Search PubMed⌕ Search

Biomedical subjects

G Doxiadis

Publications and source records attributed to G Doxiadis.

16 recordsLinked to original sources
PubMed1998

Complete withdrawal of immunosuppression in kidney allograft recipients: a prospective study in rhesus monkeys.

BACKGROUND: We previously reported the successful withdrawal of immunosuppression in kidney-allografted rhesus monkeys. Recipients had received pretransplant blood transfusions and cyclosporine (CsA) immunosuppression for 6 to 12 months. One animal is still alive at more than 15 years after transplantation. Our hypothesis was that the sharing of a single DR antigen between blood donor and recipient, and the sharing of the same DR antigen with the kidney donor, may be beneficial to allograft survival. We now report on the results from a prospective study. METHODS: The animals received three pretransplant blood transfusions from a single donor sharing one DR antigen with the recipient. Subsequently, a life-supporting kidney from a donor sharing the same DR antigen was transplanted. CsA was given for at least 6 months after transplantation. RESULTS: Two animals rejected their graft at 5-8 weeks after cessation of CsA treatment. One animal is still alive at 700 days after transplantation. This animal showed MLR nonreactivity to its kidney donor, similar to the animal at more than 15 years after transplantation. CONCLUSION: These results demonstrate that withdrawal of immunosuppression may be a realistic option in kidney graft patients under careful immunological monitoring of donor-specific immunity.

Animals↗
PubMed1998

The common marmoset: a new world primate species with limited Mhc class II variability.

The common marmoset (Callithrix jacchus) is a New World primate species that is highly susceptible to fatal infections caused by various strains of bacteria. We present here a first step in the molecular characterization of the common marmoset's Mhc class II genes by nucleotide sequence analysis of the polymorphic exon 2 segments. For this study, genetic material was obtained from animals bred in captivity as well as in the wild. The results demonstrate that the common marmoset has, like other primates, apparently functional Mhc-DR and -DQ regions, but the Mhc-DP region has been inactivated. At the -DR and -DQ loci, only a limited number of lineages were detected. On the basis of the number of alleles found, the -DQA and -B loci appear to be oligomorphic, whereas only a moderate degree of polymorphism was observed for two of three Mhc-DRB loci. The contact residues in the peptide-binding site of the Caja-DRB1*03 lineage members are highly conserved, whereas the -DRB*W16 lineage members show more divergence in that respect. The latter locus encodes five oligomorphic lineages whose members are not observed in any other primate species studied, suggesting rapid evolution, as illustrated by frequent exchange of polymorphic motifs. All common marmosets tested were found to share one monomorphic type of Caja-DRB*W12 allele probably encoded by a separate locus. Common marmosets apparently lack haplotype polymorphism because the number of Caja-DRB loci present per haplotype appears to be constant. Despite this, however, an unexpectedly high number of allelic combinations are observed at the haplotypic level, suggesting that Caja-DRB alleles are exchanged frequently between chromosomes by recombination, promoting an optimal distribution of limited Mhc polymorphisms among individuals of a given population. This peculiar genetic make up, in combination with the limited variability of the major histocompatability complex class II repertoire, may contribute to the common marmoset's susceptibility to particular bacterial infections.

Alleles↗
PubMed1990

Systemic lupus erythematosus in dogs: association to the major histocompatibility complex class I antigen DLA-A7.

The DLA-A,B antigens and the allotypes of the fourth complement component have been determined in German shepherd dogs suffering from systemic lupus erythematosus. We have typed 26 unrelated affected dogs, 11 animals of a three generation family, and 16 dogs of a colony with a high frequency of the disease. The results obtained from the 26 unrelated diseased dogs were compared to those determined in the 23 unaffected German shepherds. The antigen DLA-A7 was found to be predominant in the diseased group with a c2 = 11.02, Pc = 0.02, and a relative risk for the carriers of 11.93. The antigens DLA-A1 and DLA-B5 were negatively associated to the disease (c2 = 14.95, Pc = 0.001, and c2 = 17.16, P = 0.0008 respectively) and thus may be of protective nature. These data were further substantiated by the typing of the three generation family and the colony.

Animals↗
PubMed1990

Antigens of the major histocompatibility complex in patients with chronic discoid lupus erythematosus.

The frequencies of the major histocompatibility complex class I, class II and class III antigens were determined in 130 patients (88 women and 42 men) with chronic discoid lupus erythematosus, and compared with those of 764 healthy controls. A significant increase in HLA-B7 (38.0% in the patients vs. 25.8% in the control group), HLA-B8 (29.5% vs. 17.4%), HLA-Cw7 (58.9% vs. 26.1%), HLA-DR2 (46.9% vs. 29.7%), HLA-DR3 (32.0% vs. 19.4%), HLA-DQw1 (76.6% vs. 60.5%), and a decrease in HLA-A2 (41.9% vs. 55.7%) was found. The calculated relative risk values for the respective antigens markedly increased when two or more antigens were present in one patient, with a maximum relative risk value of 7.4 for the combinations of HLA-Cw7, DR3, DQw1 and HLA-B7, Cw7 and DR3, which were found in 17.2% of the patients and in only 2.3% of the controls.

