Immunoglobulin allotypes in patients with nasopharyngeal carcinoma

Gm phenotypes and the Km(1) allotype were studied in Tunisian patients with nasopharyngeal carcinoma (NPC). A highly significant association was found between the Km(1) allotype and the NPC disease. Two rare Gm haplotypes, Gm(1, 17; 11, 15, 21) and Gm(1, 3, 5, 11), were found to be significantly increased among the NPC patients.     

Gm and Km frequencies in a Portugese population

Summary Serum samples from 79 healthy subjects and 31 patients with type I amyloid neuropathy were typed for nine Gm markers. No significant associations were found between any of the Gm phenotypes and the disease. The frequencies of the various phenotypes showed satisfactory agreement with the Hardy-Weinberg distribution. One individual had an unusual Gm phenotype.Publication no. 526 from the Department of Basic and Clinical Immunology and Microbiology, Medical University of South Carolina. Research supported in part by USPHS Grants CA-25746 and AI-07063, and by South Carolina State Appropriations for Research     

Gm and Inv allotypes in a Gypsy sample.

Serum samples from 226 Gypsies were tested for Gm(1,2,4,5,8,10,11,14,17,21,23,25) and for Inv(1,2). The Gm phenotypes found are very numerous and the more frequent among this population are: Gm(4,5, 8,10,11,14,17,23,25) and Gm(1,2,4,5,8,10,11,14,17,21,23,25). All the phenotypes except three can be explained by nine haplotypes: Gm4,5,8,10,11,14,23,25, Gm1,4,5,8,10,11,14,23,25, Gm4,5,8,10,11,14,25, Gm1,17,21, Gm1,10,11,17,25, Gm1,2,17,21, Gm1,8,17,21, Gm1,8,17,21,23 and Gm1,5,10,11,14,17. The haplotypes Gm1,17,21, Gm1,2,17,21, Gm4,5,8,10,11,14,25 (with or without Gm[ 3]) are all three common among Caucasoids, Gm1,4,5,10,11,14,23,25 (common among Mongoloids) and Gm1,5,10,11,14,17 (common to Negroids). For the Inv system, this population possesses a very low frequency of Inv(1) and Inv(2).     

Gm and Inv allotypes of some Sidamo Ethiopians

One hundred and forty serum samples from Ethiopians from three tribes of the Sidamo group were tested for their Gm and Inv phenotypes. The Gm antigens 1,2,3,5,6,13,14,21 were determined on all samples, and Gm(15) and Gm(16) were determined on selected samples. All samples were tested for Inv(1), and those positive for Inv(1) were tested for Inv(3). The samples fall into 18 Gm phenotypes and require seven haplotypes to explain them. The data indicate that these Ethiopians have Negroid, Caucasoid, and Bushmanoid ancestry, with the latter constituting a relatively small proportion of the ancestry and the former two contributing about equally to the remainder. The data are consistent with the conclusions of cultural anthropologists.     

On the incidence of blood group O and Gm(−1) phenotypes in patients with malignant melanoma

Summary Fifteen polymorphic systems of the blood (ABO, MNSs, Rhesus, P, Kell, Duffy, Kidd, Hp, Gc, Gm, Inv, aP, PGM₁, EsD, and 6-PGD) were examined in 191 unrelated male and female patients suffering from malignant melanoma. These polymorphic systems were compared with the corresponding phenotype and gene frequencies of controls from the same geographical area (Rhineland-Palatinate). The only associations discovered were the ABO and Gm polymorphisms: The incidence of O and Gm(-1) phenotypes in patients is obviously higher than in controls. These observations agree with the findings in other population samples from Germany and Bulgaria.     

Gm and Inv allotypes in French Guiana Indians.

Data from 302 individuals belonging to three populations of French Guiana Indians are reported. All the phenotypes except two can be explained by three haplotypes: Gm1,21, Gm1,2,21 and Gm1,10,11,25. The gene frequencies found in the present study are generally in accordance with those previously described among other South American Indians. For the Inv1,2 gene a high value has been found for the Wayanas and the Oyampis, but a difference appears for the Emerillons who possess a low frequency.     

