SEARCH · PubMed Health

Results for “HLA polymorphism”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 217 records · Page 12Linked to original sources

PubMedDate not supplied

DNA polymorphism of HLA class II genes in alopecia areata.

We investigated the DNA restriction polymorphism (RFLP) of the Major Histocompatibility Complex (MHC) class II genes: HLA-DQA, -DQB, -DPA, and -DPB in 20 Danish patients with alopecia areata (AA) and in healthy Danes. The frequency in AA of the DQB1*0301 and DQw7 associated DQB Bgl/II 4.2 kb fragment was increased to 65.0 per cent compared to 23.2 per cent in controls (RR = 6.1; p less than 10(-3)) suggesting that the previously reported associations between AA and both DR4 and DR5 is secondary to an association between AA and DQB1*0301, which codes for the beta-chain of the HLA-DQ molecule of the serologically defined HLA-DQw7 specificity. Individuals who carried both DQA1*0501 and DQB1*0301 seemed to have a further increased risk of developing AA compared to individuals carrying only one of these HLA class II genes. Analysis of the combined presence of DQB1*0301 and DPA1*0103 in AA suggests that an additive risk effect (synergism or interaction) exists between the DQB1*0301 and DPA1*0103 alleles which are situated at different HLA class II loci.

Alopecia Areata↗

PubMed2003

The potential role of HLA-G polymorphism in maternal tolerance to the developing fetus.

The mechanism by which the developing fetus survives the maternal immunity has eluded investigators and remains a central paradox in the field of stem cell research. If the mechanism can be defined, allogenic stem cells may find increased utility after transplantation. While several theories have been advanced, the differential expression of HLA antigens on trophoblasts has been the focus of many studies. Interestingly, an inverse relationship between HLA-G (nonclassical class I molecules) and class I MHC gene expression exists early in pregnancy. HLA-G transcripts are present in quite significant amounts in first-trimester placental tissue, particularly in the extravillous membranes, while the opposite occurs at term. This kind of expression is consistent with the theory that HLA-G might play a role in fetal protection. This could be consequent to either nonimmune (structural) or immune functions at the maternal-fetal interface. Current evidence suggest an immune function wherein HLA-G protects fetal cells from maternal uterine natural killer (NK) cells, which are found in large numbers within cells invading the trophoblasts. This effect has been attributed to maternal NK receptor alterations as well as inhibition of maternal NK cell traffic across the placenta. The recent identification of HLA-G polymorphism brings into play the potential role of these isoforms in fetal protection. Polymorphism may be associated with differential function or may effect linkage disequilibria with other HLA variants, providing fetal protection.

Cell Movement↗

PubMed2003

Polymorphisms of HLA class II predispose children and adolescents with type 1 diabetes mellitus to autoimmune thyroid disease.

To determine the prevalence of autoimmune thyroid disease (AITD) in children and adolescents with type 1 diabetes mellitus (DM), and assess whether the development of AITD is correlated with specific DQ-A and DQ-B loci of the HLA class II antigens, we analyzed thyroid function using anti-thyroid antibodies and HLA-DQ-A and -DQ-B polymorphisms in 69 patients with type 1 DM, in 75 normal healthy controls, and in 21 patients with AITD but without type 1 DM. Eighteen patients (26%) in the diabetic patients had AITD. In the diabetic patients, DQA1*0301 and DQB1*0302 occurred more frequently than in controls [DQA1*0301: OR = 1.939, 95% CI = 1.210-3.109 (P = 0.008, P(c) (corrected P) < 0.05); DQB1*0302: OR = 2.558, 95% CI = 1.354-4.832 (P = 0.005, P(c), > 0.05)]. Compared with controls, non-diabetic subjects with AITD showed higher frequency of DQA1*0301 (P(c), < 0.05) and DQB1*0601 (P(c) > 0.05), but these alleles were not contributing factors in the development of AITD in diabetic patients. In diabetic patients, DQB1*0201, known as susceptible allele of type 1 DM was not a contributing factor in the development of AITD in diabetic patients. Unlike DQB1*0201, DQB1*0401 was more frequently found in diabetic patients with AITD than in controls [OR = 4.053, 95% CI = 1.607-10.221 (P = 0.0017, P(c) < 0.05)] or than in non-diabetic AITD patients [OR = 15.769, 95% CI = 1.905-130.530(P = 0.002, P(c) < 0.05)]. In non-diabetic subjects, DQB1*0401 did not provide susceptibility for AITD. Our results suggest that HLA DQB1*0401 is a predisposing genetic marker for the development of AITD in patients with type 1 DM in Korea.

