normal, and G1m allotype levels from IGHCG1 were suppressed; G1m(a) was suppressed more than G1m(f), and most suppressed were G2m allotype levels from IGHCG2, both G2m(n) and G2m("). The susceptibility of CVI is associated to G2m(",") expression from the IGHCG2 locus on chromosome 14, which has also been found in IgA IgG subclass deficiency, conditions known among first-degree relatives.

Adult↗

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↗

Analysis of immunoglobulin isotype levels in acute pneumococcal bacteremia and in convalescence.

In 48 patients with a history of a pneumococcal bacteremia, serum taken during the acute phase of the infection was analyzed for IgG and IgG subclasses. Once the patients were free of infection, a serum sample was analyzed for IgG, IgG subclasses, IgA and IgM. In an additional 20 patients, it was only possible to analyze serum from the infection-free phase. Seventeen of 48 (35%) patients had reduced levels of total IgG or of one or more of the IgG subclasses during acute disease. Of the 48 patients in whom both acute phase and infection-free phase serum were analyzed, values of IgG (p < 0.001), IgG1 (p < 0.001), IgG2 (p < 0.001), IgG3 (p < 0.01) and IgG4 (p < 0.01) were decreased during the acute infection. During the infection-free phase, 12 of 68 (18%) patients had a recognizable immunodeficiency, including two patients with common variable immunodeficiency. Routine screening for immunoglobulins during the infection-free period could result in the discovery of previously unrecognized immunoglobulin deficiencies in patients with a history of bacteremic pneumococcal infection.

Acute Disease↗

The importance of G1m and 2 allotypes for the IgG2 antibody levels and avidity against pneumococcal polysaccharide type 1 within mono- and dizygotic twin-pairs.

Eighty-two mono- or dizygotic Caucasian twins vaccinated with a 23-valent pneumococcal vaccine, who had previously had their IgG2 antibody levels to pneumococcus type 1 determined before and after vaccination, were included in this study. Their IgG2 antibody levels were related to their G1m and G2m allotypes/phenotypes and their Gm amounts. Eight different Gm phenotypes were found and characteristically IgG2 antibody levels were related to them. G2m (n) homozygotic twins had significantly higher IgG2 levels than heterozygotic twins who had significantly higher levels than G2m (-n) homozygotic twins (P < 0.05). The G1m allotype, on the other hand was without influence on the IgG2 levels and so were the Gm amounts among G2m (n) heterozygotic twins. The IgG2 antibody avidities were not related to Gm allotypes but significantly correlated to IgG2 levels (P = 0.05). Finally, a highly significant intra-pair correlation was found for avidity in the monozygotic twins supporting a genetic regulation of avidity (P < 0.002). These results may explain our earlier findings that IgG2 antibody levels after pneumococcal vaccination are significantly more closely correlated within mono- compared to dizygotic twins.

Adult↗

Quantitation of Gm allotypes.

A method for quantitation of Gm allotypes is described. Alternative Gm allotypes of the three IgG subclasses, IgG1, IgG2 and IgG3, were investigated for the six most common Caucasian Gm phenotypes. Quantitation of G1m(a), G1m(f) of IgG1, G2m(n) of IgG2 and G3m(b) of IgG3 was performed with specific monoclonal antisera and purified myeloma proteins of different Gm allotypes. Mean +/- SD are given as percentage of a normal serum pool and in g/l for the Gm allotypes G1m(a), G1m(f), G2m(n) and G3m(b). For homozygous individuals the G2m(",") values are equal to the IgG2 levels and the G3m(g,g) values equal to the IgG3 levels. For heterozygous individuals the value for G2m(") is calculated as IgG2 minus G2m(n) and for G3m(g) as IgG3 minus G3m(b). Homozygous individuals have about double the amounts of the Gm allotype compared with heterozygous individuals. The gene activity of heterozygous individuals is given by quotients, mean +/- SD for G1m(a)/G1m(f) of IgG1, G2m(n)/G2m(") of IgG2 and G3m(b)/G3m(g) of IgG3 in different Gm phenotypes. Heterozygous individuals on all three IgG subclass loci have at least six different qualities of IgG molecules compared with three for homozygous individuals.

Blood Donors↗

Serum IgG and IgG subclass contents in different Gm phenotypes.

Different serum IgG and IgG subclass levels were found among Gm phenotypes of a normal population. One hundred and fifty-seven Caucasian blood donors were investigated for the reciprocal Gm allotypes on IgG subclass loci namely: for IgG1, G1m(f) and G1m(a); for IgG2, G2m(n) and G2m("); and for IgG3, G3m(b) and G3m(g), and subgrouped in the seven most common Gm phenotypes. The frequencies of Gm phenotypes and haplotypes were given, including numbers of the previously little known G2m(n,") heterozygous individuals. Mean serum quantities +/- SD and range of IgG, IgG1, IgG2, IgG3 and IgG4 were given for different Gm phenotypes. The IgG content was significantly lower in the Gm(f,",b/f,",b) phenotype in which the IgG2 levels were also significantly lower, compared with values of the other phenotypes. IgG3 levels were significantly lower in the Gm(a,",g/a,",g) phenotype compared with other phenotypes. These data imply the importance of Gm(f,",b/f,",b) and Gm(a,",g/a,",g) phenotypes causing lower amounts of IgG antibodies. In evaluating IgG subclass deficiency, the range for the low responding Gm(f,",b/f,",b) and Gm(a,",g/a,",g) phenotypes should be considered.

Blood Donors↗

Gm allotypes as indicators of non-atopic and atopic bronchial asthma.

69 Caucasian children, 34 with non-atopic and 35 with atopic bronchial asthma, demonstrated different, Gm-associated IgG antibody responsiveness. The non-atopic bronchial asthma group showed a preponderance of the Gm(a,'',g) haplotype, while the atopic study group showed a preponderance of the haplotype with the alternative allotypes on all IgG subclass loci, namely Gm(f,n,b). Patients with non-atopic bronchial asthma showed a significantly increased frequency of the phenotypes containing the Gm(a,'',g) haplotype, namely the Gm(a,'',g/a,'',g) and Gm(a,'',g/f,'',b), and an increased number of individuals were homozygous G2m('','') on the IgG2 locus. The 2 asthma groups showed different characteristic IgG subclass patterns, the non-atopic group with significantly decreased IgG2 and IgG3, especially those of the Gm(a,'',g/a,'',g) phenotype, and the atopic group with significantly increased IgG1 and IgG4, especially those of the Gm(f,n,b/f,n,b) phenotype. The characteristic IgG subclass patterns originate from the different Gm phenotypes found in the 2 groups. The results emphasize the presence of qualitatively and quantitatively different IgG molecules in non-atopic and atopic bronchial asthma patients and show the interest in studying IgG genes and IgG molecules as markers of pathogenesis. G2m('','') homozygosity is a new important marker of non-atopic bronchial asthma.

Adolescent↗