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A Corell

Publications and source records attributed to A Corell.

50 records · Page 3Linked to original sources
PubMed1991

The HLA-DRB6 locus defines an evolutionary supratypic group within the DRB family of genes.

A novel DRB gene member has recently been identified (DRB6). It defines a new supratypic group of HLA-DR alleles comprising the DR1-, DR2-, and DRw10-carrying haplotypes. The comparison of this gene either at the nucleotide or at the protein level with other HLA-DRB genes supports its inclusion in the DRB gene family and not in DPB or DQB gene families. Moreover, the construction of an evolutionary gene-tree shows that this gene is probably the eldest member of the DRB gene family. Contradictory expression results do not clarify whether or not DRB6 is a pseudogene.

Base Sequence↗
PubMed1991

Exclusive HLA-DQ factors do not explain susceptibility to insulin-dependent diabetes.

DQA1, DQA2, DQB1, and DRB1 alleles have been determined and the DQA1 and DQB1 DNA gene sequences assigned by using restriction fragment length polymorphisms in 67 diabetic individuals and 72 controls. It has been found that: 1) DQA2 (U allele) is not a susceptibility factor, 2) non-aspartic acid homozygosity in residue 57 (Asp 57 negative) of the DQ beta chains is positively correlated with insulin-dependent diabetes mellitus (IDDM), and 3) DQ beta Asp-57-negative and DQ alpha arginine-52-positive (Arg-52-positive) individuals are increased among diabetic patients; this latter analysis shows a higher etiologic fraction (delta) value than the one obtained when considering only homozygous DQ beta Asp-57-negative individuals. However, if only non-DR3 or DR4 individuals were considered (both in DQ beta Asp-57-negative homozygous and in DQ beta Asp-57-negative/DQ alpha Arg-52-positive individuals) the correlation with disease disappears. In addition, the postulated risk DQ beta Asp 57-negative and DQ alpha Arg 52 positive is absent in six patients. These data do not discard the possibility that DR3/DR4 may contain the primary susceptibility factors. It is concluded that it is not possible to assign the susceptibility to IDDM to a specific HLA locus and that several loci within the same or the trans haplotype may be involved.

Alleles↗
PubMed1991

High frequency of the HLA-DRB1*0405-(Dw15)-DQw8 haplotype in Spaniards and its relationship to diabetes susceptibility.

A study of DR4 subtypes has been done in Spanish unrelated controls and insulin-dependent diabetics by using dot blot hybridization with specific DR4B1 exon-2 oligonucleotides and automated dideoxy DNA sequencing. Dw15-DQw8 is the predominant DR4 subtype present in our normal population (37%); this DR4 frequency characteristic singles out our population from all other Caucasoids tested so far and may also be a marker of the original Iberian paleo-North African population. Dw15-DQw8 is not significantly increased in our insulin-dependent diabetics sample and despite its relative high frequency in the control population it does not have a bearing in lowering insulin-dependent diabetes mellitus frequency of DR4-positive Spaniards. In addition, no particular DR4 split is by itself significantly increased in Spanish diabetics; this may indicate that selective diabetogenic environmental factors may be working upon DR4-positive individuals, but on genes (or gene products) other than DR or at least not upon the polymorphic sites of DRB1 exon-2 products.

Amino Acid Sequence↗
PubMed1991

C4 Chido 3 and 6 distinguish two diabetogenic haplotypes: HLA-B49, SC01,DR4,DQw8 and B8,SC01,DR3,DQw2.

The combination of the HLA complement allotypes BFS, C2C, C4AQ0 (deleted gene) and C4B1, termed SC01 complotype, usually present in the HLA-B8,DR3,DQw2 diabetogenic haplotype, has also been found in a novel "low frequency" HLA-B49,DR4,DQw8 haplotype associated with Spanish insulin-dependent diabetes mellitus (IDDM). Family studies of C4 antigenic determinants Rodgers/Chido and their specific C4d nucleotide sequences confirm that this novel haplotype bearing Chido -3, -6 is not due to a recent recombination from the common HLA-B8,DR3 haplotype bearing Chido 3,6; moreover, Chido analysis at the serological or DNA level is presently the only way to distinguish both SC01 complotypes, since BF, C2, steroid 21-hydroxylase and C4 genes do not reveal other differences by restriction fragment analysis. On the other hand, HLA-B49,SC01,DR4 is the first DR4-bearing IDDM-susceptible haplotype with a deleted C4 gene described so far and the only DR4-bearing haplotype found in the Spanish population. This report further supports the fact that extended haplotypes with deleted (or "not duplicated") genes in the class III region contain IDDM-susceptibility more often than non-deleted (or "duplicated") haplotypes in the Spanish and other Mediterranean populations.