Adolescent↗

PubMed1997

HLA-G polymorphism in Finnish couples with recurrent spontaneous miscarriage.

HLA-G is a class I major histocompatibility complex gene that is expressed in cytotrophoblasts at the materno-fetal interface. It has been suggested that HLA-G could play a key role in materno-fetal immunological interactions during pregnancy. To investigate whether there is an association between HLA-G locus and recurrent spontaneous miscarriage, HLA-G alleles were determined by a PCR-RFLP method in 38 couples with recurrent spontaneous miscarriage and in 26 random control couples. In this series parental HLA-G sharing, extended HLA-G/A haplotypes and the frequencies of the HLA-G alleles were similar in the two groups. Thus, our data suggest that there is no detectable relation between susceptibility to recurrent spontaneous miscarriage and HLA-G locus.

Abortion, Habitual↗

PubMed1998

MICA, a new polymorphic HLA-related antigen, is expressed mainly by keratinocytes, endothelial cells, and monocytes.

MICA is a new polymorphic gene in the HLA region expressed in epithelial cell lines and gastrointestinal epithelium. Little is yet known about the MICA protein, and the pattern of its expression by freshly isolated cells has not been established. In the present experiments, we used antibodies raised in rabbits against alpha1 and alpha2 domain-peptides to study the expression of MICA. By western blot and immunoprecipitation, we detected a band of 62 000 Mr in various cell lines (THP-1, U937, HeLa, A431, Raji, MOLT-4, and HUV-EC-C) and in freshly isolated keratinocytes, endothelial cells, and monocytes but not in CD4+ and CD8+ T cells, and CD19+ cells (B lymphocytes). It was not possible to up-regulate the expression of MICA in different cells by stimulation with gamma-interferon, but the expression of MICA was induced in phytohemagglutinin-stimulated T cells. We confirmed that MICA is expressed at the cell surface by flow cytometry. Results of immunoprecipitation studies of beta2-microglobulin (beta2m)- or MICA-depleted, metabolically labeled HeLa cells indicated that MICA was not associated with beta2m. Although the function of MICA is still unknown, its restricted pattern of tissue expression, the fact that it is expressed on the cell surface, and its polymorphic nature suggest that this new molecule, encoded close to HLA class I, may play a role in the interaction between epithelial cells and cells of the immune system.

Amino Acid Sequence↗

PubMed2004

Association of HLA-DM polymorphism with the production of antiphospholipid antibodies.

OBJECTIVE: To investigate whether variation in the HLA-DM gene is important in producing a group of pathogenic autoantibodies-antiphospholipid antibodies (aPL)-on the basis that HLA class II restricted antigen presentation is involved in the production of aPL. METHODS: HLA-DMA and DMB polymorphisms were genotyped by polymerase chain reaction combined with restriction enzyme digestion in 51 white patients with primary antiphospholipid syndrome (APS), 82 with systemic lupus erythematosus (SLE) (42 with APS and 40 without APS), and 109 healthy white controls. The association with the aPL profile was examined. RESULTS: The distribution of DMA alleles in APS patients and in patients with APS associated with SLE was significantly different from that in controls by 4x2 chi(2) test with 3 degrees of freedom (p = 0.035 and 0.011, respectively), but it was not different between SLE patients without APS and controls. The allelic distribution of DMA was also different between patients with IgG class anticardiolipin antibody or those with lupus anticoagulant (LA) and controls (p = 0.012 and 0.007, respectively) and between patients with and without LA among SLE patients (p = 0.035). All these differences included the increase in DMA*0102 in the former groups. CONCLUSIONS: The results suggest that HLA-DMA*0102 or its linked gene(s) form one of the genetic risks for the production of aPL.

Adult↗

PubMedDate not supplied

HLA-DQ polymorphisms modify the risk of thyroid autoimmunity in children with type 1 diabetes mellitus.

OBJECTIVE: Type 1 diabetes mellitus (DM1) is frequently accompanied by thyroid autoimmunity (TAI). The aims of the present study were to estimate the prevalence of TAI and to determine the contribution of HLA-DQA1 and -DQB1 polymorphisms to TAI susceptibility among children with DM1. PATIENTS AND METLHODS: Screening for TAI was performed in 285 children with DM1 by measuring autoantibodies against thyroid peroxidase (anti-TPO) and thyroglobulin (anti-Tg). HLA-DQA1 and -DQB1 were genotyped using PCR-SSP. RESULTS: Repeated positivity of anti-TPO and/or anti-Tg was found in 45/285 children with DM1 (15.8%). The prevalence was significantly higher in girls than in boys (26.7% vs 6.7%; p<10(-5)). The HLA-DQB1*0302 allele conferred susceptibility to TAI in children with DM1 (OR 2.7, 95% CI 1.1-6.4), while the DQB1*05 alleles acted protectively (OR 0.2, CI 95% 0.08-0.7). CONCLUSIONS: HLA-DQ polymorphisms significantly modify the risk of TAI in children with DM1.