Chronic Disease↗
PubMed1990

C4 reference typing report.

Human C4 is most polymorphic at the protein level, distinction between allotypes of the C4A and C4B proteins resting on electrophoretic migration patterns and difference in hemolytic activity. The aim of the C4 reference typing has been the definition of reference variants, the assignment of rare variants, and the investigation of duplicated, deleted, or non-expressed and hybrid genes. Samples from 136 individuals, predominantly with known segregation, from 16 laboratories were investigated by standard electrophoretic techniques, for their relative hemolytic activity, reactivity with monoclonal antibodies and Rg/Ch reagents, alpha-, and beta-chain types, relative electrophoretic migration distance, as well as the C4/21-OH-TaqI RFLPs. The results were evaluated in three groups; they consisted in the definition of the eight most common C4 alleles, and the ten Rg/Ch standard phenotypes in group I. In group II twelve C4A and fourteen C4B duplications among 96 complotypes, as well as eighteen deleted/non-expressed C4A and twenty-two C4B alleles, and hybrid alleles were seen by correlation of lytic activity, electrophoretic mobility, and monoclonal and/or Rg/Ch reactivity. Group III consisted of the newly defined allotypes A 8, A 7, A 58, A 55, A 45, B 45, B 35, and B 22, furthermore of alleles subdividing the A 1/A 91, and the B 13/B 12/B 11 regions. The reference typing has allowed reclassification of the majority of described C4 allotypes and resulted in a revision of the C4 nomenclature.

Blood Grouping and Crossmatching↗
PubMed1990

C4 nomenclature statement (1990).

A common and revised nomenclature of the allotypes of the fourth component (C4) of human complement has been proposed. It is based on the results of the C4 Reference Typing of the VIth Complement Genetics Workshop and Conference, Mainz, FRG, 1989, the previous C4 nomenclature and the guidelines for human gene nomenclature (ISGN). The designation of allotypes derives from their relative electrophoretic mobility, the distinction between C4A and C4B proteins from their relative hemolytic activity. Common alleles retain their single digit numeric designation, intermediate variants their two- or three-digit designations; newly discovered alleles should not interfere with already described variants. At least 13 C4A alleles, 16 C4B alleles as well as non-expressed genes at each C4 locus are presently known. There are also duplicated loci of each C4 gene; they should be designated by repetition of the locus symbol at the haplotype or genotype level. As a phenotype they will be placed in parenthesis without repetition of the locus symbol. Aberrant allotypes or hybrid genes should be explained by a special suffix. No special nomenclature is recommended for restriction fragment length polymorphisms. Their designation should follow the general rules of the ISGN.

Alleles↗
PubMed1990

C4 allotyping by prolonged gel electrophoresis and immunoblotting using monoclonal and polyclonal antibodies.

Out of the 136 individual samples mostly from HLA-typed family members which were submitted to the VIth Complement Genetics Workshop 1989, Mainz, FRG, for C4 allotyping, 129 were analyzed by prolonged gel electrophoresis followed by immunoblotting. The blotting was performed using either a Rodger (Rg):1,2 specific monoclonal, 99H7 (provided by G. Mauff, Cologne, FRG), and/or a Chido (Ch):1 specific monoclonal antibody (MoAb), 2B12 (provided by G.J. O'Neill, Miami, USA), and a polyclonal antihuman C4 antibody. In addition, 29 individuals from the workshop panel were tested with a third antibody, 1217, and 20 individuals with a fourth antibody, 1228 (both provided by D. Bitter-Suermann, Hannover, FRG). Due to the improved typing technique a total of 13 C4A and 16 C4B variants could be discriminated, of which some have not yet been described. Considering as a rule that all allotypes with great hemolytic activity are named C4B, the Ch:1 specific antibody 2B12 is reactive with all B allotypes except C4*B11, C4*B12, C4*B13, some C4*B3, C4*B4, one C4*B5, and weakly with one C4*B6 variant. The Rg:1,2 specific antibody 99H7 recognizes all C4A allotypes except for C4*A91, one C4*A1, and some C4*A12 variants. Therefore all these allotypes mentioned may, like C4*A91, express reversed antigenicity. The two additionally tested MoAbs 1217 and 1228 reacted similar to 2B12 with one exception for each. Correlations of HLA haplotypes with C4 allotypes especially with those of reversed antigenicity are discussed.

Antibodies↗
PubMed1989

Relevance of complotyping and subtyping of MHC class I gene products in haplotype definition for allogeneic bone marrow transplantation.