Distribution of Gm and Km allotypes among five populations in China

Serum samples from five populations in China [173 from Huhehote (Naimengu Zhizhiqu), 195 from the Beijing area, 131 from Hefei (Anhui Province), 155 from Hangzhou (Zhejiang Province), and 152 from Guangzhou (Guangdong Province)] were tested for G1m(1, 2, 3, and 17), G2m(23), G3m(5, 10, 11, 13, 14, 15, 16, 21, and 26), and Km(1). The Gm pattern of the Chinese populations are characterized by the presence of four haplotypes, Gm1, 17;..;21, 26, Gm1, 2, 17;..;21, 26, Gm1, 17;..;10, 11, 13, 15, 16, and Gm1, 3;23;5, 10, 11, 13, 14, 26, which are characteristic of Mongoloid populations. Agreement was obtained in all Chinese samples between the observed and expected frequencies on the basis of the Hardy-Weinberg equilibrium of phenotypes. Heterogeneity tests of the haplotypic distributions among the five populations showed no significant differences in the distributions of Gm phenotypes between Huhehote and Beijing nor between Hefei and Hangzhou, whereas highly significant differences were observed among the three districts: northern part (Huhehote and Beijing), central part (Hefei and Hangzhou), and southern part (Guangzhou). The data indicate a south to north genocline, ranging from Huhehote to Guangzhou in which Gm1, 17;..;21, 26 changes from 0.471 to 0.183, Gm1, 17;..;10, 11, 13, 15, 16 from 0.097 to 0.033, and Gm1, 3;23;5, 10, 11, 13, 14, 26 from 0.229 to 0.730. In contrast to the Gm system, no significant regional differences in the frequencies of the Km1 allele were observed among the five populations.     

Heteroclitic polyclonal and monoclonal anti-Gm(a) and anti-Gm(g) human rheumatoid factors react with epitopes induced in Gm(a-), Gm(g-) IgG by interaction with antigen or by nonspecific aggregation. A possible mechanism for the in vivo generation of rheumatoid factors.

Heteroclitic rheumatoid factors (RF) are specific for allotypic determinants, e.g., Gm(a) or Gm(g) on allogeneic, but not autologous IgG. All polyclonal RF we isolated from nine rheumatoid arthritis patients with circulating Gm(a-), (b+), (g-), (f+) IgG displayed dual heteroclitic activity for the Gm(a) and Gm(g) allotypes, as shown by using appropriate RBC agglutination assays and affinity columns bearing Gm(a+) or Gm(g+) IgG. To investigate possible mechanisms underlying the in vivo generation of heteroclitic RF, we tested the ability of nonspecifically and immune-specifically aggregated Gm(a-), (g-) IgG to function as targets for RF from Gm(a-), (g-) patients with rheumatoid arthritis. Heat aggregation (63 degrees C for 20 min) or binding to Ag (as in tetanus toxoid-antitetanus toxoid complexes) induced a "functional" Gm(a+) and/or (g+) phenotype in Gm(a-), (g-) IgG from five healthy subjects and five rheumatoid patients, as suggested by the ability of these altered IgG to function as efficient targets for six heteroclitic RF in direct binding and competitive inhibition experiments. That heterocliticity and dual Gm(a), Gm(g) specificity can be features of a single antibody molecule was formally demonstrated by analysis of a monoclonal RF (IgM mAb 61) generated from a Gm(a-), (g-) rheumatoid patient. RF mAb 61 displayed a high affinity (Kd, 10(-7) M) for IgG Fc fragment of Gm(a+) and (g+) IgG or aggregated autologous Gm(a-), (g-) IgG but did not bind to native autologous IgG. To investigate the molecular basis of the acquired Gm(a) phenotype, PBMC from five Gm(a-) patients with rheumatoid arthritis and two Gm(a-) normal subjects arthritis and two Gm(a-) normal subjects were cultured in vitro after activation with PWM. In most instances, these PBMC produced IgG that behaved as Gm(a+) in sensitive ELISA. Application of the polymerase chain reaction (PCR), using probes specific for the nucleotide sequence coding for the Gm(a) tetrapeptide, to the amplification of DNA from the in vitro-stimulated Gm(a-) normals or rheumatoid patients' PBMC provided no evidence for Gm(a) nucleotide sequences. The present data suggest that acquisition of the Gm(a) determinant by Gm(a-) IgG may result from subtle changes in the CH2-CH3 RF-binding region. Such changes would occur when Gm(a) IgG are complexed with Ag or nonspecifically altered, thereby providing a possible explanation for the induction of heteroclitic RF in Gm(a-) rheumatoid arthritis patients.     