Adolescent↗

PubMedDate not supplied

Sequence polymorphism of HLA DR beta 1 alleles relating to T-cell-recognized determinants.

HLA class II molecules are a highly polymorphic family of dimeric cell-surface proteins primarily involved in regulating T-cell responses to extrinsic antigens. To define regions of class II molecules involved in T-cell recognition, we have now compared sequences of three HLA DR beta cDNA clones obtained from cells that all express the same serologically defined determinants but differ in terms of T-cell-recognized specificities. The comparisons indicate that very few (one to four) nucleotides differ between what are almost certainly alleles of the DR beta 1 locus. All differences were in the first domain of the molecule and all localized to a region from amino acids 71-86. Because all differences were found only in this region of the molecule, and because DR alpha-chains seem to be relatively non-polymorphic, these positions in the DR beta-chain must have a major role in influencing T-cell recognition of the DR molecule.

Alleles↗

PubMed1996

HLA-DPB1 polymorphism in seven South American Indian tribes in Colombia.

HLA-DPB1 allele frequencies were investigated in seven geographically and linguistically distinct Amerindian tribes of Colombia. Allele *1301 was found only in the Embera tribe living along the Pacific coast, while allele *0101 was found only in two individuals of the Wayuu tribe inhabiting the Guajira desert. Significant geographical variation was observed in the other two alleles (*1401 and *0402), which were found in all seven tribal groups. The possible reasons for this restricted polymorphism and the genetic diversity found in the investigation are discussed.

Alleles↗

PubMed1997

HLA-DR polymorphism modulates the cytokine profile of Mycobacterium leprae HSP-reactive CD4+ T cells.

In the present study, in vitro attempts have been made to define the cytokine profile of CD4+ T cells from polar leprosy patients and healthy individuals against Mycobacterium leprae-derived heat shock proteins (HSPs), HSP65 and HSP18, and their trypsin-digested fragments, relating to HLA-DR polymorphism. While all tryptic fragments of optimal digestion and undigested HSPs could stimulate CD4+ T cells from tuberculoid (TT) leprosy patients and healthy contacts (stimulation index, SI > 2.0), only two fragments, TDB65-2 (18 kDa) and TDB18-3 (3 kDa) triggered CD4+ T cells of anergic lepromatous (LL) leprosy patients. Both of these HSPs and their tryptic fragments showed diverse HLA-DR restriction, with DR15 providing the strongest restriction. Cytokine analysis demonstrated that HSP65 and HSP18 induced Th1-like activity in the context of all the restricting HLA-DR alleles, except DR1 and DR7 which induced a Th2 type of response against HSP65 and HSP18, respectively. These Th2 inducer epitopes on HSP65 (DR1 restricted) and HSP18 (DR7 restricted) were absent from TDB65-2 and TDB18-3 which exclusively triggered Th1 cells in both TT and LL forms of leprosy in the context of multiple DR alleles, DR15 being the major antigen-presenting allele. These studies suggest that the major histocompatibility complex phenotype of the antigen-presenting cell can modulate Th1-like versus Th2-like activity against M. leprae pathogens in leprosy and healthy individuals.

Adjuvants, Immunologic↗

PubMed1997

HLA-DQB1 polymorphism determines incidence, onset, and severity of collagen-induced arthritis in transgenic mice. Implications in human rheumatoid arthritis.

Certain HLA-DR alleles have been associated with predisposition to human rheumatoid arthritis (RA). There is also evidence that certain HLA-DQ alleles may also be important in determining susceptibility to RA. We have previously demonstrated that mice transgenic for HLA-DQ8, a DQ allele associated with susceptibility to RA, develop severe arthritis after type II collagen immunization. To investigate the influence of polymorphic difference at the DQ loci on susceptibility to arthritis, we generated mice transgenic for HLA-DQ6, an allele associated with a nonsusceptible haplotype. The DQ6 mice were found to be resistant to collagen-induced arthritis. We also assessed the combined effect of an RA-susceptible and an RA nonassociated DQ allele by producing double-transgenic mice expressing DQ6 and DQ8 molecules, representing the more prevalent condition found in humans where heterozygosity at the DQ allele is common. The double-transgenic mice developed moderate CIA when immunized with CII when compared with the severe arthritis observed in DQ8 transgenic mice, much like RA patients bearing both susceptible and nonsusceptible HLA haplotypes. These studies support a role for HLA-DQ polymorphism in human RA.

