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At least 973 records · Page 54Linked to original sources
PubMed2003

HLA points assigned in cadaveric kidney allocation should be revisited: an analysis of HLA class II molecularly typed patients and donors.

The points now assigned for the quality of HLA match have received significant scrutiny to be modified in an effort to help reduce disparity in access to kidneys of minority groups, and since differences in graft survival between groups of patients in each of the HLA matched groups is less now than in the past. We analyzed long-term (5-year) graft survival in 746 DR DNA typed recipients of cadaveric kidneys transplanted from 1994-2001 whose donors were also DR DNA typed, with allocation based on those DNA-based typings. Five-year graft survival was not significantly different for recipient groups irrespective of if they had zero (84%), one (92%), two (89%), or three to four B, DR mismatches (79%) (log-rank = 0.15; died with a functioning graft [DWFG] censored). Mismatching of three and four DR and DQ antigens in black but not white patients was associated with significantly worse survival (Relative Risk = 2.9) (p = 0.002). The incidence of minority transplants in the well-matched group (zero and one B, DR mismatch), 12.8% (20/156) was over half that of the less well-matched group, 27.1% (160/590) (p < 0.001). Our data indicate that the current HLA-B, DR-based point system used to allocate kidneys warrants re-evaluation. Our data, taken in the context of the UNOS data, which has recently been re-evaluated, suggest that the only HLA-DR remain as a component of the national kidney allocation algorithm so as to increase access of kidneys to minorities and minimize graft loss.

Cadaver↗
PubMed1990

Ultraviolet B-induced loss of HLA class II antigen expression on lymphocytes is dose, time, and locus dependent.

Ultraviolet B (UVB) irradiation interferes with the afferent and efferent loops of the immune response. One mechanism that has been suggested is the decline of class II histocompatibility antigen expression on the cell surface. However, data in the literature are controversial. In the present study, we examined the effect of UVB light (peak emission at 302 nm), at doses of 0.05-300 mJ/cm2, on class II antigen expression on normal peripheral blood lymphocytes enriched for non-T cells. Monoclonal antibodies directed at nonpolymorphic determinants on HLA-DR, -DQ, and -DP were used to label cells before and at time intervals up to 72 h after irradiation. Immediately following UVB exposure, fluorescence intensity for all three antigens was equal to or slightly increased above control values. Subsequently, there was a decline in antigen expression that was UVB dose dependent and varied for HLA-DR, -DP and -DQ. Although there was only a very moderate loss of surface labeling for HLA-DR up to 72 h, there was a steep decline for HLA-DQ and -DP. There was no significant decline in class II antigen expression on cells exposed to 2000 or 4000 cGy of gamma irradiation. Also, there was no effect of either gamma or UVB irradiation on class I antigen expression. These data explain some of the discrepancies in previous reports on the effects of UVB on class II antigens; they show not only a dose effect but also an effect of time after exposure and, most importantly, the class II antigen under study.

Dose-Response Relationship, Radiation↗
PubMed1984

Identification of a sulfate-bearing molecule associated with HLA class II antigens.

The human Ia antigens (DR, DS, and SB), determined by genes contained within the HLA complex on chromosome 6, are glycoprotein heterodimers consisting of a Mr approximately equal to 34,000 alpha chain and a Mr approximately equal to 28,000 beta chain. As a result of studies exploring the possibility that alpha or beta (or both) might be sulfated, a unique component of the oligomeric Ia antigen complex was discovered. When anti-Ia immunoprecipitates from Nonidet P-40 lysates of [35S]sulfate-labeled lymphoid cells were analyzed by NaDodSO4/PAGE, a molecule of considerable size heterogeneity (Mr 40,000-70,000) was observed. This component was present in both anti-DR and anti-DS immunoprecipitates prepared from both human tonsil cells and lymphoblastoid B-cell lines but was not observed in control precipitates or in association with immunoglobulin or class I HLA molecules. Preliminary biochemical studies indicate that this Mr 40,000-70,000 molecule is polyanionic, disperse in molecular weight, and sensitive to protease digestion. The sulfate-bearing moiety of this component was resistant to Pronase but sensitive to chondroitinase ABC, indicating that this molecule belongs to the chondroitin sulfate class of proteoglycans.

Adolescent↗
PubMed1992

Genetic analysis of HLA class II alleles and susceptibility to type 1 (insulin-dependent) diabetes mellitus in Japanese subjects.

