Coeliac- and enteropathy-associated autoantibodies in Spanish insulin-dependent diabetes mellitus patients and their relation to HLA antigens.

The frequency of reticulin (ARA), endomysium (EmA), and gut epithelial cell (GECA) autoantibodies, and gliadin antibodies (AGA), was investigated in 86 Spanish diabetic patients by indirect immunofluorescence (IFI) and ELISA, along with their HLA phenotype. Four patients (5%) showed ARA-IgG (R1 pattern), eight (9%) showed AGA-IgG, and eight (9%) showed AGA-IgA. No EmA or GECA-positive patients were found. In diabetic patients, HLA-DR7 is increased in ARA-IgG+ vs. ARA-IgG- (though not significantly), and HLA-DR6 and HLA-DQ1 are significantly increased in the AGA-IgG+ group vs. the AGA-IgG- group. Comparison with a non-diabetic coeliac group showed that HLA-DR4 and HLA-DQ3 are significantly increased in the AGA-IgA+ group, whereas HLA-DQ2 shows a significant decrease in the AGA-IgG+ and AGA-IgA+ patients. Finally, when compared to the healthy group, HLA-DR7 frequency is decreased in the ARA-IgG- group, while HLA-DQ3 is significantly increased and HLA-DR6 and HLA-DQ1 significantly decreased in the AGA-IgG- group.Altogether, these data suggest that the genetic background leading to the appearance of coeliac-specific autoantibodies in Spanish diabetic patients differ depending on the autoantibody produced and is also different to the genetic background leading to diabetes in Spain.

Description of a new kind of MHC DNA sequence in Saguinus oedipus (cotton-top tamarin).

The MHC class I genes of the New World primate the cotton-top tamarin (Saguinus oedipus) are an exception to the high polymorphism and variability usually displayed by this multigene family. In the present work, the cloning and sequencing of a new pseudogene, tentatively named Saoe-Mhc-N4, in this primate species are reported. This new sequence has two characteristic deletions at exon 2, making it very unlikely that any putative protein from this sequence was an antigen-presenting molecule. Comparison of intron 1, intron 2, partial exon 1, exon 2 and partial exon 3 showed little similarity with those of classical class I genes and pseudogenes in S. oedipus and in other primates. Phylogenetic analysis grouped this Saoe-Mhc-N4 sequence with other pseudogenes in S. oedipus. Thus, it seems that Saoe-Mhc-N4 is an inactivated gene or a pseudogene which has been originated by the common process of duplication and subsequent inactivation of MHC class I loci in this primate species.

High polymorphism of Mhc-E locus in non-human primates: alleles with identical exon 2 and 3 are found in two different species.

Thirteen Mhc-E new sequences were found in eight individuals belonging to the Cercopithecinae family, i.e.: Macaca mulatta, Macaca fascicularis and Cercopithecus aethiops when studying E locus polymorphism. No changes were found in the invariant residues which are required for the correct conformation of the peptide presenting region which are conserved in classical Mhc class I molecules from fish and reptiles to humans; however, polymorphism of Mhc-E alleles is not limited to the three typical hypervariable regions per domain as it is in classical class I alleles. The rate of synonymous and nonsynonymous substitutions in the DNA sequence corresponding to the antigen binding site, compared to the remainder of exons 2 and 3 shows that the peptide-binding site is under high evolutionary pressure for stability since only synonymous substitutions have been found to be accepted in apes. Also, a clear example of trans-species evolution of allelism is found: two identical exon 2 and exon 3 sequences there exist belonging to individuals from different species (Mamu-Mhc-E*0101 and Mafa-Mhc-E*04). In addition, two Macaca mulatta individuals show an Mhc-E locus duplication. Finally, phylogenetic tree analysis shows that Mhc class I molecules found in Saguinus oedipus (described as Mhc-G homologues) are closer to Mhc-E sequences.