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PubMed1991

HLA typing in polymorphous light eruption.

Human leukocyte antigen typing of 41 white patients with polymorphous light eruption (limited concept) showed no significant differences when compared with the typing of 51 white control subjects. We previously found that actinic prurigo, an idiopathic photodermatosis particularly associated with Amerindians, has a positive association with antigens A24 and Cw4 and a negative association with A3. We suggest, on the basis of both laboratory and clinical findings, that polymorphous light eruption (limited concept) and actinic prurigo are two different and distinct diseases.

Adolescent↗

PubMedDate not supplied

[HLA molecules, immunity and gestation].

During pregnancy, the fetus develops particularly efficient molecular regulatory mechanisms to prevent possible maternal anti-paternal alloimmune response and avoid viral spreading from maternal tissue. Among the different mechanisms, there has been noted a selective expression of HLA molecules on trophoblast cells: the absence of HLA class II and of polymorphic HLA-A and HLA-B expression but presence of both non polymorphic HLA-G and HLA-E class Ib as well as of HLA-C class Ia. The functional consequences of such a particular pattern of HLA expression in gestation are examined here.

Female↗

PubMed1987

HLA and C4 polymorphism in diabetic microangiopathy.

We have reported an increased frequency of the rare B3 allotype of the fourth component of complement (C4B3) in insulin-dependent diabetics, especially in those with microangiopathy. This study has now been expanded--20 of 106 subjects with microangiopathy and 9 of 116 without possessed the C4B3 allotype (p less than 0.02). C4B3 is said to be in linkage disequilibrium with HLA-DR4. HLA typing was performed on 94 of these patients, 52 with and 42 without microangiopathy. There was no significant difference in the frequency of DR4 (62 vs 50%), DR3 (65 vs 52%), B8 (40 vs 40%) or B15 (32 vs 19%) respectively between these 2 groups. These results confirm an HLA-linked predisposition to microangiopathy, but do not determine whether the primary association is with C4B3, DR4 or another gene with which they are in linkage disequilibrium.

Complement C4↗

PubMed2003

HLA-DRB1, DQB1 and DPB1 polymorphism in the Naxi ethnic group of South-western China.

Polymorphism of HLA-DRB1, DQB1 and DPB1 was revealed with a sequencing-based typing (SBT) method in unrelated healthy volunteers from the Naxi ethnic group. Among the 43 DRB1 alleles detected, the most common allele was DRB1*12021 with a frequency of 17%, followed by DRB1*08032, DRB1*09012 and DRB1*1404 with frequencies of 8.5%, 7.4% and 7.4%, respectively. Among 23 DQB1 alleles detected, the most frequent DQB1 allele was DQB1*03011/0309 (21.9%), followed by DQB1*0502 (16.4%) and DQB1*05031 (9.6%). For the DPB1 locus, the most common alleles were DPB1*0501 (25.5%), DPB1*0402 (14.6%) and DPB1*02012 (12.0%). The most common DRB1-DQB1-DPB1 haplotype was DRB1*1404-DQB1*05031-DPB1*0402 with a frequency of 5.26%, followed by the DRB1*08032-DQB1*06011-DPB1*1301 (3.51%). The distribution characteristics of the HLA class II alleles revealed that the Naxi ethnic group belonged to the Southern group of Chinese.

Alleles↗

PubMed2000

New revelations in susceptibility to autoimmune thyroiditis by the use of H2 and HLA class II transgenic models.

H2 and HLA transgenes were utilized to clarify the role of class II genes in susceptibility to experimental autoimmune thyroiditis (EAT), a model for Hashimoto's thyroiditis (HT). Susceptibility was transferred by H2 class II transgenes to a resistant haplotype and by HLA-DRA/DRB1*0301 (DR3) transgene into class II-negative Ab0 mice. Mice with a HLA-DRB1*1502 (DR2) transgene remain resistant to mouse thyroglobulin (mTg)-induced EAT, illustrating the role of HLA-DRB1 polymorphism. A role for HLA-DQ polymorphism was shown with hTg-induced EAT in HLA-DQ*0301/DQB1*0302 (DQ8), but not HLA-DQ*0103/DQB1*0601 (DQ6), transgenic mice. Yet, both DQ8+ and DQ6+ mice were unresponsive to mTg. Single transgenes obviate the problems from DR/DQ linkage disequilibrium and may distinguish the degree of susceptibility and the response to shared or specific epitopes. The introduction of conserved Eak transgene into Ab0 mice reveals a new role for H2E molecules in EAT. Without H2A molecules, EalphaEbetab molecules and T cells respond to hTg or pTg with severe thyroiditis, but not to mTg, thus distinguishing self from nonself. However, IAb genes in resistant mice ameliorate Eak transgene-mediated thyroiditis, similar to the effect of Eak transgene on IAs-mediated EAT. Studies in HLA DQ/DR double transgenic mice simulating human haplotypes could reveal HLA class II gene interactions in HT.