Serum Gm system in liver cirrhosis and hepatoma

Summary Serum Gm polymorphism was studied in 69 patients with liver cirrhosis, in 64 with liver cirrhosis plus hepatoma, in 40 with hepatoma without evidence of cirrhosis, and in 256 controls. The distribution of Gm factors in liver patients differed from that in the control group, this difference apparently being due to the distribution in cirrhosis patients negative for HBsAg and anti-HBs. Furthermore, significantly more heterozygous Gm individuals were found in this group of patients than in the control group. Thus it appears that Gm heterozygous individuals are prone to develop cryptogenic cirrhosis under the influence of other, as yet undetermined factors.     

Imbalance in recruitment of IgG (Gm) allotype-producing B-cell subsets from blood to brain in multiple sclerosis

In Gm3/Gm3 homozygous multiple sclerosis (MS) patients, in vitro production of the G1m(3) allotype of IgG1 induced by the T-independent polyclonal B-cell activator Salmonella paratyphi B (SPB) was lower than that of normal individuals of the same Gm phenotype. In contrast, lymphocytes from Gm1/Gm3 heterozygous MS patients responded to the same stimulus with a significantly increased G1m(3) allotype synthesis not observed in normal individuals of the same phenotype. The high level of intrathecal IgG1 production observed in MS patients might be achieved by a selection at the blood-brain barrier of some peripheral T-independent B-cell clones which in Gm3/Gm3 homozygous would bear the G1m(3) allotype, hence a peripheral depletion of this subset, whereas in Gm1/Gm3 heterozygous a preferential admission of the G1m(1)-producing B-cells would lead to a preferential synthesis of this allotype in the central nervous system and to a relative increase of G1m(3) production by the remaining peripheral B cells.     

Association between immunoglobulin allotypes and pulmonary tuberculosis

In a sample of n = 133 non-related patients suffering from pulmonary tuberculosis, Gm and Km typings have been carried out and compared with healthy controls from the same geographical area. All the Gm allotypes tested were found to be more preponderant in the patients than in the healthy controls and these differences were found to be statistically significant for Gm (1) and Gm (5) only and not for the other immunoglobulin allotypes e.g. Gm (2). The frequency of Km (1) was lower and that of Km (3) was higher in the patients than in the controls. These differences were, however, statistically not significant.     

Gm and Inv studies on baboons, Papio cynocephalus: analysis of serum samples from Kenya, Ethiopia and South Africa.

Serum samples from 526 baboons (Papio cynocephalus) from 10 troops from the Laikipia district of northern Kenya, from 60 baboons from two troops from the Awash National Park, central Ethiopia, and from 127 baboons from South Africa were tested for Gm and Inv allotypes. Four of the 10 troops from Kenya formed a western cluster and six formed an eastern cluster. The clusters were separated by approximately 10 miles. The samples were tested for Gm (1, 2, 3, 5, 6, 11, 13, 14, 15, 16, 17, 21, 24) and for Inv (1, 2, 3). All samples were negative for Gm (2, 6, 14, 16, 24). All from Kenya and Ethiopia were negative for Inv (2), and all were positive for Gm (11, 17) and for Inv (3). The south African samples differed from the others in that 10 were negative for Gm (11) and four were positive for Inv (2). Taking all animals into account, polymorphism was present for Gm (1, 3, 5, 11, 13, 15, 21) and for Inv (1, 2). No two Kenya troops had the same array of phenotypes or of haplotypes, but the four western troops were more similar to each other than to the six eastern troops. Three haplotypes were present in the eastern troops that were not present in the western troops and five were present in the western troops that were not present in the eastern troops. Five haplotypes appeared in at least some troops of each cluster of troops. The samples from each of the two troops from Ethiopia show the same three phenotypes but with significantly different frequencies. It is suggested that the variation in haplotype frequencies observed among the 10 troops from Kenya is the result of a founder effect deriving largely from fission of a large troop into two smaller troops. The data show that speculations about the evolutionary origin of the allotypes are premature. For most species, too few animals have been tested and except for those in this study their origins are not known. Finally, the samples have been from too restricted an area.     