Although HLA-DQB1 alleles encoding aspartic acid at position 57 (Asp-57) are protective against Type 1 (insulin-dependent) diabetes mellitus in Caucasians, most Japanese Type 1 diabetic patients carry at least one Asp-57 DQB1 allele. We analysed the DRB1, DQA1 and DQB1 genes of 99 Japanese patients and 86 control subjects with polymerase chain reaction and sequence-specific oligonucleotide hybridization. We found that (1) the DQA1*0301 allele was significantly increased in Type 1 diabetic patients (RR7.8, pc less than 0.0001); (2) the DRB1*0405 (Dw15) allele, which is a subtype of DR4 haplotype, was significantly increased in DR4-positive patients (RR 12.0, pc less than 0.001); and (3) although the DRw8-DQw8 haplotype was positively associated with Type 1 diabetes, the DRB1*0406-DQw8 haplotype was decreased in the diabetic patients. These data indicate that DRB1 and DQA1 genes also confer susceptibility to Type 1 diabetes in Japanese.

Alleles↗
PubMed1988

HLA class II genes polymorphism in DR4 giant cell arteritis patients.

We have previously reported a significant increase of HLA-DR4 antigen frequency in giant cell arteritis (GCA). This finding suggested an important role of immunogenetic factors in this syndrome. Recent data suggest that inherited susceptibility to several autoimmune diseases was associated with specific DR4 associated DQ beta alleles. DNAs from 27 DR4 positive patients with GCA were digested with Taq I and Bam HI, analysed on 0.7% agarose gel and hybridized with DR beta, DQ alpha and DQ beta probes. DR beta hybridization produced no variant detectable within DR4. DQ beta probe confirmed two clusters among DR4 associated DQW3 alleles: DQW 3.1 (Bam HI 360 Kb) and DQw 3.2 (Taq I 1.9 Kb and Bam HI 11 Kb). Among our 27 DR4 positive patients, 34% were DQW 3.1 and 66% were DQW 3.2. These frequencies are the same as those observed in healthy controls.

DNA↗
PubMed1993

Identification of unrelated HLA-identical bone marrow donors: RFLP, oligotyping and PCR fingerprinting for HLA class II compared to MLC responses.

22 patients awaiting bone marrow transplantation (BMT) and 65 unrelated healthy HLA-A, B and DR serologically identical donors were studied. 21 patients were non reactive on mixed lymphocyte culture (MLC) towards at least one BMT donor, resulting in 32 pairs MLC-negative. 33 other HLA-matched donors gave proliferative responses on MLC. The phenotype DR3/DR7 was significantly higher in patients (P) and donors (D) studied (p < 0.00001). P and D pairs were DNA typed by RFLP analysis for DRB, DQA and DQB genes, and DNA matched by PCR Fingerprinting (PCRF) for DRB, DQA, DQB and DPB. Six patients and 18 donors were also oligotyped for the subtypes of DR1, DR3, DR4 and DR5. Patients and donors were divided according to identity on RFLP, PCRF and responsiveness on MLC, represented by RRI. In the group of MLC non responder pairs, 11% had differences on DRB PCRF compared to 57% in the group of MLC responders (p = 0.0002). The mean RRI value of PCRF DRB incompatible pairs was significantly higher compared to RRI of compatible pairs (p = 0.012). With respect to PCRF for DPB, 75% of MLC-ve pairs were different. Also the mean RRI value was significantly lower in DPB identical pairs compared to non identical ones (p = 0.048). The compatibility between P/D pairs assessed by oligotyping was in accordance with DRB PCRF. PCRF for DQB, but not for DQA, corresponded to MLC responses. Our findings confirm that PCRF offers a precise and fast alternative in DNA matching for DRB. We also suggest that PCRF for DQB and DPB, together with DRB, could eventually substitute MLC.

Bone Marrow Transplantation↗
PubMed1999

Strong association of HLA class II sequences in Mexicans with Vogt-Koyanagi-Harada's disease.

