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E D Albert

Publications and source records attributed to E D Albert.

At least 55 records · Page 3Linked to original sources
PubMed1996

Strong association of dermatomyositis-specific Mi-2 autoantibodies with a tryptophan at position 9 of the HLA-DR beta chain.

OBJECTIVE: To characterize the clinical and immunogenetic features of patients with Mi-2 autoantibodies. METHODS: Eighteen adult white patients with Mi-2 antibodies were clinically characterized and compared with 41 Mi-2-negative dermatomyositis (DM) patients. HLA class I and class II typing for DRB alleles was done by microcytotoxicity assay and for DQA and DQB alleles by polymerase chain reaction-based oligotyping. RESULTS: Seventeen of the 18 Mi-2-positive patients had DM. Symptoms of scleroderma, lung involvement, and arthritis were less common in this group than in the Mi-2-negative DM patients; the V-sign rash and nailfold involvement were found more frequently. Mi-2 antibodies were strongly associated with HLA-DR7 (88% versus 24% in healthy controls), HLA-DQA1*0201 (86% versus 23%), and DR7 "homozygosity" (31% versus 0%). A tryptophan residue at position 9 of the HLA-DR beta chain was present in all Mi-2-positive patients (100% versus 62%; homozygous in 81% versus 15%). CONCLUSION: Our results reemphasize the specificity of Mi-2 antibodies for DM, and extend previous reports that Mi-2 antibody production is associated with certain HLA class II antigens. We propose beta 9-Trp as a candidate epitope on the HLA-DR beta chain as a prerequisite for this type of autoimmune response.

Adenosine Triphosphatases↗
PubMed1995

Sequence polymorphism in the HLA-B promoter region.

Transcription of major histocompatibility complex class I genes is controlled by the class I regulatory complex in the 5' flanking region. To investigate the molecular basis of this region, we studied the polymorphism of the promoter of the HLA-B locus extending from the ATG transcription initiation signal to -284 base pairs (bp) which includes a number of cis-acting elements: interferon response sequence (IRS), enhancer A and enhancer B. Genomic DNA from 35 homozygous cell lines from the 10th International Histocompatibility Workshop and from eight heterozygous panel members was amplified using two primers designed to specifically amplify the HLA-B locus. The double-stranded polymerase chain reaction products were sequenced using the cycle sequencing technique and an ABI 373A automatic sequencer. Promoter sequences of thirty-one different HLA-B alleles were determined in this study. Within the 284 bp upstream of the ATG signal, base substitutions were observed in 23 different nucleotide positions. Our study shows a high degree of polymorphism of the HLA-B promoter region, but conserved sequences of the known cis-acting elements with the exception of enhancer B in which there are two base substitutions for B7 and B42 (position -93 and position -95). The 23 polymorphic sites can be grouped into 12 different HLA-B promoter types (groups A to M) for 31 HLA-B locus alleles. Some of the groups of alleles sharing the same promoter sequence such as, for example, group A with B51, B52, B53, and B35, might have been predicted on the basis of serological similarity and/or exon 2, 3 sequence. In other groups, such as G (B18, B37, B27), it could not have been anticipated from serological experience that B18 and B27 carry the same promoter. Several sequencing errors were detected in the HLA-B promoter sequences published previously.

Alleles↗
PubMed1995

Immunoprinting: various genes are associated with increased risk to develop rheumatoid arthritis in different groups of adult patients.

To identify genes that contribute to the manifestation of rheumatoid arthritis we performed association studies via microsatellite analyses of immunorelevant loci (HLA-DRB, 5 T cell receptor loci, TNFa IL1, IL2, IL5R and CD40L). A total of 183 patients and 275 healthy controls were typed in terms of HLA and grouped according to the known predisposing HLA-DRB1 genes (DRB1*04; relative risk approx. 5; DRB1*01, relative risk approx. 2; a third group carried neither allele). Microsatellite polymorphisms characterizing the TCRBV6S3, CD3D, IL1A, IL2, and IL5R genes did not show significant associations with rheumatoid arthritis, whereas TCRBV6S1, TCRBV6S7, TNFa, and CD40L genes may influence relative protection or risk in certain groups of patients. Analysis of a microsatellite marker adjacent to the transcription element alpha (TEA) in the T cell receptor alpha delta complex indicates that in the cohort carrying neither the DRB1*04 nor the DRB1*01 allele the relative risk to acquire rheumatoid arthritis is increased (> 13) or decreased (< 0.07), depending on the inherited microsatellite allele adjacent to the TEA locus. Sequence analysis of the closely linked TEA region from patients and controls revealed a novel dimorphism. Only the newly identified TEA allele leads to binding of a nuclear protein that may be involved in the regulated expression of the TCRDA genes. Subsequent typing of rheumatoid arthritis patients and controls revealed, however, that the association of the microsatellite marker is largely independent of the TEA allele, confirming incomplete linkage in the 2 kb region of the TCRDA locus. These results are discussed in the context of hot spots of recombination in this genomic region and other linked candidate sequences that predispose to develop rheumatoid arthritis.

Alleles↗
PubMed1995

Identification of two major HLA-B44 subtypes and a novel B44 sequence (B*4404). Oligotyping and solid phase sequencing of polymerase chain reaction products.