Gm(1) and Gm(2) immunoglobulin allotypes in patients with malignant melanoma.

Gm allotype markers were determined in sera from 71 melanoma patients and 400 control persons. There was no significant difference between both groups in Gm distribution. The results were compared to a recent report. Furthermore, in 25 malanoma patients the capacity of serum to interfere with cell-mediated cytotoxicity (CMC) of autologous lymphocytes was determined and related to the Gm allotype.     

Serumprotein polymorphisms in Iran

Summary The results of a population genetic investigation on Iranians are given and compared to the results obtained on other populations from Southwestern and Southern Asia. Our total material from Iran comprises n=1020 nonrelated male and female individuals of different age. The following serum groups have been typed: Hp, Gc, Gm, and Inv. In general there exist no remarkable age or sex differences in the distribution of phenotypes and alleles (the only exception: sex differences in the distribution of the Gm (7)-phenotype). The regional distribution of phenotypes and alleles yield no marked differences, too, apart from the Invphenotypes, however. For the total material of Iran the following alleles frequencies could be calculated: Hp¹=0.3045, Hp²=0.6595, Gc²=0.3405; Gm¹=0.1780, Gm^1,2=0.0537, Gm^1,5=0.0632, Gm⁵=0.7051. The Gm (7)-phenotype turned out to be 36.6%; the Inv (1)-phenotype amounts to 25.6%. Comparing with other populations, especially Pakistani and Indian samples, some heterogeneity in the distribution of phenotypes and alleles within Southwestern and Southern Asia was to be demonstrated. Some distributional trends of alleles frequencies shall be mentioned here: the increase of Hp², Gc¹, and Gm¹ alleles from West towards East, and in the opposite direction the decrease of Hp¹, Gc², and Gm⁵ alleles. Selective acting forces are supposed to be most important factors for this. D77     

Gammaglobulin groups of the Khoisan peoples of Southern Africa: evidence for polymorphism for a Gm1,5,13,14,21 haplotype among the San.

The Gm and Inv types were determined for eight San (Bushman) populations, two Khoikhoi (Hottentot) populations, one Coloured population, 112 San families in which the genotypes of the parents could be unambiguously determined, and for 65 San families in which the genotype of one or both parents could not be determined with certainty. The population and family data establish that the haplotype array of the San is composed of Gm1,21, Gm1,13, Gm1,5,13,14, and Gm1,5,13,14,21; Gm1,5,6 and Gm1,5,6,14 are also present but may have been acquired through admixture with Negroes. The Gm1,5,13,14,21 haplotype has not been found to be polymorphic in any other population. The haplotype array of the Khoikhoi is composed of Gm1,2,21, Gm1,13, and Gm1,5,13,14; Gm1,5,6 and Gm1,5,6,14 are also present but, as in the case of the San, may be due to admixture. The San and Khoikhoi differ from each other in that the former have the Gm1,21 and Gm1,5,13,14,21 haplotypes not present in the latter, and the Khoikhoi have the Gm1,2,21 haplotype not present in the San. These three haplotypes and Gm1,13 serve to distinguish the Khoisan people from other African peoples.     

Tagging and mapping of a rice gall midge resistance gene, <Emphasis Type="Italic">Gm8</Emphasis>, and development of SCARs for use in marker-aided selection and gene pyramiding

Using amplified fragment length polymorphisms (AFLPs) and random amplified polymorphic DNAs (RAPDs), we have tagged and mapped Gm8, a gene conferring resistance to the rice gall midge (Orseolia oryzae), a major insect pest of rice, onto rice chromosome 8. Using AFLPs, two fragments, AR257 and AS168, were identified that were linked to the resistant and susceptible phenotypes, respectively. Another resistant phenotype-specific marker, AP19₅₈₇, was also identified using RAPDs. SCAR primers based on the sequence of the fragments AR257 and AS168 failed to reveal polymorphism between the resistant and the susceptible parents. However, PCR using primers based on the regions flanking AR257 revealed polymorphism that was phenotype-specific. In contrast, PCR carried out using primers flanking the susceptible phenotype-associated fragment AS168 produced a monomorphic fragment. Restriction digestion of these monomorphic fragments revealed polymorphism between the susceptible and resistant parents. Nucleotide BLAST searches revealed that the three fragments show strong homology to rice PAC and BAC clones that formed a contig representing the short arm of chromosome 8. PCR amplification using the above-mentioned primers on a larger population, derived from a cross between two indica rice varieties, Jhitpiti (resistant parent) and TN1 (susceptible parent), showed that there is a tight linkage between the markers and the Gm8 locus. These markers, therefore, have potential for use in marker-aided selection and pyramiding of Gm8 along with other previously tagged gall midge resistance genes [Gm2, Gm4(t), and Gm7].The nucleotide sequence data reported here will appear in the EMBL, GenBank and DDBJ nucleotide sequence databases under the accession numbers AY545920–AY545923     

