First results with Capture-P, a solid phase immunoassay for the detection of platelet antibodies.
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Biomedical subjects
Publications and source records attributed to W R Mayr.
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One hundred twenty-seven white European patients with differentiated thyroid cancer were typed for human lymphocyte antigen (HLA) DR specificities. There was no significant deviation from the HLA-DR distribution observed in 160 normal patient controls, neither in the entire group nor in the patient groups with nonmedullary types of thyroid cancer (61 with papillary and 44 with follicular, all nonradiation associated). Also, subdivision of patients with nonmedullary thyroid cancer according to age at diagnosis, presence of metastases, and presence of thyroglobulin antibodies in serum showed no significant deviation from the HLA-DR distribution. For the patients with medullary thyroid cancer (only sporadic [n = 20] or inherited isolated [n = 2] forms, no multiple endocrine neoplasias), there was a significant increase of HLA-DR2 (11 of 22 cases [50%]) in comparison with control patients (22%; P corrected to 0.02; relative risk, 3.6). These data suggest, in contrast to previous reports, that there is no genetic influence on the development of nonmedullary types of differentiated thyroid cancer. Medullary thyroid cancer without multiple endocrine neoplasia, however, may be associated with HLA-DR2.
After a survey of the genetics of the HLA system, the possibility to type bloodstains for HLA gene products is discussed.
Due to the absence of vessels and lymph drainage, human cornea is the tissue grafted with the greatest success. From an immunological point of view, this advantage is lost when the recipient cornea has pronounced vascularization and is sensitized. In such cases, which have a poor prognosis, the postoperative success rate drops to below 50% due to graft rejection. The origin and point of attack of the immune reaction to the graft are the MHC antigens of the donor cornea, which occur on almost all nucleated cells. Since they are capable of triggering a T cell activation in the recipient they set immunological effector mechanisms in motion which lead to elimination of the cells carrying the alloantigen. Corresponding to the MHC antigen expression (both Class I as well as Class II) on all cells in all layers of the cornea, rejection reactions of all the various cell types (epithelial, stromal, endothelial) are also seen. By using histocompatible donor corneas it is possible to influence the afferent arm of the immune response preoperatively and thus to diminish its effect on the postoperative course.
The positive influence of HLA-compatible donor material on successful transplantation was proven especially for prognostically unfavourable cases. Nevertheless it is not clear whether varying importance should be attached to the antigen incompatibilities at the HLA-A and HLA-B locus. 62 keratoplasty patients, 37 of whom had primarily poor prognoses and 25 patients with low risk of transplant rejection were prospectively given transplants in which more than two certain incompatibilities at the HLA-A and HLA-B locus had been ruled out. The number of Ag incompatibilities (separately according to locus) was related retrospectively to postoperative progress. An irreversible transplant failure had occurred in 6 patients (16%) four months after surgery in the high-risk group, whereas 31 transplants (84%) remained clear. The course of healing was without complications within the first four months in all patients with favourable starting position. The influence of the HLA disparities on transplantation success was examined by means of the chi-square test. Taking the Ag incompatibilities of both loci in combination into account showed an only marginally significant (p = 0.1) influence on the survival rate of the transplant. Here HLA-A incompatibilities appear to have only secondary significance, whereas incompatibilities at the HLA-B locus correlated inversely (p = 0.02) with the success of transplantation.
An LD defined split of HLA-DR2, different from HLA-Dw2, Dw12 and DB9, is observed in the Austrian population. The narrow HLA-D specificity, defined by a new Austrian Homozygous Typing Cell (HTC), a primed lymphocyte (PLT) cell line and a PLT clone, is tentatively termed HLA-D"WH". Investigation of three informative families shows that HLA-D"WH" segregated together with HLA-DR2. In one family, even an individual heterozygous for HLA-DR2/Dw2 and HLA-DR2/D"WH" can be identified. A panel study including 90 non-related Austrians shows that HLA-D"WH" occurring in 6.7% of the whole panel, that is in 20% of the HLA-DR2 positive panel members, is completely included in HLA-DR2. HLA-D"WH" might be comparable to other LD specificities related to HLA-DR2, "MN2", "FJO", "AZH" or "GEN".
By isoelectric focusing in a pH range of pH 3.5-9.5 or of pH 5-8, and by using a functional or an immunological detection, a genetic polymorphism of plasminogen can be demonstrated. In Caucasoids, 2 common alleles--PLGA (frequency 0.67) and PLGB (frequency 0.30)--as well as several rare variants (sum of their frequencies 0.03) exist. Systematic studies on the functional activity of the various plasminogen gene products should be performed in order to analyse whether or not a difference of plasminogen activity can be observed amongst the possible phenotypes and in order to see whether or not the various plasminogen phenotypes have any clinical significance.
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In a prospective study to see whether HLA sensitisation is associated with increased red-blood-cell (RBC) destruction after HLA-incompatible transfusion, chromium-51-labelled RBC survival and site of sequestration were monitored in nine patients in whom HLA antibodies had developed after RBC transfusions. The donors selected were compatible in ABO and RBC-specific antigen systems but mismatched for the HLA antigen in question. Haemolytic transfusion reactions occurred in all four patients who received HLA-B7-incompatible RBC. A direct radioimmune anti-IgG test became positive, Cr51-RBC survival was very short (22.3, 36.9, 41.4, and 44.0 days), and excess sequestration in the spleen was measured. There was a rise in serum lactic dehydrogenase and a fall in haptoglobin. HLA-B7 antibody was detected in the eluate prepared from RBC collected after transfusion. A similar reaction was found in only one further patient, caused by an HLA-A2 incompatibility. No indications of immune-mediated RBC sequestration were discernible after transfusion of HLA-B7-compatible RBC in one of the patients who had shown a reaction with HLA-B7-incompatible blood, nor in any of the other patients who received HLA-B7-compatible RBC. The haemolytic transfusion reactions could not be anticipated by conventional crossmatch procedures, nor by the measurement of the Cr51-RBC survival 1 h after transfusion.