Animals↗

PubMed2003

HLA class II polymorphisms and susceptibility to recurrent respiratory papillomatosis.

Recurrent respiratory papillomatosis (RRP) is characterised by multiple laryngeal papillomas. Left untreated, the lesions enlarge, spread, and endanger the airway. Medical treatments are unsatisfactory, and repeated surgery remains the mainstay of therapy. RRP is caused by human papillomavirus (HPV) infection. However, since oral HPV infection is common and RRP is rare, other host and/or viral factors may contribute to pathogenesis. In an attempt to identify such factors, we have investigated 60 patients. The patients were HLA class I, II, and tumor necrosis factor TNF typed by sequence-specific primer PCR, and the results compared to those for 554 healthy controls by using Fisher's exact test. Peripheral blood mononuclear cell proliferative responses of 25 controls and 10 patients to HPV-11 L1 virus-like particles (VLP) were compared. Short-term VLP-specific T-cell lines were established, and recognition of L1 was analyzed. Finally, the L1 open reading frames of HPV isolates from four patients were sequenced. Susceptibility to RRP was associated with HLA DRB1*0301 (33 of 60 patients versus 136 of 554 controls, P < 0.0001). The three most severely affected patients were homozygous for this allele. A range of T-cell proliferative responses to HPV-11 VLP were observed in DRB1*0301-positive healthy donors which were comparable to those in DRB1*0301-negative controls. Individuals with juvenile-onset RRP also mounted a range of VLP responses, and their magnitude was negatively correlated with the clinical staging score (P = 0.012 by the Spearman rank correlation). DRB1*0301-positive patients who responded to L1 recognized the same epitope as did matched controls and produced similar cytokines. Sequencing of clinical isolates excluded the possibility that nonresponsiveness was the result of mutation(s) in L1.

Adolescent↗

PubMed1989

Specificity of human T lymphocytes expressing a gamma/delta T cell antigen receptor. Recognition of a polymorphic determinant of HLA class I molecules by a gamma/delta clone.

Alloreactive clones expressing T cell receptor (TcR) gamma/delta were derived by limiting dilution from CD3+ CD4- CD8- WT31- populations stimulated in allogeneic mixed lymphocyte culture. These clones specifically lysed phytohemagglutinin-induced blast cells bearing the stimulating alloantigens, whereas they had no effect on autologous or allogeneic unrelated target cells. Analysis of the reactivity with monoclonal antibodies (mAb) specific for two different subsets of TcR gamma/delta (BB3 and delta-TCS-1) showed that five out of nine clones were BB3+, whereas the remaining reacted with delta-TCS-1. Therefore, we can conclude that both subsets of TcR gamma/delta+ cells are able to specifically recognize and lyse allogeneic cells. mAb directed against the CD3-TcR gamma/delta molecular complex strongly inhibited the specific cytolytic activity of TcR gamma/delta+ clones, whereas they had no effect on the lysis of the natural killer-sensitive K-562 target cells mediated by the same clones. An alloreactive delta-TCS-1+ clone (LM12) was further characterized for its specificity. LM12 clone had been derived after stimulation in mixed lymphocyte culture against donor M.M. (HLA typing: Aw68, 24; B35, w55; DR1, 7). The analysis of a large panel of phytohemagglutinin-induced target cells revealed that only the HLA-A24+ target cells were lysed. The direct evidence that the A24 molecule represented the restriction element was provided by experiments using A24-transfected murine P815 target cells. Thus, clone LM12 efficiently lysed A24-transfected P815 cells, but not the same cells untransfected or transfected with the Cw3 gene. Therefore, it appears that polymorphic determinants of class I major histocompatibility complex molecules can be the target of TcR gamma/delta+ alloreactive cell recognition.

Antibodies, Monoclonal↗

PubMed1988

Restriction fragment length polymorphisms and an HLA-DRw52-associated split.