PCR-based analyses were performed for the identification of HLA-B44 subgroups. Genomic DNA from six homozygous cell lines and 44 healthy individuals who had serologically tested positive for HLA-B44 was investigated for polymorphism in exons 2 and 3 of the HLA-B44 genes. Two primers were designed for specific amplification of the B*4401 allele in exon 2. None of the tested genomic DNAs, including the cell line "BAU-J" from which the sequence of B*4401 was derived, was amplified successfully using these primers, indicating that the B*4401 sequence may not be correct in position 242-244. For identification of the B*4402 and *4403 subtypes we specifically amplified the B44 gene in exon 3 using two sequence-specific primers. The PCR products, which were obtained from all B44-positive samples (n = 50) and from none of the B44-negative controls (n = 20), were subsequently hybridized with the dig-ddUTP-labeled oligonucleotides. The base substitution at position 146, as described previously for B*4401 and *4402 (C for G), could not be confirmed by oligonucleotide hybridization. In contrast, the oligonucleotide typing for G in position 146 gave positive signals in all B44-positive samples. Except for one, HLA-B44-positive DNAs from LCLs and healthy individuals could be divided into two subgroups according to the polymorphic region in position 195-197. Out of 44 unrelated individuals with B44, 27 (61%) were positive for B*4402 and 16 (36%) were positive for B*4403.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗
PubMed1995

Early-onset pauciarticular juvenile chronic arthritis is associated with a mutation in the Y-box of the HLA-DQA1 promoter.

Early-onset pauciarticular juvenile chronic arthritis (EOPA-JCA) has associations with different alleles of the MHC region (HLA-A2, DR5, 6, 8, DQA1*0401, *0501, *0601 and DPB1*0201). All susceptible DQA1 alleles carry an exclusive sequence motif. MHC-class II gene expression is controlled by 5' flanking upstream regulatory regions (URR). A hypervariable region in the promoter region of the HLA-DQA1 gene (-240 and -200 base pairs upstream) defines ten different QAP (DQA1-Promoter) alleles, which are associated with certain DQA1-alleles. The Y-Box in the DQA1 promoter (YC-Box -125 to -115 upstream from the ATG) differs from the consensus sequence (-123 A for G) of all other MHC class II Y-Boxes, resulting in a lower affinity to the NF-Y transcription factor and in a reduced expression of DQA1. A second substitution in the Y-Box of QAP 4.1 and 4.2 (-119 A for G) is found in the promoter alleles of the DQA1-alleles (DQA1*0401, *0501, *0601) and is strongly associated with susceptibility to EOPA-JCA.

Age of Onset↗
PubMed1994

HLA class II genes and antibodies against recombinant U1-nRNP proteins in patients with systemic lupus erythematosus. SLE Study Group.

To investigate a possible involvement of HLA-class II alleles in the genetic predisposition for the formation of anti-U1-nRNP antibody-in systemic lupus erythematosus (SLE), genomic DNA of 178 patients was typed for the DRB1, DQA1 and DQB1 alleles using a polymerase chain reaction (PCR) and non-radioactive-oligonucleotide typing. Antibodies against recombinant U1-nRNP proteins (U1-A-, U1-C- and 70K-protein) were determined by ELISA. Anti-U1-C antibody was found in 26 (14.7%), anti-U1-A in 34 (19.2%) and anti-70K in 17 (9.6%) patients. A joint occurrence was observed for these antibodies against the recombinant U1-nRNP proteins: anti-U1-C and anti-U1-A antibodies occurred together more frequently than alone and than together with anti-U1-70K antibodies. The frequency of DRB1*04 was slightly increased in the patients with anti-U1-C as compared to the patients without anti-U1-C (P < 0.05, Pcorr = n.s., RR = 2.4). The DQA1*0301 allele, which is in linkage disequilibrium with DRB1*04, is found more frequently in anti-U1-C-positive than in antibody-negative patients. The DQB1*0303 allele, detected in 12 of 176 SLE patients, was absent in the patients with any of the antibodies against the U1-nRNP proteins. All these deviations may be due to chance alone. We concluded that the presence of antibodies against recombinant U1-nRNP proteins was not significantly associated with any HLA DRB1, DQA1 and DQB1 allele in our group of SLE patients.

Alleles↗
PubMed1994

Susceptible and protective major histocompatibility complex class II alleles in early-onset pauciarticular juvenile chronic arthritis.

Oligonucleotide typing for alleles of the MHC loci DRB1, DQA1, and DQB1 was performed in 160 patients suffering from EOPA, JCA (or JRA = juvenile rheumatoid arthritis). Allele and haplotype frequencies of the patients were compared with the data of an unrelated healthy control group consisting of 200 individuals. Analysis of frequencies shows that HLA alleles are associated not only with susceptibility to EOPA-JCA but also with protection from the disease. The presence of protection connected with certain HLA alleles was assessed using a calculation which takes into account the condition that if one allele is increased, all other alleles of the same locus must be decreased in compensation. Protection can be assumed only in cases where a given allele has an observed frequency which is significantly beyond the expected compensatory decrease. Thus a hierarchy of associations was observed in EOPA-JCA patients. The alleles of the haplotypes DRB1*11 (12)-DQA1*0501-DQB1*0301 as well as DRB1*08-DQA1*0401-DQB1*0402 were found to be associated with susceptibility to disease, whereas the alleles DRB1*07 and DQA1*0201 converge with significant protection from the disease. Whereas the association with disease susceptibility seems to depend on a sequence motif encoded in certain DQA1 alleles, protection is associated either with alleles of DRB1 or DQA1.

Alleles↗