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L K Gaur

Publications and source records attributed to L K Gaur.

33 records · Page 2Linked to original sources
PubMed1996

HLA-DQB1*0201/0302 is associated with severe retinopathy in patients with IDDM.

Some insulin-dependent diabetic (IDDM) patients develop severe forms of retinopathy. Putative risk factors such as hypertension, poor metabolic control, nephropathy and growth hormone levels do not fully explain the progress of retinopathy in these patients. It has been discussed whether there is a genetic marker, since some diabetic patients without any known predisposing risk factors develop severe retinopathy and others do not. In the present study, HLA-DR and DQ were compared in two patient groups with IDDM. One group consisted of patients with early-onset diabetes, with severe non-proliferative or proliferative retinopathy; the other group had no or only mild signs of retinopathy. High resolution HLA typing was carried out by polymerase chain reaction (PCR) and hybridization with allele specific probes. Alleles on the DR3-DQ2 haplotype, DRB1*0301, DQA1*0501 and DQB1*0201, were more frequent in patients with severe retinopathy. A difference was seen when combining certain alleles in the genotypes of DQA1*03/0501 (p > 0.05) and DQB1*0201/0302 (p < 0.01). The findings of the present study suggest that DQB1*0201/0302 is the strongest genetic marker for severe retinopathy and DRB1*0301/0401 only has a secondary influence when combined with this genotype. It seems as if IDDM patients who are positive for the genotype DR3-DQ2/DR4-DQ8 (DRB1*0301-DQA1*0501-DQB1*0201/DRB1*0401 -DQA1*03-DQB1*0302) are at greater risk of developing severe retinopathy.

Adult↗
PubMed1995

Genetic and immunological markers of insulin dependent diabetes in Black Americans.

ICA and GAD65 autoantibody profiles and HLA-DR and DQ analysis were performed on 43 Black juvenile onset IDDM patients and 34 unrelated Black controls from Tennessee, USA. 75% of patients were positive for GAD65 autoantibodies but only 53% had ICA; 39% both ICA and GAD65 antibodies. The strongest HLA association was with the DR3 haplotype DRB1*03 DQA1*0501 DQB1*0201 (63% of patients v 12% of controls RR = 13.0, p < 0.00002). DRB1*04 DQA1*0301 DQB1*0302, associated with IDDM in Caucasians but rare in Negroids, occurred in 27% of patients and 6% of controls (RR = 5.9, p < 0.04). All patients carried DQB1*0302 or DQB1*0201. DQB1*0602 was significantly reduced in patients (2.4% v 41%, RR = 0.036, p < 0.008) and DRB1*1501 was absent in patients (0% v 35%). The frequency of GAD65 autoantibodies in Black American IDDM patients is comparable to that in Caucasians; however ICA positivity is reduced. GAD65 antibodies may therefore be a more sensitive serological test to identify individuals in the Black American general population for markers associated with increased risk of developing IDDM. Current screening methods for predicting preclinical IDDM in Caucasians relies on a combination of immune and HLA markers of IDDM; studies of these markers in the Black Americans will make it possible to extend these options to additional genetically diverse populations.

Adolescent↗
PubMed1994

Increased usage of V beta 2 and V beta 6 in rheumatoid synovial fluid T cells.