Age Factors↗

PubMed1992

HLA-DP polymorphism in northern Italian celiac patients.

The contribution of HLA-DP genes to celiac disease susceptibility has been investigated in 95 Italian patients, 41 with childhood and 54 with adult disease onset. Polymerase chain reaction amplification, sequence-specific oligonucleotide probe hybridization and restriction fragment length polymorphism analyses have been carried out. All celiac patients and 56 out of 128 random healthy controls were DQw2-positive. The frequency of the DPB1*0101 allele was significantly increased (pc = 0.002, relative risk 5.21) in patients with celiac disease (23.2%) compared to the whole panel of controls (5.5%), but not to the 56 controls bearing DQw2 (10.7%). No significant difference in the frequency of DPB1*0101 was found between celiac patients with pediatric (24.4%) or adult (22.2%) onset. The DPB1*0101 allele was associated with both the DR3-DQw2 and DR7-DQw2 haplotypes. Moreover, our study has not confirmed the association with DPB1*0402 and DPB1*0301 previously reported in celiac children from southern Italy. The linkage of the DPB1*0101 allele with the DQ locus and the observation that the DP but not the DQ association appears to be ethnically dependent strongly support a secondary role of DP molecules in celiac disease susceptibility.

Adult↗

PubMed1998

An HLA-B27 polymorphism (B*2710) that is critical for T-cell recognition has limited effects on peptide specificity.

The B*2710 subtype differs from the HLA-B27 prototype (B*2705) only by having Glu instead of Val at position 152, in the alpha2 helix of the peptide-binding site. In spite of its structural similarity most alloreactive CTL raised against B*2705 fail to cross-react with B*2710. Indeed, of the residues that are polymorphic among HLA-B27 subtypes, the Val>Glu152 change has the greatest influence on HLA-B27 T-cell antigenicity. The molecular basis for this antigenic disparity was analyzed in this study. Sequence analysis indicated that B*2710-bound peptides have very similar motifs to B*2705-bound ones both at the main and auxiliary anchor positions. In addition, most of the individual ligands sequenced from B*2710 were previously found in B*2705. Together these results indicate that both subtypes have largely overlapping peptide repertoires. Molecular dynamics simulations of a common ligand in complex with either B*2710 or B*2705 failed to detect significant conformational changes in the peptidic main chain or in solvent accessibility of the side chains. In addition, modeling of the Val>Glu152 change into the MHC-peptide-TCR structure suggested a direct role of residue 152 in interaction with the TCR. Thus, the large differences in T-cell recognition between B*2710 and B*2705 are not explained by an effect of the Glu152 change on peptide specificity or conformation, but by different direct interactions with the TCR.

Binding Sites↗

PubMedDate not supplied

Immunogenetics of rheumatoid arthritis and primary Sjögren's syndrome: DNA polymorphism of HLA class II genes.

We investigated the DNA restriction fragment length polymorphism (RFLP) of the Major Histocompatability Complex (MHC) class II genes: HLA-DRB, -DQA, -DQB, DPA, and -DFB in 24 patients with rheumatoid arthritis (RA), in 19 patients with primary Sjögren's syndrome (primary SS), and healthy Danes. The frequencies of DNA fragments associated with the following HLA class II genes were increased in RA when compared to normal controls: DRB1*04 (DR4) (relative risk, RR = 7.4, P less than 10(-3), DRB4*0101 (DRw53) (RR = 9.6, P less than 10(-3), DQA1*0301 (RR = 9.6, P less than 10(-3), DQB1*0301 (DQw7) (RR = 2.8, P less than 0.05, 'corrected' P greater than 0.05), and DQB1*0302 (DQw8) (RR = 4.5, P less than 10(-2). Negative associations were found between RA and DRB1*1501 (DR2/DRw15) (RR = 0.2, P less than 10(-2) and DQB1*0602 (DQw6) (RR = 0.2, P less than 10(-2), 'corrected' P greater than 0.05). The frequencies in RA of other HLA class II associated DNA fragments including DPA and DPB and the antigens DPw1-w6 defined by primed lymphocyte stimulation, did not differ significantly from those in controls. In primary SS, the frequency of HLA-B8 was significantly increased (RR = 9.0, P less than 10(-3). Positive associations were found between primary SS and DNA fragments associated with DRB1*03/13 (RR = 6.8, P less than 10(-3), DRB3*0101 (DRw52) (RR = 5.7, P less than 10(-2), DQA1*0501 (RR = 6.8, P less than 10(-3), DQB1*0201 (DQw2) (RR = 11.6, P less than 10(-5), and DQB1*0602 (DQw6) (RR = 2.7, P less than 0.05, 'corrected' P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Arthritis, Rheumatoid↗

PubMed1982

[Polymorphism of HLA genes: I. Demonstration of a close correlation between DNA fragments determined by BglI restriction enzyme and HLA class I antigens].