The restriction fragment length polymorphism technique, employing seven restriction endonucleases, and a DR-specific repeated element probe were used to study a large panel of homozygous typing cells in order to delineate haplotypic differences within the HLA-DRw52 supertype. Most of the restriction endonucleases revealed the presence of two allelic restriction fragment length polymorphisms correlating with and splitting the HLA-DRw52 supertypic specificity. One designated A, correlated with the HLA-DRw52 typing in HLA-DR5, HLA-DR3, (non-A1, B8), and some HLA-DRw6 haplotypes. The other, designated a, correlated with the HLA-DRw52 typing in HLA-DR5, HLA-DRw8, HLA-DR3 (A1, B8), and the remaining HLA-DRw6 haplotypes. The general applicability of these findings was validated in 47 HLA-typed laboratory controls.

Alleles↗

PubMed1992

HLA-DR,DQ nucleotide sequence polymorphisms in five Melanesian populations.

HLA-DRB1 nucleotide sequence polymorphisms have been examined in 304 Melanesians from the Papua New Guinean coast (Madang), islands (Rabaul) and highlands (Goroka), and from New Caledonia and Fiji. A total of 20 HLA-DRB1 alleles were detected by oligonucleotide hybridizations of exon 2 HLA-DRB1 polymerase chain reaction products, in a typing protocol designed to detect all 42 officially-designated HLA-DRB1 alleles. DRB1*1502 and 1101 alleles were the most common alleles in coastal and island Melanesians, while DRB1*1501, 1502 and 1408 predominated in Papua New Guinean highlanders. Undefined mixed lymphocyte reaction determinants in earlier studies of Melanesians could be accounted for in the present study as DRB1*0410, 1407 and 1408 in Papua New Guinean highlanders and as DRB1*1104 and 1602 in coastal people. Nucleotide sequence polymorphisms at HLA-DQA1, -DQB1, -DRB3 and -DRB5 were also determined for estimating HLA-DR,DQ allelic disequilibrium relationships; unusual haplotypes in Melanesians included DBR1*1502, DRB5*0101 and DRB1*0410, DQB1*0402. Previous claims of limited heterogeneity in the HLA-DR allele repertoire in Melanesians are now seen to reflect limitations of early typing reagents rather than any dramatic restriction in HLA-DR allelic diversity.

Alleles↗

PubMed1996

HLA-DQ gene polymorphism in primary IgA nephropathy in three European populations.

MHC Class II genes may contribute to susceptibility to IgA nephropathy (IgAN). We have previously identified a restriction fragment length polymorphism (RFLP) of the DQB1 region that associated with IgAN in British Caucasoids. However, another group, while demonstrating a DQB1 association, was unable to confirm our finding. MHC molecules are heterodimers consisting of an alpha and beta chain, and thus polymorphism of the DQA1 alpha chain may also be important to disease pathogenesis in IgAN. Therefore, we have determined DQA1 alleles and re-examined DQB1 alleles in British Caucasoids with IgAN using an approach that can differentiate between the common DQ alleles; we have also extended our studies to Caucasoid populations from Northern and Southern Europe, thereby addressing the possibility of variation in genetic susceptibility between populations. DNA was prepared from IgAN patients (British, N = 105; Italian, N = 71; Finnish, N = 48) and healthy controls (British, N = 111; Italian, N = 63; Finnish, N = 41). DQA1 alleles were identified by TaqI RFLP and Southern blotting; alleles that could not be fully resolved by Taq Southern blotting were identified by PCR-RFLP. DQB1 alleles were identified by polymerase chain reaction (PCR) based technique (PCR-RFLP). No consistent association of DQ alleles were found between the populations studied. In British patients a decreased frequency of DQB1*0201 was observed (P = 0.008), in Finnish patients a decreased frequency of DQB1*0602 was observed (P = 0.01), and in Italian patients no association between DQ markers and IgAn was found. These data demonstrate population variation in disease association, but no strong or consistent association in the DQ region.

Alleles↗

PubMed1989

Lack of informative HLA restriction fragment length polymorphisms in autoimmune chronic active hepatitis.

Autoimmune chronic active hepatitis (CAH) is strongly associated with HLA-B8, DR3. Accordingly, DNA was isolated from 10 HLA-B8, DR3 control subjects and 11 patients with autoimmune CAH and analyzed for informative restriction fragment length polymorphisms using HLA-DQ beta and DR beta probes, and six enzymes, Hinc II, Bgl II, Bam HI, Rsa I, Taq I and Msp I. None of the polymorphic fragments demonstrable was discriminatory for autoimmune CAH. A genetic polymorphism in the HLA-B8, DR3 region predisposing to autoimmune CAH may not have been detecting owing to an insufficient number of probes or enzymes used, or alternatively HLA-DR3 is predisposing by an effect on immune regulation or suppression.

Adult↗

PubMed1996

New highly polymorphic microsatellite marker in linkage disequilibrium with HLA-B.