OBJECTIVE: To determine if the T cell antigen receptor V beta usage of unstimulated rheumatoid arthritis (RA) synovial fluid (SF) T cells is biased compared with those in peripheral blood (PB). METHODS: Freshly isolated, matched synovial fluid and peripheral blood T cells were analyzed for V beta gene expression using quantitative polymerase chain reaction (PCR) methods. Ten synovial fluid samples from the knees of 7 patients with RA were studied. The PCR assay used 26 V beta primers with a constant region C beta primer, and 2 C alpha primers that co-amplified a product that served as an internal standard. Cycle number and complementary DNA content were controlled to ensure the linear accumulation of PCR products. Labeled products were separated on 10% polyacrylamide gels and counted with a Betascope blot analyzer. RESULTS: There were consistent differences between the V beta gene usage of SF and PB T cells directly isolated from patients with RA, regardless of HLA-DR haplotype. In all synovial specimens, V beta 2 was increased relative to the peripheral blood, while V beta 13.1 and V beta 13.2 were decreased. V beta 6 and V beta 21 were increased in 9 of the 10 synovial samples. Analyses of bilateral SF specimens from 2 subjects and serial specimens from the same knee of 1 subject revealed virtually identical patterns in each patient. The SF V beta bias was not solely due to differences in the proportion of CD4+ and CD8+ cells, because the CD4:CD8 ratios in SF and PB were similar. However, V beta gene usage of separated CD4+ and CD8+ synovial T cells showed that V beta 2 and V beta 6 were more highly expressed on CD4 cells. CONCLUSION: Freshly isolated synovial T cells from inflamed (not end-stage) knees of patients with RA have a remarkably consistent biased V beta gene usage compared with PB T cells. V beta 2 and V beta 6 are uniformly increased, and this increase is primarily in CD4+ T cells. The same V beta bias in the SF T cells of several RA patients suggests that shared antigens may be stimulating the T cell response.

Adult↗
PubMed1994

Prosimian MHC-DQB allelic polymorphisms.

In this report the first description of MHC-DQB homologues in prosimians, the lemurs (Lemur fulvus sanfordi) and galagos (Galago garnetti and G. senegalensis moholi), is presented. In these species the class II alleles are similar to their human counterparts, in that the number and position of substitutions are analogous to the substitutions among various human DQB alleles. Presence of allelic variants for both DQB1 and DQB2 in all three species of prosimians studied suggests that the divergence of DQB1-DQB2 allelic lineages predates the divergence of human and prosimian lineages. The DQB2-like sequences from both species of the Galago seem more distant to human DQB2, and somewhat distant to that of the lemur DQB2 and bear numerous species-specific substitutions. It is not clear whether these DQB2-like alleles belong to a third DQB locus or are a true homologue of the contemporary HLA-DQB2 locus.

Alleles↗
PubMed1992

Conservation of the HLA-DQB2 locus in nonhuman primates.

The evolutionary history of MHC class II genes is characterized by several examples of gene duplication, leading both to the creation of distinct subregions such as DR, DQ, and DP, as well as to duplicated loci within each of these subregions. In the human MHC, a prominent example of this diversification occurs within the HLA-DQ subregion, where the nonpolymorphic and transcriptionally "silent" DQB2 locus is highly homologous to the polymorphic expressed DQB1 locus. In order to gain some insight into the mechanisms constraining polymorphism at the DQB2 locus, the second exons of five nonhuman primate DQB2 alleles were sequenced. Six nonhuman primate DQB2 analogous sequences were obtained, two each from chimpanzee and owl monkey cell lines, and one each from gorilla and gibbon cell lines. Notably, the DQB2 sequences from the gibbon, gorilla, and one of the two chimpanzee sequences, although containing some silent nucleotide changes, encode a predicted DQB2 protein with 100% homology to the human DQB2 sequence. The owl monkey DQB2 allelic sequences and the other chimpanzee DQB2 sequence contain additional polymorphisms, but maintain approximately 95% nucleotide sequence identity with human and the other primate sequences. Identification of the owl monkey DQB2 locus indicates that the ancestral DQ gene duplication event occurred at least 40 million years ago, rather than 10 million years, as previously thought. Remarkably, nucleotide sequences from amplified cDNA indicate that the DQB2 gene, and not the DQB1 gene, may be transcribed in the owl monkey line. Substitutions occur at sites comparable to codons of well-recognized allelic variation in the functional DQB1 genes, implying that variation within the DQB2 locus operates under similar selection constraints to the DQB1 locus, with an extremely high degree of conservation through primate evolution.