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A panel of 120 HLA-A, -B, -C and -DR typed Austrians has been typed for HLA-D by the use of 26 Homozygous Typing Cells (HTC). The new Austrian HTC, partly defined by the 9th International Histocompatibility Workshop (9WS), partly by a checkerboard experiment with internationally well defined reference HTC, type for HLA-Dw1 to -Dw7 and an obviously new, so far unknown HLA-DR2 related HLA-D determinant. Associations of HLA-DR and HLA-D antigens in Austria and their frequencies are determined. Antigen frequencies in Austria are compared to frequencies in other Caucasoid populations.
The possible linkage groups JK-JGK, MNS-GC, GPT-ESD and GPT-HP have been analysed in families of middle-European origin. Linkage of JK-JGK and MNS-GC could be confirmed, the group GPT-ESD needs further data and for GPT-HP no evidence of linkage was revealed.
Immunization of a mother negative for the platelet-specific antigen P1A1 against the P1A1 antigen of her child induced neonatal alloimmune thrombocytopenia. This prompt immune response occurred in her first pregnancy and we were therefore interested to study whether there is an association with genes located within the major histocompatibility complex. We deduced haplotypes of HLA-A, B, C and DR as well as of complement C2, C4 and Bf in the maternal family members.
Intranasal (in) GnRH spray caused induction and maintenance of spermatogenesis and biological paternity in a 28-yr-old man with Kallmann's syndrome. Prior treatment had included GnRH analog administration, which failed to induce puberty, and testosterone (T) enanthate weekly. Prior hCG/human menopausal gonadotropin therapy had resulted in high normal serum T levels and near-normal semen quality, but during subsequent hCG therapy, spermatogenesis markedly decreased. The patient had then received 250 mg T enanthate/month for 2 yr and 7 months; it was discontinued 7 weeks before the in GnRH study began. At its start (July 1984) the subject's testis size was 7 mL, and he had azoospermia, low serum LH and FSH levels, and a serum T of 74 ng/dL (2.6 nmol/L). GnRH was administered in a dose of 200 micrograms (20-120 ng/kg were absorbed into the circulation) every 2 h, seven to nine times a day, between 0700 and 2400 h for 242 days. After 12 days of treatment, serum T had increased to 519 ng/dL (18.0 nmol/L). After 70 days, the patient's sperm count was 11.5 million/mL (4.5 mL ejaculate volume; 70% motility; 36% normal morphology); on day 185, sperm count was 31 million/mL (4 mL ejaculate volume; 54% motility; 36% normal morphology). His spouse conceived on day 162 and delivered a fullterm daughter 265 days later. The probability of paternity was 99.9994%. Our results suggest that induction and maintenance of spermatogenesis as well as fertility in hypothalamic hypogonadism can be achieved with in GnRH therapy if pituitary and testicular function are intact. Spermatogenesis induced by in GnRH has the same quality as spermatogenesis induced by hCG/human menopausal gonadotropin therapy. Patient compliance is probably the most important factor for the success of in GnRH therapy.
In patients with Graves' hyperthyroidism, the relapse rate after antithyroid drug treatment is in the range of about 30-70%. Different attempts have been made to obtain criteria for the prediction of the clinical outcome after drug therapy, especially HLA-DR typing and measurement of TSH receptor antibodies. So far, very conflicting results have been reported. This is not surprising in view of the many genetically controlled and environmental factors that play a role in the pathogenesis of this disease. Moreover, most reports are based on retrospective studies with a relatively small number of patients. Our own data, obtained in a prospective multicenter study, yield strong evidence against the relevance of HLA-DR3 typing (n = 187, sensitivity = 0.38, specificity = 0.67) or measurement of TSH receptor antibodies at the end of therapy (n = 269, sensitivity = 0.49, specificity = 0.72) for the prediction of the clinical course after drug treatment.
Another case of an HLA-B/HLA-C recombination is presented which shows that the locus HLA-C is situated between HLA-A and HLA-B.
We determined in 35 patients with severe thrombocytopenia (AML n = 10; ALL n = 4; CML = 1; idiopathic myelofibrosis n = 1, aplastic anemia n = 1; undergoing bone-marrow transplantation n = 17) factors influencing the corrected count increment (CCI) after platelet transfusions. Out of 195 transfusions 86 (44%) failed to increased platelet counts (CCI less than 5 X 10(9) platelets/l). A significant percentage of transfusion failures occurred in patients with splenomegaly and/or fever (54% vs. 29%; p less than 0.002). Antibodies directed against donor platelets were found only twice. No correlation between reactivities demonstrable by the lymphocytotoxic test (n = 144) or the radioimmune antiglobulin test (n = 67) and the CCI was obvious. HLA antigen identity was also not predictive. Thus, transfusion failures in patients with low alloimmunization will not be predicted by in vitro antibody screenings. The patients' clinical condition has the most important influence on posttransfusion increment.