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Biomedical subjects

V Lenhard

Publications and source records attributed to V Lenhard.

At least 37 records · Page 2Linked to original sources

Influence of Lewis and other blood group systems in kidney transplantation.

In 167 first cadaver kidney recipients and their donors the blood groups ABO, Rhesus, Lewis, MN, Ss, P, Kell and Duffy were determined. The influence of incompatibility in each system as well as of simultaneous presence of several mismatches was analysed. Whereas one-year graft survival of Lewis-compatible grafts was 67 per cent (p = 0.02). The other blood groups showed no significant effect on graft outcome. Cumulative red cell incompatibilities, however, led to decreased survival rates. One-year graft survival in the group with greater than or equal to 4 incompatibilities was only 51 per cent versus 69 per cent in transplants with less than 4 incompatibilities (18% difference, p less than 0.01). When the Lewis system was excluded from analysis, the difference in survival rates was reduced to only six per cent. These data indicate that cumulative incompatibilities of red cell antigens have an unfavourable effect on graft survival. Of the different blood groups, the Lewis system is of major importance.

Blood Group Antigens↗

Clinical and serological features of mesangial IgA glomerulonephritis.

IgA-glomerulonephritis (IgA-GN) accounts for approximately 20 per cent of all glomerulonephritis in our unit. Seventeen out of 50 patients with IgA-GN developed renal failure, which appeared in 11 out of 17 over the course of a mean follow-up of 68 months. Haemodialysis was required in three patients. Twenty-two out of 50 patients had hypertension, five with malignant hypertension. Perivascular IgA deposits were found in skin biopsies of 29 per cent of patients with IgA-GN and also in 19 per cent of patients with other GN, but not in healthy controls. Mucosal (salivary and nasal) secretory IgA concentrations were normal. In cutaneous and glomerular IgA/IgM deposits, IgA1 was demonstrated using monoclonal antibodies. No excess of HLA-A, B or DR antigens and no relation of clinical course and HLA-Bw35 were found.

Adolescent↗

HLA phenotypes and idiopathic nephrotic syndrome in children.

Ninety-four children with idiopathic nephrotic syndrome (17 steroid-resistant with a histological diagnosis of a focal segmental glomerulosclerosis) were typed for HLA-A, B and DR antigens. The patients showed a significant increase of DR7 (58% vs 18%, p less than 0.0001) and of B8-DR3 (27% vs 5%, p less than 0.05). Combination of both markers (DR7 and B8-DR3) was observed in 14 per cent of patients but in none of the controls (relative risk 15.2). Patients with B8-DR3 and DR7 had a more severe course of INS.

Child↗

A "spontaneous" cold-reactive IgM antibody with anti HLA-B8 specificity in a patient with multiple sclerosis.

A case of a 35-year-old female with multiple sclerosis is reported who developed without apparent prior sensitization a lymphocytotoxic antibody with anti-HLA-B8 specificity. The antibody persisted for several years with the same titer. The cytotoxic activity of the patient's serum was contained within the IgM fraction. The antibody reacted optimally at low temperature, exclusively against lymphocytes homozygous for HLA-B8. In B8-heterozygous cells, cytotoxic reactions were obtained only following enzymatic pretreatment. The antibody's binding avidity was weak; for its complete absorption, many times more B8-positive lymphocytes or platelets were needed than for a "normal" anti-B8 antibody of the same titer. In HLA redistribution and blocking experiments, it was demonstrated that the antigenic determinant recognized by this antibody is carried by the B8 molecule. It is unclear whether "spontaneously" occurring cold-reactive IgM antibodies with HLA specificity are induced by viral agents or whether they reflect "spontaneous" clonal lymphocyte proliferation.

Absorption↗

[Current immunologic aspects of kidney transplantation].

The results of clinical kidney transplantation are mainly dependent on immunologic factors many of which are unknown or of unspecified importance. Blood transfusions have a favorable effect on graft prognosis, although our knowledge about optimal transfusion protocols and transfusion-induced mechanisms is still incomplete. The value of HLA-typing is controversial: whereas compatibility of the "classical" HLA-A,B,C antigens improves graft survival only moderately, HLA-DR typing, routinely performed for the last 3 years only, might be of greater importance. In addition, non-HLA systems, such as endothelial/monocytic antigens or the Lewis blood group system, appear to play a role in graft rejection. The individual immune reactivity a recipient to a large extent determines the fate of a graft. The multifactorial dependence of graft prognosis is discussed in this report.