Animals↗
PubMed1992

Maintenance of DQB1 polymorphisms in primates.

To understand the evolution of the class II major histocompatibility complex (MHC) DQB1 locus in primates, the second exons of seven DQB1 alleles from five non-human primate species were amplified by polymerase chain reaction. Comparisons of these and other primate sequences show that no between-species diversity is greater than within-species diversity, suggesting maintenance of DQB1 alleles through the history of Old-World primates. There is a preponderance of nonsynonymous nucleotide substitutions at antigen-binding-site codons; this pattern is in marked contrast to what is seen at the closely related, presumably nonfunctional DQB2 gene. The results support the hypothesis that DQB1 polymorphism is maintained by overdominant selection relating to antigen presentation.

Animals↗
PubMed1989

The major histocompatibility complex, MnLA, of pigtailed macaques: definition of fifteen specificities.

The major histocompatibility complex (MHC) of pigtailed macaques (Macaca nemestrina, Mn) is defined and designated as MnLA. Twenty-nine alloantisera were generated by fullsib alloimmunization and tested against a panel of 220 unrelated animals. The reactivities of different alloantisera were analyzed statistically in pairwise comparisons. Using 2 X 2 contingency tables, we calculated chi 2 independence, chi 2 allelism, and correlation coefficient values. Initially, specificities were defined by significant associations of certain sera, but some sera defined specificities individually. In all, 15 specificities were defined, and by family studies and negative correlation coefficients, a two-locus model was evident. Genetic analyses, together with statistical applications, revealed that the behavior of these specificities is consistent with the nature of MHC in other primate species, including man.

Alleles↗
PubMed1988

Conservation of HLA class I private epitopes in macaques.

Fifty mouse monoclonal antibodies (mAb) specific for HLA class I epitopes were compared for their reactivity against two closely related nonhuman primate species, pigtailed macaques (Macaca nemestrina, Mn) and longtailed macaques (M. fascicularis, Mfl), which diverged from the hominoids 23-40 million years ago. An analysis of Nei's genetic identity (I) and distance (D) based on reactivity of all class I-specific mAb showed, as expected, that the macaques are more closely related to each other (I = 0.959) than to man (I = 0.782 for Mn and 0.859 for Mfl). However, there were clear differences in genetic similarity with respect to certain epitopes. Macaques were most different from each other and from man in expression of heterologous epitopes recognized by the mouse that are not polymorphic among humans. In contrast, the most polymorphic epitopes unique to single HLA alleles, so-called private epitopes, were present in all the species, and neither macaque species could be distinguished from humans, suggesting that certain class I private epitopes may be highly conserved in evolution.

Animals↗
PubMed1986

Evolution of HLA class I epitopes defined by murine monoclonal antibodies: distribution in macaques.

Murine anti-HLA monoclonal antibodies (MoAbs) to monomorphic and polymorphic epitopes were compared for their reactivity in humans vs. pigtailed macaques (Macaca nemestrina). Five MoAbs to monomorphic class I epitopes in humans displayed distinct patterns in macaques: two were unreactive, one reacted with 93% of animals tested, another with 17%, and one with only 8% of animals tested. Thus, epitopes that are monomorphic in one species can be highly polymorphic in another. Most of the 23 MoAbs (91%) against polymorphic epitopes in humans also detected polymorphisms in macaques. The epitopes detected by MoAbs could be divided roughly into two groups: epitopes that were expressed at the same frequency in both species, i.e., monomorphic, public, or private epitopes in both species, or epitopes that had quite different expression in the two species, e.g., a "public" epitope in one species expressed as a "private" epitope in the other. The genes encoding some of these polymorphisms were shown to segregate in families and thus some anti-HLA MoAbs are useful typing reagents for macaques. Two MoAbs thought to detect the same specificity in humans were found to react in macaques with different animals. Thus, reactivity patterns of anti-HLA class I MoAbs in primate populations enabled MoAbs to closely associated epitopes to be distinguished.

Animals↗