The difficulty of molecular typing of the HLA class I genes and the relevance of the genes of this region to disease susceptibility and transplantation have provided an impetus to develop useful typing markers. We have characterized by polymerase chain reaction analysis a new highly informative CA repeat localized approximately 25-kb centromeric to the gene HLA-B and 10-kb telomeric to the gene MICA. Twelve alleles defined by length were found in a sample of French Basques, with the PIC being 0.82. A detailed haplotype analysis was performed to investigate the association between this microsatellite and two others markers of the region (HLA-B gene and TNF region microsatellite). The 10 haplotypes with the highest estimated frequencies show evidence of a gametic association or linkage disequilibrium. A very strong association between the expressed HLA-B polymorphism and microsatellite alleles was also revealed in this sample and confirmed in the workshop cells lines of the Fourth Asia-Oceania Histocompatibility Workshop. This marker can be used in the fine mapping of this region and the association with some alleles of HLA-B may allow the replacement of HLA-B typing at least in a preliminary study. Moreover, these studies support the hypothesis of a high mutability for large alleles in microsatellite loci.

Alleles↗

PubMedDate not supplied

Extended haplotype analysis reveals an association of TNF polymorphisms with susceptibility to systemic lupus erythematosus beyond HLA-DR3.

OBJECTIVE: To study the relative contribution of tumour necrosis factor (TNF) and HLA-DRB1 polymorphisms to the genetic susceptibility to systemic lupus erythematosus (SLE) via an extended haplotype analysis. METHODS: We performed an association study in 205 unrelated German Caucasian patients with SLE fulfilling the 1997 revised American College of Rheumatology (ACR) criteria. Healthy age-, ethnically- and sex-matched individuals (n = 157) served as controls. HLA-DRB1 typing was performed by a sequence-specific oligonucleotide hybridisation assay. Two TNF single nucleotide polymorphisms (SNPs) and two multiallelic microsatellites were analysed by mutagenically separated polymerase chain reaction (PCR) or fragment length analysis, respectively. Extended haplotypes were reconstructed with the PHASE software. RESULTS: Alleles for all polymorphic loci studied and the most frequent haplotypes showed a significantly different distribution between SLE patients and controls. The alleles HLA-DR2, DR3, TNFd1, TNF2, TNFB*1, and TNFa2, designated as risk alleles, and the extended haplotypes DR3-TNFd1-TNF2-TNFB*1-TNFa2 and DR2-TNFd3-TNF1-TNFB*2-TNFa11 prevailed in SLE patients. TNF risk alleles were strongly positively linked with HLA-DR3 and negatively linked with HLA-DR2. Thus, in HLA-DR3 haplotypes individual effects of TNF polymorphisms could not be resolved. By contrast, HLA-DR2 showed an association with SLE independently of TNF risk alleles, while the risk increased further when they were present. In haplotypes lacking HLA-DR2 and DR3, the alleles TNFdl and TNF2 contributed independently to SLE susceptibility. CONCLUSION: Extended haplotype analysis revealed HLA-DR3 independent associations of TNF polymorphisms with susceptibility to SLE. Haplotypes that have been shown to be associated with different TNF-alpha production capacity may prevail in different disease subgroups.

Adolescent↗

PubMed2005

[Determination of HLA-A, -B allele polymorphism in the Luoba nationality living in Tibet Autonomous Region in China].

OBJECTIVE: To investigate the HLA-A, -B allele polymorphism in the Luoba ethnic population. METHODS: HLA-A, -B DNA types in 92 healthy individuals of Luoba nationality in the Linzhi area, Tibet Autonomous Region, were investigated by polymerase chain reaction-sequence specific oligo-nucleotide (PCR-SSO). RESULTS: Ten alleles at HLA-A locus, and 19 alleles at HLA-B locus in Luoba ethnic group were detected. Of the 10 HLA-A alleles detected, the three most common alleles were HLA-A*11(allele frequency: 36.40%), -A*02 (25.50%), -A*24 (23.90%), and they covered 85.80% of the total HLA-A alleles detected from the Luoba ethnic group. Of the 19 HLA-B alleles detected, the three most common alleles were HLA-B*40 (27.20%), -B*15 (11.40%) and -B*38(10.90%), and they covered 49.50% of the total -B alleles detected in the Luoba ethnic group. CONCLUSION: The distribution of HLA-A, -B allele polymorphism in the Luoba nationality is distinctive, but some of the gene distribution in the Luoba group is nearer to that in the Tibetan group. These are consistent with the results of ethnological, historical and sociological researches.