In preparation for a bone marrow transplantation 217 patients and their families were complotyped for Bf, C4A and C4B in addition to the routinely performed HLA-A,B,C,DR and HLA-D typing. In 147 families uncertainties in haplotype definition occurred which could be solved in 37 cases (25%) by complotyping. Additionally, patients and their relatives were subtyped for class I gene products by one-dimensional isoelectric focusing, a method by which serologically identical HLA-A, B, or C antigens could be split in five out of 22 cases tested. The results obtained clearly show the relevance of both methodologies for finding the best match of donor/recipient pairs to help to prevent MHC-induced graft-versus-host disease after bone marrow transplantation.

Bone Marrow Transplantation↗
PubMed1988

Recombination within the class III region by a double cross over event.

Analysis of class I, class II, and class III gene products of the human MHC in a Caucasoid family with four children gave evidence for a double crossing over event in monozygotic twins between the C2, Bf/C4A, C4B gene loci. In view of the small genetic distance between C2 and C4, a point mutation within the Bf locus must be considered alternatively.

Crossing Over, Genetic↗
PubMed1987

HLA-DR4 and Gm 1;21 haplotypes are associated with pseudolupus induced by venopyronum dragées.

The phenotypic frequencies of human major histocompatibility complex class I, II, and III antigens and immunoglobulin allotypes (Gm factors) were determined in 56 patients (55 women, 1 man) who had lupus-like disease induced by venopyronum dragées. The findings in these patients were compared with those of a control group. We found a significant increase of HLA-DR4 (57.1% versus 26.5%, relative risk [RR] 3.7) and a decrease of HLA-DR3 (3.6% versus 19.1%, RR 0.16) in the patient group. In addition, the haplotype Gm 1;21 (60.7% versus 32.9%, RR 3.2), and the phenotype Gm 1,3;5,21 (46.4% versus 25.8%, RR 2.5) were significantly increased. Both the haplotype Gm 1;21 and the phenotype Gm 1,3;5,21 are associated with HLA-DR4 in pseudolupus patients but not in controls. The coincidence of HLA-DR4 and Gm 1;21 markedly increases the risk of acquiring pseudolupus (RR 6.9). We conclude that the pathogenesis of pseudolupus is influenced by at least 2 independent genetic factors. A similar HLA association has been described in hydralazine-induced lupus, and this suggests a common pathogenic mechanism.

Adult↗
PubMed1987

Statement on the nomenclature of dog C4 allotypes.

As a collaborative work of three laboratories the polymorphism of the canine fourth complement component (C4) was studied in a total of 131 unrelated dogs from different breeds and mongrels. Using high voltage electrophoresis followed by an immunoblotting technique, we detected eight distinct variants. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of canine C4 showed an additional heterogeneity of the alpha and gamma chains which resulted in a total of 11 variants in the population studied. So that more precise information concerning the respective C4 allotypes will be available, a nomenclature is proposed designating not only the migration pattern of the C4 variants in agarose gels but also the heterogeneity of the C4 chains observed in SDS-PAGE.

Alleles↗
PubMed1985

Polymorphism of human C2 detected by immunoblotting.

To allotype human complement component C2, thin layer agarose gel isoelectric focusing of human serum and/or EDTA-plasma was performed followed by direct immunofixation or by immunoblotting with a specific anti-human-C2 antibody. Using reference samples for C2 BC phenotypes and local samples from an HLA, C4, and Bf genotyped family, a differentiation of the C2*B and C2*C variants segregating with the respective HLA haplotype was achieved. The C2 BC phenotype is characterized by a double banding pattern similar to that observed in the haemolytic overlay assay usually used for the detection of C2 polymorphism. An homozygous C2*Q0 reference sample determined by functional assays was shown to be biochemically deficient, as demonstrated by immunofixation and immunoblotting. The visual interpretation of C2 phenotypes was definitely easier after immunofixation and immunoblotting than after an haemolytic overlay assay. In addition, the method for C2 allotyping described here has several advantages, in particular it saves time and tolerates repeated thawing and freezing of the samples.

Complement C2↗
PubMed1985

Polymorphism of the fourth complement component in the dog.

The polymorphism of the fourth complement component was studied in 118 unrelated dogs from different breeds and 73 unrelated beagles. In the mixed breed population, five different variants were observed with the following gene frequencies: C4*1 = 3.9%; C4*2 = 13.6%; C4*21 = 6.0%; C4*3 = 9.0% and C4*4 = 51.1%. In beagles, only four variants could be identified with gene frequencies of C4*2 = 24.2%; C4*21 = 1.4%; C4*3 = 20.6% and C4*4 = 46.3%. In both populations analyzed positive linkage disequilibria between certain DLA antigens and C4 variants were recognized. The biochemical analysis of the canine C4 revealed a double-banding pattern for the C4 alpha chain which gives preliminary evidence for two gene loci encoding for the fourth complement component in the dog.

Animals↗