Base Sequence↗
PubMed1990

Both HLA class II and class III DNA polymorphisms are linked to juvenile rheumatoid arthritis susceptibility.

HLA-DR5 and DRw8 are not significantly linked to juvenile rheumatoid arthritis (JRA) in the Spanish population. However, we have found restriction fragment length polymorphisms (RFLPs) beta DR-2.9-kb-EcoRI and C4-14.3-kb-EcoRI, that correlate significantly with JRA. Eighty-six percent of our patients present either HLA-DR5 or the beta DR-2.9-kb-EcoRI allogenotope or lack the C4-14.3-kb-EcoRI allogenotope compared to 48% in controls; however, these particular DR and C4 RFLPs may not represent the corresponding DRB1 or C4 genes but rather neighboring ones which may be relevant to confer JRA susceptibility. The C4-14.3-kb-EcoRI RFLP decrease in patients may reflect a decrease in C4 B "long" phenotypes. Also, both RFLPs are the only markers able to identify most of the JRA patients in our population. On the other hand, the findings of both class II and III genes associated to JRA may reflect the existence of epistatic interactions (cis or trans) within the HLA gene cluster which lead to a particular pathology in certain diseases.

Arthritis, Juvenile↗
PubMed1990

Exon 2 DNA sequence of the HLA-DRw13b allele obtained from genomes of five different individuals.

Exon 2 nucleotide sequence of the DRB1 gene encoding the HLA-DRw13b allele defined by DNA-RFLP (Restriction Fragment Length Polymorphism) typing, has been obtained by using five heterozygous individuals genomic DNA and a non isotopic automated "dideoxi" methodology. Its comparison with other known homologous DRB1 sequences suggests that two different mechanisms which generate HLA allele variability may have occurred in this particular exon 2: a gene conversion between DRw11 or DRw13 as acceptors and DR4-Dw15 or DRw8.1 as donors and in addition, a non-conservative point mutation at base 221. The relationship between this HLA sequence characteristics and certain diseases susceptibility is discussed.

Alleles↗
PubMed1990

Shared SstI RFLPs by HLA-Aw19, A23/24 and A3/11 crossreacting groups.

Three novel restriction fragment length polymorphisms (RFLPs) have been identified using a pan-HLA class I probe and the endonuclease SstI. This study, in conjunction with previously reported SstI RFLPs, now allows the identification of the HLA-crossreacting antigens Aw19 (A29/30/31/32/w33), A23/24 and A3/11 by specific hybridization patterns with a single enzyme/probe combination. Three of the corresponding polymorphic SstI restriction sites map within the HLA-A gene and generate two allelic RFLPs (5.06, 5.92 kb) and one single RFLP (5.92 kb) that show an absolute correlation with HLA-A23/24 and A29/32 crossreacting antigens, respectively. However, other SstI RFLPs (7.97, 9.4, 9.6, 9.8 and 13.34 kb), also linked to HLA-A crossreacting antigens, map outside the HLA-A gene and probably correspond to non-HLA-A,B,C class I genes in strong linkage disequilibrium with the HLA-A gene. These data show that HLA-A crossreacting antigens share more SstI RFLPs than neighboring non-HLA-A,B,C class I genes or pseudogenes; also, this has raised the possibility that some crossreacting HLA-A alloantisera might additionally recognize shared antigenic determinants in non-HLA-A,B,C proteins since the HLA-Aw19 crossreactivity cannot be fully explained by analyzing the HLA-A amino acid sequence.

Chromosome Mapping↗
PubMed1989

An Eco RI polymorphic site in the human complement C4 gene distinguishes juvenile rheumatoid arthritis (JRA) susceptibility-bearing haplotypes.

Susceptibility to acquire Juvenile Rheumatoid Arthritis (JRA) is linked to HLA-DR5 and DRw8 antigens in Caucasoid populations. However, the frequency of HLA-DR5 is too high in the normal Spanish population and JRA cannot thus be found to be associated with this antigen. It has been found a 14.3 kb-C4-Eco RI restriction fragment length polymorphism which correlates significantly with JRA and may be used as a marker for this disorder in Spaniards.

Arthritis, Juvenile↗
PubMed1987

An in vivo functional immune system lacking polyclonal T-cell surface expression of the CD3/Ti(WT31) complex.