Alleles↗

PubMed1986

HLA-DQ beta-chain polymorphism linked to myasthenia gravis.

The HLA-DR3 haplotype is associated with increased risk of myasthenia gravis (MG) and a number of other autoimmune diseases, including insulin-dependent diabetes mellitus (IDDM), coeliac disease, and premature ovarian failure (POF). With a cDNA probe for a DQ beta gene, a 15 kb Hinc II restriction fragment has been demonstrated in genomic DNA from 7 of 16 HLA-DR3 patients with MG, 1 of 19 healthy DR3 controls, and none of 24 DR3 patients with IDDM, coeliac disease, or POF. The HLA-DQ polymorphism may be closely linked to a genetic locus regulating immune responsiveness to acetylcholine receptor and susceptibility to MG.

Celiac Disease↗

PubMed2004

[Analysis of polymorphism of the HLA-DRB1 gene in populations from the Volga-Ural region].

Polymorphism at the HLA-DRB1 locus in six Turkic (Bashkirs, Tatars, and Chuvashes) and Finno-Ugric (Udmurts, Maris, and Komis) populations of the Volga--Ural region was studied by PCR. A total of 12 DRB1 specificities displaying population-specific frequency distribution patterns were described. The most frequently observed specificities in Bashkirs and Udmurts were DRB1*07 (25 and 34%, respectively) and *15 (by 15%). In Tatars the prevalence of *04 (18%), *01 (17%), *07 (16%) and *15 (13%) specificities was observed, while in Chuvashes these were *04 (28%), *11 (18%), *01 (16%), and *07 (16%). High frequencies of *11 (21%), *04 (17%), *01 (13%), and *04 (11%) specificities were characteristic of Komis, whereas Maris were distinguished by high frequencies of *01 (23%), *11 (14%), *07 (13%), and *04 (11%). In general, the pattern of DRB1 allelic polymorphism in populations of the Volga-Ural region, occupying the intermediate position between the Caucasoid- and Mongoloid-specific allelic frequency distribution patterns, was consistent with their anthropological type rather than with their linguistic affiliation.

Ethnicity↗

PubMed1995

HLA complement gene polymorphisms in multiple sclerosis. A study on 80 Italian patients.

We studied C4A, C4B, and Bf complement gene polymorphisms in 80 Italian patients with multiple sclerosis (MS). We observed a significantly higher frequency of C4AQ0 allele in patients with the relapsing-remitting form of MS than in ethnically homogeneous controls. Restriction fragment length polymorphism analysis by Southern blotting of the C4/CYP21 gene complex showed that a structural gene deletion was present in 45% of patients with the C4AQ0 allele. Our data support the hypothesis that relapsing-remitting MS and primarily chronic progressive MS are immunogenetically distinct diseases; further, complement factor abnormalities typical of autoimmune diseases could influence the pathogenesis of MS.

Case-Control Studies↗

PubMed1989

Lack of a role of monocytes in the inhibition by monoclonal antibodies to monomorphic and polymorphic determinants of HLA class I antigens of PHA-P-induced peripheral blood mononuclear cell proliferation.

This study aimed at characterizing the mechanism(s) underlying the regulatory role of distinct determinants of HLA Class I antigens in PHA-P-induced T cell proliferation and the involvement of monocytes in this phenomenon. The anti-HLA-A2,A28 monoclonal antibodies (MoAb) CR11-351, the MoAb Q6/64 to a determinant restricted to the gene products of the I antigens HLA-B locus, and the MoAb CR10-215 and W6/32 to distinct monomorphic determinants of HLA Class I antigens were found to inhibit PHA-P-induced peripheral blood mononuclear cell (PBMC) proliferation in a dose-dependent fashion. The inhibition is specific and reflects neither inhibition of PHA-P binding to cells nor a toxic effect of the anti-HLA Class I MoAb. The latter differed in the concentration required to induce inhibition, in the influence of the concentration of PHA-P used as mitogen, in the differential effect on the donors used as a source of PBMC, and/or in the requirement of the Fc portion to induce inhibition. At variance with the information in the literature, the inhibitory effect of anti-HLA Class I MoAb on PHA-P-induced PBMC proliferation neither reflected their interaction with accessory cells nor was mediated by suppressor factors released by monocytes stimulated with PHA-P in the presence of anti-HLA Class I MoAb. Therefore, the regulatory role of HLA Class I antigens in T cell proliferation is not likely to be mediated by monocytes and/or factors released from them, but may reflect an involvement of these molecules in T cell activation pathways.

Antibodies, Monoclonal↗