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I Fehrman

Publications and source records attributed to I Fehrman.

34 records · Page 2Linked to original sources

Increased incidence of sensitization among patients with polycystic kidney disease following pretransplant blood transfusions.

Following pretreatment with at least 5 blood transfusions to 58 nontransfused uremic patients, 23 (40%) formed lymphocytotoxic antibodies against B cells and 9 (15%) against T cells as well. Significantly more (p less than 0.01) patients with polycystic kidney disease (6/16) formed T cell antibodies compared to patients with other diseases. The presence of antibodies delayed kidney transplantation, since significantly more (p less than 0.01) patients without antibodies (28 out of 35) received kidney grafts than patients with antibodies (9 out of 23). 5 patients received kidney grafts despite the occurrence of antibodies against donor B cells, but 3 of the patients lost their grafts within 1 month. In vitro lymphocyte subpopulations were studied in 4 patients before and after each of the planned blood transfusions. No persistent changes in lymphocyte responses to phytohemagglutinin and in mixed lymphocyte culture were seen. T cell subpopulations identified by monoclonal antibodies were unchanged, but the proportion of macrophages/monocytes (OKMl-positive cells) increased from 22 +/- 6 to 46 +/- 10% (p less than 0.05).

Antibodies↗

Blood transfusions as pretreatment for kidney transplantation: immunization rate and effect on cellular immune response in vitro.

A group of 28 untransfused uremic patients was given five or more units of stored blood as pretreatment for kidney transplantation; 9 patients formed lymphocytotoxic antibodies against B cells and 1 patient developed multispecific antibodies against both B and T cell panels (greater than 80% reactivity). During the same period 22 previously transfused patients received up to five transfusions as pretreatment for kidney transplantation. B cell antibodies were formed by 10 patients, and 4 of these patients also formed T cell antibodies, 2 with broad reactivity. Cellular immune reactivity in vitro was studied on frozen cells from 17 randomly chosen patients. After five blood transfusions no significant changes were seen in blood lymphocyte responses to phytohemagglutinin (PHA), Concanavalin A (Con A), or in mixed lymphocyte cultures (MLC) and cell-mediated lympholysis (CML). After transfusion 3 patients got Non-A, non-B hepatitis and were withdrawn for up to six months from the transplantation list because of increased S-ALAT and S-ASAT. Of the 50 patients, 27 have received kidney grafts, 6 out of 20 who were sensitized, and 21 out of 30 who were nonsensitized. Because of positive crossmatches no patient with multispecific T cell antibodies has received a graft. We conclude that our transfusion regimen for kidney recipients has rendered barely one-third of the patients sensitized (mostly against B cells) and 3 out of 50 hypersensitized. No effect on T cell reactivity could be seen following five planned transfusions. Because fewer patients with antibodies received grafts (30% with antibodies, as compared with 70% without [P less than 0.01]) the blood transfusions seem to have led to a selection effect.

Antibodies↗

Pretransplant blood transfusions and related kidney allograft survival.

The impact of pretransplant blood transfusions was analyzed in 130 recipients of related kidney grafts. There was no difference in the graft survival rate between the 85 transfused recipients and the 45 nontransfused recipients, but acute rejection episodes occurred less frequently in the former group, the incidence being 49% versus 69% (P less than 0.05). Multitransfused (greater than 20 transfusions) patients had a significantly better graft survival rate than patients receiving 1 to 20 transfusions and patients receiving no blood, The 3-year survival rates in these groups were 93, 70, and 66%, respectively. Pretransplant dialysis had no effect on transplantation outcome.

Adolescent↗

Lymphocytes from multitransfused uremic patients have poor MLC reactivity.

Lymphocytes from uremic patients showed statistically significantly lower (P less than 0.01) MLC reactivity against pooled stimulator cells as compared with lymphocytes from age matched controls. A consistently low MLC reactivity was recorded in lymphocytes from patients who had received more than 20 units of blood and the lowest responses were seen with cells from patients with multispecific anti-HLA-antibodies. Removal of B cells and removal of phagocytic cells from the responder cells resulted in a significant (P less than 0.05) increase in MLC reactivity in the uremic but not in the control group. Both addition of enriched B cells to autologous enriched T cells and addition of adherent cells to non-adherent autologous cells caused a slight supression of MLC reactivity. PHA reactivity was lower (P less than 0.001) in lymphocytes from the multitransfused patients compared to cells from age matched controls. However, no difference in PHA responses were recorded between lymphocytes from uremic patients who had received less than 20 units of blood and controls.

Blood Transfusion↗

Blood transfusions as "transplantation pretreatment": incidence of immunization against unfractionated lymphocytes, T- and B-lymphocytes.

