Biomedical subjects
Publications and source records attributed to H Festenstein.
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Three cases are described in each of which an HLA identical kidney transplant from a brother was rejected forcefully by the recipient and only one graft survived for more than a year. Rejection of this type is most unusual with well matched grafts and may have been triggered by a system of major antigens that are unassociated with those that are currently recognised.
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The methodology of the conventional mixed lymphocyte culture test has been simplified and miniaturized by developing a micromethod employing Terasaki trays with a final culture volume of 20 mul containing between 10,000 and 20,000 responding and stimulating cells each/culture. This represents one-tenth the cell concentration of the conventional mixed lymphocyte culture. For this new test, a special microharvester has been designed and developed. The test allows accurate and reproducible results giving a high level of discrimination between the different levels of response.
The purpose of this investigation was to see whether or not the hypothetical disease susceptibility locus to ankylosing spondylitis is linked to the MLC determinant 27a. Firstly, we discovered a strong MLC determinant which we called 27a because of its association with the second series specificity W27. Later, we found that this determinant was the same as that which Jorgensen et al. (1973) found to be associated with the second series specificity W5. These MLC determinants may, therefore, be in linkage disequilibrium with more than one HL-A specificity (in this case, of the second series) as previously described by Dupont et al. (1973). However, we found no association between 27a and ankylosing spondylitis. On the other hand, we confirmed the association of ankylosing spondylitis with W27 and also found an increase of HL-A2 of the first series which, however, was not statistically significant. In view of the high incidence of HL-A2 in the general population, more information is required to definitely establish such an association. We found no special association with specificities AJ and Hu (Sa 532), third series antigens, but confirmed their linkage disequilibrium with W27. Disease predisposition loci seem, therefore, to be associated with either type of MHS marker, multiple sclerosis and MLC determinant 7a, or ankylosing spondylitis and the second series antigen W27. It will be interesting to discover whether there is any special significance of the association of one marker rather than another.
In Caucasoids the third locus antigen Hu (FJH or T-2) shows a 91% association with W27 and W10. Less than 10% of the Hu positive cells had an unknown antigen at the second locus. In a Negroid population from Zambia studied with 1972 Workshop data W27 was absent and W10 present in low frequency. Hu in contrast was present with twice the frequency seen in Caucasoids. Eighty-six % of positive cells had an unknown antigen at the second locus. Data from the use of platelet complement fixing sera suggests that this unknown allele was Da(6), an antigen present in very low frequency in Caucasoids. Recombination between second and third locus alleles has been proposed as an explanation for these associations. Associations of HL-A12 and Hu with 4a, W5 with 4b in Caucasoids and vice versa in the Negroids was demonstrated, and the possibility that this finding may be an indication of recombination between a separate 4a/4b locus and the second and third loci was discussed.
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Inhibition of cell-dependent antibody-mediated cytotoxicity has been investigated as a new assay for antibody against cell surface antigens. The cytotoxicity system consisted of effector cells (normal mouse spleen cells), target cells ((61)Cr-labeled chicken erythrocytes), and antitarget cell antibody. Addition of antibody against cell surface antigens in the effector cell population regularly inhibited the cytotoxicity measured in this system. This cytotoxicity inhibition assay (CIA) detected antibody with a variety of specificities: anti-H-2, anti-Thy 1.2, anti-immunoglobulin, and antimouse bone marrow-derived lymphocyte antigen. When the inhibition by anti-H-2 sera was analyzed using effector cells from congenic mice, the activity was found to be directed against specificities mapping in the H-2K, H-2D, and I regions of the H-2 complex, correlating well with the specificities characterized by complement-dependent assays. A comparison between the sensitivity of the CIA and complement-dependent lysis revealed that the CIA was 2-11 times more sensitive for anti-H-2 antisera and 20-780 times more sensitive for certain antisera against subpopulations of the spleen cells (i.e., T cells or B cells). The CIA proved to be precise, sensitive, and reliable. It may become a very useful antibody assay in various species including man.
In a study of 960 pregnancies a significantly higher male to female birth ratio was found among primigravidae who developed HL-A antibodies, which was highest where these were monospecific. In the whole group male births predominated in women with antibodies to HL-A 1 and 11 (first locus) and HL-A 5, 12, and 13 and TYT (second locus).
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