Blood Group Incompatibility↗

[Occurrence of HLA-antigens in patients with hypertrophic cardiomyopathy].

The etiology of hypertrophic cardiomyopathy with (HOCM) and without obstruction (HCM) is poorly understood. Controversial data have been published concerning the association of HLA-B-12-antigen with HOCM and HCM respectively. Further, HLA-D-antigen occurrence has been determined in few patients with HOCM or HCM. In 29 patients with HOCM, 38 patients with HCM, and matched healthy persons we determined the occurrence of HLA-A, B, C and DRW-antigen using the test of microcytotoxicity in lymphocytes. HLA-antigens occurred with similar frequency in patients with HOCM and HCM and in control subjects. 25% of the patients and 23% of the control subjects had HLA-B-12. Further, no difference was detected in the frequency of occurrence of HLA-antigens in patients with HOCM and in patients with HCM. The data support the view that HLA tissue typing is of no diagnostic value in identifying patients with HOCM or HCM.

Adult↗

Effects of crude and purified human chorionic gonadotropin on lymphocyte response.

Human chorionic gonadotropin (hCG) preparations with different biological activities were tested for their inhibitory effects on mitogenic of allogenic induced lymphocyte response. Various crude hormone batches inhibited the lymphocyte reaction in a dose-dependent manner. However, we found a varying suppression of lymphocyte response not correlated to the biological activity (2,660-4,300 IU/mg) of crude hormone. Fractions with very low gonadotropic activity (much less than 500 IU/mg) showed a 100-fold inhibition of lymphocyte reaction. Conversely, the enrichment of highly purified hCG with strong biological activity (greater than 10,000 IU/mg) had no inhibitory effect on mitogenic or allogenic induced lymphocyte transformation. Isoelectrofocussing and immunoelectrophoretic investigations indicated that the inhibition is probably caused by nondialyzable sialoglycoproteins. It is therefore very doubtful whether hCG plays an important part in maternal tolerance of the fetal allograft.

Chorionic Gonadotropin↗

MLR inhibitory activity of pretransplant anti-donor B cell antibodies, and kidney graft survival.

The prognostic significance of different types of pretransplant anti-donor B cell antibodies on graft outcome was studied in 193 cadaver kidney recipients. Additionally, in 84 combinations the MLR inhibitory activity of patient sera was determined, and the relationship of pretransplant anti-donor B cell antibodies, MLR inhibitory activity in graft outcome was analysed. Graft survival was high in recipients with cold B cell antibodies, whereas it was unfavourable in recipients positive for warm B cell antibodies. MLR inhibitory activity was highly correlated with the latter type of antibody. In patients with high pretransplant MLR inhibitory activity graft outcome was significantly impaired. In recipients wild cold-reactive B cell antibodies who had excellent graft outcome, MLR inhibitory activity was not demonstrable.

Antibodies↗

Body iron stores in children with chronic renal failure in relation to HLA phenotypes.

In 57 children with chronic renal failure (19 on conservative treatment, 25 haemodialysis and 13 after transplantation) body iron stores were determined by an immunoradiometric assay with a heterologous antibody system in relation to haemochromatosis alleles, HLA A3 and B7. Iron overload, predominantly found during haemodialysis, depended on the number of erythrocyte transfusions given and was found to be more pronounced in patients with HLA A3 and/or B7. The frequency of these antigens was significantly higher in patients with iron overload (91%) than with normal (43%) or decreased (44%) iron stores. The relative risk of iron overload was calculated to be 2.0 for HLA A3 and 8.7 for HLA B7. The results suggest that erythrocyte transfusion therapy should be minimised in children with haemochromatosis alleles in order to avoid organ damage by haemosiderosis.

Child↗

[Increased success rate of renal transplantation by HLA-DR-typing: a retrospective analysis of the South-German co-operative study group for renal transplantation (author's transl)].