Since May 1980 patients waiting for cadaveric kidney grafts have been pretreated with at least 5 units of leukocyte poor blood. In this study we have analysed the occurrence of antibodies against unfractionated cells, T and B cells following these transfusions. Of the previously untransfused nineteen patients none formed cytotoxic T cell antibodies while warm B cell antibodies were found in sera from three patients, one being broadly cytotoxic killing also unfractionated lymphocytes. Broadreactive cold B cell antibodies were found in serum from one patient. Of the previously transfused fourteen patients none formed T cell antibodies following transfusions with the "lacking" blood units, while two patients formed warm B cell antibodies. Thus, immunization against B cells was more common than immunization against T cells. The significance of these B cell antibodies is unclear, but these antibodies did not show anti-HLA-DR specificity.

Adult↗

Improved renal graft survival in transfused uremics. A result of a number of interacting factors.

In a series of 229 first-time recipients of cadaveric renal grafts the graft survival was better for the patients that had received 4 or more units of blood, than for those patients that had never received blood; on the other hand, for the patients 1 to 3 units the survival was not better. A relationship between blood transfusion and graft survival was found only for patients receiving kidneys with two or less HLA-A and B incompatibilities. Among the patients receiving 20 or more units of blood, one-half became long-term HBsAg carriers and 60% developed HLA antibodies. A larger proportion of these patients had received grafts with a good HLA-A,B match. The graft survival was better for patients that had been on regular dialysis before the transplantation than those that had not. The choice of dialysis method was also significant, the survival being better for patients that had been on peritoneal dialysis than those on hemodialysis. It would appear that blood transfusion and dialysis treatment had an additive effect on graft survival.

Antibodies↗

In vitro characterization of immunological responsiveness of uremic patients.

Uremic patients are thought to have deficient immune reactivity. The mechanisms for immunosuppression are not known. We have studied various in vitro immune response parameters in lymphocytes from uremic patients and from healthy controls. Using polyclonal activating substances, it was found that PHA and LPS responses were reduced in cells from the patient group compared to the control group (p < 0.05). Furthermore, MLC responsiveness using pooled stimulator cells and polyclonal antibody secretion induced by Staphylococcus aureus bacteria in vitro were reduced in the patients (p < 0.05). No differences with regard to proportions of T/B cells in blood were noted between the two groups. No correlation was found between responses of individual cells to different activating substances, with the exception of PHA and ConA. However, low responses to PHA were usually accompanied by a general low responsiveness. Patients were further subdivided into groups according to the type of dialysis treatment, peritoneal dialysis (PD) or hemodialysis (HD), and to the duration of the hemodialysis period (< and > 1 year). Patients treated with PD showed impaired T cell reactivity with loer PHA responses compared to the HD patients (p < 0.05). Between the HD groups there were no significant differences in mitogen or MLC responses. We believe that the differences between PD and HD were due to the facts that the PD patients were older and not in the same nutritional state as the HD patients.

Adolescent↗

MLC-blocking factors in uremic sera.

In 24 patients on regular hemodialysis, the sera were analyzed for the capacity to inhibit mixed lymphocyte culture (MLC) responsers in lymphocytes from healthy individuals. The sera from 15 of these patients (63%) inhibited MLC>50 per cent compared to control serum. Seven of the MLC blocking sera contained multispecific anti-HLA antibodies. The level of serum urea and serum creatinine was the same in sera with or without MLC inhibition. In two patients with MLC inhibiting sera but with no detectable cytotoxic anti-HLA antibodies, the plasma concentrations of middle molecules were high. The MLC inhibiting effect of anti-HLA antibodies was removed by repeated absorptions with platelets and lymphocytes. However, in sera containing "uremic" factors the MLC inhibiting effect was not removed by absorptions. Ultrafiltrate (cut-off point 50,000 daltons) from uremic plasma also gave inhibition of MLC responses compared to ultrafiltrate from normal plasma. Pooled ultrafiltrate from plasma with high concentrations of middle molecules gave the strongest inhibition. Thus, it is concluded that MLC inhibition in uremic sera is caused by anti-HLA-A, -B, -C, and HLA-DR antibodies and by ultrafiltrate of plasma most probably due to middle molecules.

Antibodies↗

Cadaveric renal graft survival: the bearing of the number of blood transfusions and of dialysis treatment.

In a series of 229 recipients of first-time cadaveric renal grafts the graft survival figures were better the larger the number of blood units transfused prior to transplantation. However, the difference between the groups receiving transfusions and that which did not was statistically significant only for the groups receiving 4 units or more. For the patients receiving more than 20 units there was an elevated incidence of HBs antigenemia and of HLA antibodies. The kidneys received by these patients tended to be better matched than those of the patients given less blood. Graft survival was significantly better for the patients that had been on dialysis than for those that had not. Dialysis was more strongly correlated to graft survival than was blood transfusion.

Blood Transfusion↗