Description of DNA fragments associated to HLA class I gene is possible by using restriction enzymes which determine these fragments and specific DNA probes which permit their detection. In one family, with a child presenting a recombination between HLA-A and C, six fragments determined by the enzyme BglI were found to be polymorphic. The informative fragments segregate with HLA, either with a whole haplotype or with one of the two recombinant segments of the HLA complex. In a small sample of population they correlate with one (A11) or with a group of known cross-reactive antigens serologically defined (A3 and A11; A25 and A26. Another fragment is associated with unknown cross-reactive antigens (A2 and A29).

DNA↗

PubMed1984

Enzyme-linked immunosorbent assay for determination of HLA: gene dose effect.

In a previous publication we demonstrated that polymorphic HLA antigens could be detected on fresh and dried peripheral blood lymphocytes using the enzyme-linked immunosorbent assay (ELISA) with HLA alloantisera (Bishara et al. 1983). In the present study we investigated whether the ELISA technique can be used in determination of gene-dose effect for antigens of the HLA-A and B loci. Lymphocytes from HLA-A1 and HLA-B14 homozygous individuals are shown to bind significantly more anti-HLA alloantibodies than their heterozygous siblings for the same HLA antigens. These results indicate that ELISA is a sensitive and reliable technique for the qualitative and quantitative assay of polymorphic HLA determinants.

Adult↗

PubMed1985

[Detection of polymorphism of HLA class II genes using synthetic oligonucleotides].

The recent sequence determination of exons of various HLA class II genes has allowed us to study the polymorphism of coding sequences of these genes on a sample of HLA-DR typed unrelated individuals. From this sequence determination have emerged polymorphic hypervariable areas. A 24-mer oligonucleotide has been synthetized, which corresponds to the first hypervariable region of the beta 1 domain of a DR-beta molecule. This oligonucleotide hybridized only with the DNA from DR3 or DR5 individuals tested, even under stringent conditions of washing. However, the existence of strong linkage disequilibrium among the 3 or 4 DR genes of the D region does not allow us to conclude that this sequence is epitope-specific.

Genes, MHC Class II↗

PubMed2002

HLA-DRB1 and HLA-DQB1 polymorphisms in Pacific Islands populations.

Allele frequency distributions of the HLA-DRB1 and HLA-DQB1 genes were investigated in four Pacific Islands populations from the Cook Islands, Samoa, Tokelau and Tonga. Limited diversity was observed for both the HLA-DRB1 and HLA-DQB1 loci. Five HLA-DRB1 alleles were observed to be the most frequent amongst all the studied Pacific Islands populations. They were: HLA-DRB1*0403, HLA-DRB1*08032, HLA-DRB1*09012, HLA-DRB1*11011 and HLA-DRB1*1201. Cook Islanders had the largest number of low frequency DRB1 alleles followed by Samoans, Tokelauans and Tongans, most of which may be attributed to reported non-Polynesian admixture. The most frequently observed DQB1 alleles in the four studied Pacific Islands populations were those of the DQ3 subgroup of alleles HLA-DQB1*03011, HLA-DQB1*0302 and HLA-DQB1*03032 as well as HLA-DQB1*05031 and HLA-DQB1*06011. Cook Islanders had the highest number of rare HLA-DQB1 alleles, the distibution being similar to that of the HLA-DRB1 allele. While, in general, the values of homozygosity for DRB1 and DQB1 were observed to be lower then expected under neutrality, a statistical significance was observed in Tongans, Samoans and Tokelauans for the DQB1 locus and in Tongans for the DRB1 locus. Differences were observed between allele frequency distributions for Tokelauans compared to the other three populations. This was also demonstrated by principal component analysis of DRB1 and DQB1 allele frequencies, which separated the Tokelauan population from Cook Islanders, Tongans and Samoans. Tongans and Samoans were separate from the other Polynesian populations in the phylogenetic trees. Observed allele and haplotype frequencies were found to be in agreement with previously published HLA-DRB and HLA-DQB Polynesian data.

Asian People↗