Retrospective HLA-DR-typing and the influence of HLA-DR antigen on transplantation prognosis was studied in 90 kidney donor-recipient pairs. It was clearly demonstrated that HLA-DR compatible donor kidney provides a significantly better transplant prognosis than if there is HLA-DR incompatibility. Donor kidneys with only one identical HLA-DR antigen gave a six-month survival rate of 80%. Only HLA-AB identical cadaver kidneys ("full house identity") give similar survival times. Because of relatively lower polymorphism of the HLA-DR alloantigen system, HLA-DR identical donor organs are discovered more frequently than when HLA-AB antigens are taken into consideration. HLA-DR identical donor kidneys (identical for both HLA-DR antigens) have an even better transplant prognosis than "full house identical" kidneys, since the survival rate in the former is 87% after six months.

HLA Antigens↗

Blood transfusion-induced suppression of cellular immunity in man.

The effect of planned blood transfusions on cell-mediated immunity was studied in previously nontransfused prospective kidney graft recipients. Following transfusion of washed erythrocytes a marked suppression of cellular immunity was found, indicated by reduced response to mitogenic (PHA, Con A, PWM) and antigenic stimulation (Ag-C containing PPD, tetanus toxoid, streptolysin, mumps, vaccinia antigen). A second transfusion led to a more pronounced and prolonged immunosuppression. No suppression was found when autologous blood was applied to volunteers. Preliminary results show autologous and allogeneic MLR suppression when mitomycin-C treated patient cells taken after transfusion are added. Our findings indicate that blood transfusion-induced suppression of cell-mediated immunity might be caused by an unspecific suppressor cell.

Blood Transfusion↗

A new human monoclonal cold agglutinin Sa recognizing terminal N-acetylneuraminyl groups on the cell surface.

A human homogeneous IgM/K cold agglutinin (CA) Sa is described, whose corresponding antigen on erythrocytes (RBC) was abolished by neuraminidase. This indicated that the antigen was related to N-acetylneuraminic acid, similar to Pr and Gd antigens. In contrast, this antigen was only partially destroyed by proteases, whereas Pr antigens are completely destroyed and Gd antigens are not influenced by proteases. Sa antibody activity was inhibited by sialyllactose NeuAc (alpha 2 leads to 3) (alpha 2 leads to 6) Gal (beta, 1 leads to 4) Glc like anti-Gd but in contrast to anti-Pr. The corresponding antigen was associated with an RBC membrane glycoprotein fraction like Pr, Sa is one of a spectrum of human monoclonal CA against cell surface neuraminyl groups.

Aged↗

Results of kidney transplantation in relation to HLA-A, B, DR matching and quality of donor organ.

The influence of HLA compatibility as well as immediate postoperative function on survival rates was investigated in 203 cadaver kidney transplants. HLA compatibility, especially DR compatibility, improved transplant survival significantly. A direct correlation was found between primary transplant function and long-term results. HLA compatibility and quality of the donor organ had a cumulative effect on kidney transplant survival. Our results are a further indication that besides HLA compatibility, optimal quality of donor organs has crucial significance for the results of transplantation.

Follow-Up Studies↗

Prognostic significance of B and T cell antibodies in kidney transplantation.

The prognostic significance of pre- and post-transplant B and T cell antibodies was studied in 183 cadaver kidney transplantations. Our results confirm previous reports that a successful kidney transplantation can be carried out in spite of a positive crossmatch due to B cell antibodies. However, it is doubtful whether such antibodies have a protective effect. The success rate seemed to be higher only in patients with preformed cold antibodies. The occurrence and persistence of allogeneic anti-donor antibodies directed against T cells was significantly associated with an unfavourable graft prognosis. Patients with post-transplant anti-donor B cell antibodies had lower (but not significantly) graft survival rates. These findings provide additional evidence for a crucial role of anti-donor antibodies in kidney graft outcome.

Antibodies↗

HLA antigens in children with idiopathic nephrotic syndrome.

HLA antigens were examined in 146 children with idiopathic nephrotic syndrome (INS). These comprised 107 steroid-responsive cases, histologically characterised by minimal change glomerular lesions (MC), and 39 steroid-resistant patients with focal-segmental glomerulosclerosis (FSGS). In the MC groups, B8 was significantly increased as compared to controls (30% vs 18%, p less than 0.01), and this applied in particular to children with atopic features (38% B8 positive). In contrast to other reports, the frequency of B12 in steroid-responsive INS was not different from that of the control group. In FSGS, however, B12 was remarkably increased, especially in patients with a persistent or progressive nephrotic syndrome (45% vs 22%, p less than 0.025). These findings indicate that immunogenetic factors play a major role in INS, and that MC and FSGS are two different disease entities.

Child↗