Screening of the Philadelphia variant of galactokinase in racially unmixed black Africans: first results.

In previous reports, it was emphasized that the gene GALKA of galactokinase was the predominant allele in white populations and that another allele, GALKP, which reduces red blood cell activity (RBC GALK), was common in black people. In a group of black Americans living in Philadelphia, the frequency of GALKA was found to be very close to values expected from independent estimation of white admixture. The authors have suggested that the ancestors of these blacks might have been virtually all GALKP homozygous. We have looked for carriers of GALKP genotypes among 73 black Africans; only 33 probands were shown to have a low RBC GALK. To detect white admixture, immunoglobulin allotypes Km and Gm were investigated in 50 individuals of the sample; 15 GALKP carriers with low RBC GALK and 30 of 35 individuals with normal RBC GALK shared Gm phenotypes exclusive to blacks. Our work demonstrates for the first time the polymorphism of GALK in black Africans in the absence of white admixture.     

Identification and mapping of an AFLP marker linked to Gm7, a gall midge resistance gene and its conversion to a SCAR marker for its utility in marker aided selection in rice

We have identified an AFLP marker SA598 that is linked to Gm7, a gene conferring resistance to biotypes 1, 2 and 4 of the gall midge ( Orseolia oryzae), a major dipteran pest of rice. A set of PCR primers specific to an RFLP marker, previously identified to be linked to another gall midge resistance gene Gm2, also amplified a 1.5-kb (F8LB) fragment that is linked to Gm7. Gm7 is a dominant gene and non-allelic to Gm2. Hybridization experiments with clones from a YAC library of Nipponbare, a japonica variety, a BAC library of IR-BB21, an indica variety, and cosmid clones encompassing Gm2 from Phalguna, an indica variety, with F8LB and SA598 as probes, revealed that Gm7 is tightly linked to Gm2 and is located on chromosome 4 of rice. SA598 was sequenced and the sequence information was used to design sequence-characterized amplified region (SCAR) primers. The potential use of these SCAR primers in marker-aided selection of Gm7 in a rice breeding program has been demonstrated.     

Synthesis of Gm allotypes by human tonsillar lymphocytes in culture: concordance with serum phenotype.

Isolated human tonsillar lymphocytes were cultured with pokeweed mitogen, phytohemagglutinin, and without mitogen for 9 to 28 days. IgK, Gm(a) and Gm(f) were then quantitated in the cell suspensions. In cultures of cells derived from persons whose blood was heterozygous for IgGl allotype antigens Gm(a+f+), approximately equal amounts of Gm(a) and Gm(f) were found. In cultures of cells of Gma or Gmf homozygotes, there was complete concordance between the Gm allotype antigens produced by the cultures and the donor's serum phenotype-with no instance, either at zero time or at culture termination in which a Gm antigen was detected which was absent from the donor's serum. It was concluded that in vitro genetic allotype synthesis in tonsillar lymphocytes during short-term culture mirrored accurately in vivo Gm expression. IgK and Gm antigen synthesis was highest in the flasks containing pokeweed mitogen although both phytohemagglutinin and no-mitogen control flasks showed, in certain experiments, proliferation and an increase in the Ig per viable cell. It was observed that no-mitogen flasks contained twice as much allotype antigen as did phytohemagglutinin flasks suggesting an inhibition of Ig synthesis associated with the mitogen. The tonsillar lymphocytes, under the experimental conditions employed, were shown by a radio-incorporation and immunoprecipitation technique to be synthesizing polyclonal Ig de novo, at the termination of the cultures.