Vogt-Koyanagi-Harada's syndrome (VKH) is an autoimmune disease prevalent in Mongoloids with evident participation of HLA. The aim of this study was to identify the class II DNA sequences involved in the etiopathogenesis of VKH in Mexican Mestizos. This study included 46 VKH patients and 170 controls. 75% were females (mean age at onset of 33.5 years). The disease evolved to chronicity (68%) and 25% of the patients were unresponsive to corticotherapy. DNA typing of HLA-DRB1, DQA1 and DQB1 was done following the 12th International Histocompatibility protocols. VKH was strongly dependent of DRB1 gene; DRB1*04 was found in 78.2% of the patients vs. 50.6% of the controls (p = 0.001). No particular DRB*04 subtype was significantly increased, suggesting that residues E-9 V-11; H-13; H-33 and Y-37 shared by all DR4s are implicated in susceptibility to VKH. However DRB1*0101 (p = 0.009, OR = 4.2) was clearly associated. This allele shares the motif LLEQRRAAG located at position 67-74 and 86 of DRB1 with *0405 associated in Japanese. Two HLA associated mechanisms may be triggering the autoimmune phenomena. One involving critical polymorphic residues expressed in different alleles. Secondly, some peptides may anchor to the conserved residues leaving other sequences to bind to the T cell receptor.

Adult↗
PubMed1986

Structure and evolution of the HLA class II SX beta gene.

The class II major histocompatibility complex antigens are cell-surface heterodimers consisting of an alpha and a beta chain. Cosmid cloning has shown that the three families of class II antigens, DR, DQ, and DP, are encoded within the HLA-D region of chromosome 6 as a series of discrete gene clusters. The DP cluster contains two pairs of alpha and beta genes, one of which encodes the biochemically-defined DP antigen. In order to assess whether the other two genes, SX alpha and SX beta, are also expressed, potential coding regions have been subcloned and sequenced. The SX3 beta gene is shown to contain regions closely homologous to all six exons of DP beta. A 1 bp deletion in the beta 2 exon, also observed for the SX4 beta allele, causes a translational frameshift, suggesting that SX beta is a pseudogene. However, all the other exons, as well as their splice sites and the putative promoter region, appear to be intact.

Alleles↗
PubMed1995

Characterization of three separated exons in the HLA class II DR region of the human major histocompatibility complex.

The human major histocompatibility complex, HLA, is a highly polymorphic gene region which includes the DRA and DRB genes. The number of DRB genes differs between haplotypes. The DR4 haplotype seems to be one of the most complex with five DRB loci, DRB1, DRB4, DRB7, DRB8, and DRB9, in addition to the single DRA locus. We determined the nucleotide sequences of three separated DRB exons located between the DRB4 locus and the DRA locus in the DR4 haplotype, two DRB signal-peptide exons (S1 and S3) and one DRB first-domain exon (locus designation DRB9). Sequence comparisons suggest the following order of events for the origin of these exons: DRB9 seems to be the oldest exon and has previously been detected in multiple HLA haplotypes. DRB9 is more divergent than the three other known DRB pseudogenes, all of which have been found in apes. This suggests that DRB9 arose prior to the hominoid divergence. An L1 repeat has been inserted 3' to DRB9. Subsequently, a LTR of the ERV9 retrovirus-like family was inserted into the L1 repeat. Such LTRs have recently been observed in some of the other DRB genes. The pseudogenes DRB7 and DRB8 (containing only exons 3-6) arose after DRB9. Finally, the separated signal peptide exons S1 and S3 were formed. The molecular characterization of these separated DRB exons and insertion elements further clarifies the complex evolutionary history of the HLA-DR region. These selectively neutral exons may serve as useful markers for tracing the phylogeny of HLA haplotypes.

Base Sequence↗
PubMed1998

Predictive value of HLA class II PCR typing for the outcome of mixed lymphocyte reaction.

