Biomedical subjects
Publications and source records attributed to G Opelz.
In 20 patients with severe HBsAg negative chronic active hepatitis a significant association has been found between the HLA determinants A1, B8, and Dw3 and cell-mediated immunity directed against human liver specific lipoprotein in vitro. This observation induces further speculation that genetic immunoregulatory action might be involved in the pathogenetic mechanisms of chronic active hepatitis in vivo.
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Among 53 patients with documented Crohn's disease, 30% manifested a defect in delayed hypersensitivity demonstrated by negative DNCB skin tests and significant (p less than 0.01) T-lymphocyte hyporeactivity. A double-blind controlled trial was conducted to evaluate oral Bacillus Calmette-Guerin (BCG) therapy in nine of these patients with Crohn's disease and deficient cellular immunity. All patients had a Crohn's Disease Activity Index (CDAI) greater than 150 (at least moderate activity) upon randomization to BCG (five patients) or placebo (four patients) treatment for six to 12 months. No significicant differences between BCG and placebo treatment were found in the CDAI, laboratory tests and gastrointestinal roentgenograms. We conclude that the disturbance in cell-mediated immunity in patients with Crohn's disease probably is a manifestation of the disease rather than an etiological factor and that immunostimulation with oral BCG is not effective therapy.
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In a study of 1360 cadaver-donor kidney transplants we found a striking correlation of increased numbers of pretransplant blood transfusions with improved transplant survival (P less than 0.0001). Graft survival rate in recipients with greater than 20 transfusions was 71 p5 per cent at one year as compared with 42p2 per cent for recipients with no transfusions; at four years the survival rates were 65p5 per cent and 30p3 per cent (P less than 10(-6). Frozen blood was less effective than nonfrozen blood in producing this effect. In contrast to previous reports based on fewer numbers of transplants, a single pretransplant transfusion of transfusions given during transplantation had no statistically significant influence on graft outcome. The beneficial effect of pretransplant transfusions was apparent at transplant centers with high or low overall success rates. Deliberate transfusion trials in prospective transplant recipients should consider this strong dose dependence of graft prolongation by transfusions.
We examined whether rejection of a previous graft rendered a recipient immunized against subsequent kidney transplants in over 1900 retransplants. The one-year survival rate (43 +/- 1 per cent [ +/- S.E.M.]) of second grafts from cadaver donors was only slightly (but statistically significantly) lower than that of first transplant (47 +/- 1 per cent, P less than 0.02). Repeated HLA mismatches in 180 second transplants did not show a lower survival rate than 925 grafts with no repeated HLA incompatibility. We conclude that the danger of immunization by previous grafts has been overemphasized from studies in laboratory animals. Those who rejected the first graft rapidly (high responders) had significantly shorter survival of the second graft compared with those who rejected the initial graft slowly (low responders) (60 +/- 3 versus 31 +/- 3 per cent at one year, P less than 0.00001).
A correlation was demonstrated between bone-marrow graft rejection and pretransplant lymphocytotoxins. This finding might prove useful as a test for identification of patients at high risk of rejection who might benefit from more intensive immunosuppression.
Thymus cell preparations from four of five myasthenia gravis patients with thymic hyperplasia and from one additional patient with thymic involution stimulated autologous peripheral blood lymphocytes. No autostimulation was observed in two patients with thymoma. Autostimulation as associated with an increase in the fraction of B lymphocytes in the thymus.
Nineteen patients with Sjögren's syndrome were evaluated for the presence of HLA-B8 and HLA-Dw3. HLA-B8 was found in 57.8% of patients and 20.1% of 96 controls (P less than 0.001). HLA-Dw3 was detected in 73.7% of the patients and 24.0% of controls (P less than 0.0001). Statistical evaluation of the association of both antigens with Sjögren's syndrome revealed that the primary association was with HLA-Dw3 (P less than 0.005). Patients with HLA-Dw3 had a lower mean parotid salivary flow rate (0.8 +/- 0.3 ml/10 minutes/gland versus 5.6 +/- 1.2 ml/10 minutes/gland, P less than 0.0004) and a more intense lymphocytic infiltration into labial salivary glands (focus score 7.2 +/- 0.9 versus 3.4 +/- 0.9, P less than 0.04) than did patients without HLA-Dw3. The difference in the intensity of the lymphocytic infiltration was even more significant when patients with both HLA-Dw3 and HLA-B8 were compared with patients with neither antigen (focus score 7.5 +/- 1.0 versus 2.8 +/- 0.8, P less than 0.02). In addition, all patients with severe keratoconjunctivitis sicca had both antigens. Our observations suggest that a number of genes may interact to determine susceptibility and severity in Sjögren's syndrome.
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In 33 renal allograft recipient-donor pairs, B and T lymphocyte complement-dependent cytotoxicity crossmatches and mixed lymphocyte culture (MLC) blocking experiments were performed and the results were correlated with graft outcome. MLC blocking particularly in the unidirectional culture against donor-stimulating cells, was highly correlated with the presence of complement-dependent cytotoxicity antibodies against donor B lymphocytes. Grafts in both MLC blocking and B lymphocyte crossmatch-positive groups fared equally as well as those without positive tests. No difference in graft outcome was noted when the presence or absence of MLC blocking was examined in relationship to positive or negative B lymphocyte complement-dependent cytotoxicity crossmatching.
Statistically significant correlations were found between kidney graft function at 1 day, 1 week, or 1 month and long-term graft survival. Transplant centers with poor early results usually had poor long-term outcome. Assignment of clinical grades to patients with transplants also correlated significantly with subsequent graft survival. It is concluded that monitoring early graft function and clinical grades can be utilized in the assessment of new treatment protocols after relatively short transplant follow-up.
Upon evaluation of 40 subjects with progressive systemic sclerosis (PSS), a significant association of HLA antigens A9 and Aw24 (a subgroup of A9) was found with diffuse scleroderma. HLA-Aw23 (a second subgroup of A9) was also increased in the patients, however, this was not statistically significant. Diffuse scleroderma appears to be one of the few diseases that shows an association with the HLA-A locus.
Bone marrow transplantation from an HLA identical MLC reactive sibling has been performed in a patient with acute myelogenous leukemia resistant to drug treatment. Prompt engraftment was documented; however, the patient died of septicemia 34 days after transplant. Clinical manifestation of graft vs. host reaction was mild but was moderately strong expressed at autopsy tissue samples. Recurrence of persistence of leukemia was found at the time of death.
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B- and T-lymphocyte CDC crossmatches and MLC blocking experiments were performed for 33 cadaver renal allograft donor-recipient pairs. Unidirectional MLC blocking was highly correlated with a positive B-cell crossmatch. Grafts in both the MLC blocking and B-cell crossmatch positive groups fared equally as well as those without positive tests. No difference in graft outcome was noted when the presence or absence of MLC blocking was examined in relationship to B-cell crossmatch results.