A polyclonal T-cell receptor complex (TCR) expression defect (as detected with monoclonal antibody WT31) has been found in two children belonging to an otherwise healthy Spanish family. One of the sibs (V, who had been vaccinated with attenuated poliomyelitis virus) showed clinical signs of immunodeficiency with an autoimmune syndrome, but the other (older) sib (D, vaccinated with attenuated rubella, measles, mumps, and poliomyelitis viruses) has been symptomless throughout life. In contrast to both sibs' normal expression of other peripheral leucocyte markers, as measured by flow cytometry (including CD1, CD2, CD4, CD8, and CD16), only about 6% of CD2+ polyclonal T cells expressed surface antigen-specific T-cell receptor (Ti/WT31), and only about 23% weakly expressed surface CD3 determinants. On the remaining CD2+ T cells in each sib the expression of Ti and CD3 was undetectable; the defect in CD3 expression is very likely secondary to the defect in Ti expression. Natural killer (NK) activity was not increased in any of the sibs, ruling out a high content of NK cells among their CD2+ lymphocytes. Functional data indicate that CD3-mediated T-cell activation with anti-CD3 monoclonals and Ti-mediated responses to allogeneic and tetanus toxoid antigens were severely depressed, whereas activation via CD2 was normal in the T lymphocytes of both sibs. Genes encoding for Ti alpha, beta, and gamma chains did not show major alterations by southern blot analysis, and polyclonal beta chain genes rearrangements were detected in both children's T-cell blasts. Family clustering suggests a genetic pathogenesis, but linkage to HLA or other blood group markers has not been found. Sib V had a concomitant autoimmune disease and died after a severe autoimmune haemolytic anaemia, indicating a relationship between the TCR and generation of autoimmune clones. However, the resistance of both individuals to infection and to vaccination with attenuated viruses, and the fact that sib D has been symptomless to date questions the relative importance of the TCR in the immune response against infection, and suggests that alternative T-cell activation pathways and non-specific defence mechanisms (external surfaces--bound and/or cellular) may suffice under certain circumstances.

Adult↗
PubMedDate not supplied

Autoimmunogenic HLA-DRB1*0301 allele (DR3) may be distinguished at the DRB1 non-coding regions of HLA-B8,DR3,Dw24 and B18,DR3,Dw25 haplotypes.

A novel TaqI restriction fragment length polymorphism (RFLP) of 4.15 kb is reported using a DR beta probe (pRTV1). This fragment corresponds to the DRB1 locus and allows the subdivision at the DNA level of the DRB1*0301 allele (DR3 antigen), which had not previously been reported. Both splits also distinguish each of the two DR3-bearing extended haplotypes (HLA-B8,SCO1,DR3,DQw2,Dw24 and B18,F1C30,DR3,DQw2,Dw25) found associated to several autoimmune diseases as insulin-dependent diabetes mellitus (IDDM), systemic lupus erythematosus (SLE) and myasthenia gravis. The fact that no polymorphism in the DRB1*0301 coding DNA sequence has been detected indicates that DRB1*0301 intronic, regulatory of neighbouring sequences might also contribute to differential disease associations (and pathogenic mechanisms) found linked to each of the two DR3-bearing haplotypes, i.e. IDDM and B8,DR3,Dw24 in North European/American Caucasoids vs IDDM and B18,DR3,Dw25 in Mediterraneans; SLE and B8,DR3,Dw24 in children vs SLE and B18,DR3,Dw25 in Spanish adults.

Autoimmune Diseases↗
PubMedDate not supplied

Exon-2 nucleotide sequences, polymorphism and haplotype distribution of a new HLA-DRB gene: HLA-DRB sigma.

Two new allelic exon-2 HLA-DRB sequences have been identified by using universal and also specific DRB primers. They may correspond to a previously unidentified DRB gene (DRB sigma) and define a new supratypic group ("DRw54") which includes DR1, DR"Br", DR2 and DRw10 bearing HLA haplotypes. This is probably the last HLA-DRB gene to be described in the standard DR haplotypes on the bases of the number of TaqI RFLPs obtained. Sequence comparison with their respective DP and DQ sequences shows that DRB sigma is unequivocally placed within the DRB family and also a constructed "neighbouring homology tree" indicates that DRB sigma gene is probably the eldest in the DRB family, thus the first to diverge from the ancestral DRB gene. An hypothetically deduced DRB sigma beta 1 protein domain was found to be quite different from the corresponding DRB1, DRB3, DRB4 and DRB5 products, since residues 40-55 would bear a longer alpha-helical conformation and would also exist a loss of both the extended conformation at residues 50-54 and the alpha-helix at residues 64-71. Thus, the putative DRB sigma protein would be remarkably different to other DRB ones. Also, a DRB sigma partial transcript (exon-2) has been obtained by PCR of cDNA by using specific DRB sigma oligonucleotides, but a specific Northern blot hybridization has not been achieved.

Alleles↗