The use of HLA-DRB1 and -DQB1 polymerase chain reaction-sequence-specific primer (PCR-SSP) typing at different levels of resolution for MLR prediction was assessed in 54 HLA-A and -B matched donor/recipient unrelated pairs and 89 HLA-A and -B identical siblings. Graft-versus-host (GvH) direction one-way MLR was evaluated unless stated otherwise. The typing of DRB1 alleles satisfactory for MLR prediction in HLA identical siblings (P = 0.0015) does not appear to be sufficient in matched unrelated pairs (P = 0.2407). Using more discriminatory PCR-SSP typing, the disparity in DRB1 allelic subtypes was predominantly found in the category of DRB1 allele compatible, MLR positive unrelated pairs. Besides, DRB1 allelic subtype mismatches were revealed in five of the forty-one DRB1 allele compatible, MLR negative unrelated pairs. More discriminatory typing made the correlation between DRB1 compatibility and MLR negativity extremely significant (P = 0.0001). As for these five exceptional cases, the reciprocal host-versus-graft (HvG) direction MLR was considered, too. This allowed HLA-D disparity to be disclosed in two of them. An uninterpretable result reflecting defective MLR reactivity occurred in one case. Negative reciprocal MLR in the last two DRB1 allelic subtype incompatible pairs is hardly to explain without postulation of MLR silent DRB1 allelic subtype mismatches. An analysis in unrelated pairs showed a role of some DQB1 gene products in the proliferative response too. GvH direction positive MLR was found in two HLA identical siblings among the 89 tested. The DPB1 incompatibility detected in one of them could be a potential cause of proliferative response but MLR reactivity in the other, DPB1 identical, pair cannot be interpreted easily.

Alleles↗
PubMed2000

HLA class II genotypes in Mexican Mestizos with familial and nonfamilial multiple sclerosis.

Predisposition to MS is associated with the HLA-DR2 antigen in white patients. The authors investigated the genetic factors behind the increasing frequency of MS in the Mexican population. HLA-DR and DQ were analyzed in 17 patients with MS, 15 of their first-degree relatives, and 99 healthy ethnically matched controls. DR2 or DR3 was found in 15 of 17 patients. In controls, both alleles had frequencies less than 0.05. MS in Mexican patients was associated with HLA-DR2 and DR3.

Adult↗
PubMed2000

Relationship between the occurrence of anti-SSA, anti-SSB autoantibodies and HLA class II alleles from the aspect of in vitro inhibitory effect of glucocorticosteroid on the antibody-dependent cellular cytotoxicity in patients with primary Sjögren's syndrome.

Though at present there is no evidence-based algorithm for the treatment of primary Sjögren's syndrome, it is generally accepted that glucocorticosteroid (GS) therapy must be introduced in cases with severe systemic manifestations. As the side-effects of the GSs are well known, it would be useful to know in advance how the patients will respond to this type of treatment. For this reason we measured the in vitro steroid sensitivity of 29 SS patients using inhibition of antibody dependent cellular cytotoxicity (ADCC) test by methylprednisolone compared to that of 28 controls. SS patients proved to be significantly less sensitive to GSs than controls (inhibition of ADCC reaction: 42.4 vs 53.1%; p < 0.01). This was especially true in SS patients with anti-SSA and/or SSB autoantibody positivity and with HLA-DR2 and/or -DR3 alleles. Comparing the results of the in vitro GS sensitivity and the clinical effectiveness of the previously applied corticosteroid therapy it seems that steroid inhibition of ADCC reaction has a predictive value in determination of in vivo sensitivity to GSs. However, in patients with decreased in vitro GS sensitivity a more expressed in vivo steroid sensitivity cannot be excluded.

Adult↗
PubMed2004

HLA class II haplotypes in Mexican systemic lupus erythematosus patients.

Systemic lupus erythematosus (SLE) is an autoimmune disease in which polymorphisms within the human leukocyte antigen (HLA) region have been associated to its etiology. For this study, HLA-DQB1, DQA1, and DRB1 genes were typed by polymerase chain reaction-sequence-specific primer in 237 individuals, taken from 74 families, who had a member with SLE, and who had their residence in the western region of Mexico; as well as in 159 ethnically matched healthy volunteers taken from 32 families. Genotype and allele frequency analysis was performed in 74 SLE patients and 54 unrelated controls. Precise three-loci identification of independent haplotypes was performed in 48 patients and 54 controls by familial segregation. Genotype distribution at each loci was concordant with Hardy-Weinberg's equilibrium in the control group. In general, no genotype effect was observed in SLE patients. Allele distribution comparison showed in the SLE group a significant increase of HLA-DQA1*0102, DQB1*0402, and DRB1*15; whereas alleles HLA-DQB1*0303 and *0501 were significantly decreased. SLE patients showed haplotype DQB1*0602-DQA1-*0102-DRB1*15 increased. As expected, patients with SLE have a reduced haplotype genetic diversity. The associations found in this study are related to an ancestral haplotype that has been observed in SLE populations of different origins.

Adolescent↗