A. van Es

Expression of HLA-DR on T lymphocytes following renal transplantation, and association with graft-rejection episodes and cytomegalovirus infection

The expression of HLA-DR by T lymphocyte subpopulations recognized by monoclonal antibodies and flow cytometry was monitored in 10 normal controls, 15 patients on hemodialysis, 25 recipients of a renal allograft with stable graft function, 16 transplant recipients suffering rejection episodes, and 4 transplant recipients with cytomegalovirus (CMV)4 infection. No significant differences in HLA-DR expression were observed in the OKT4-reactive subpopulation among these controls and patients. In the 16 patients who suffered rejection episodes a significant increase in HLA-DR expression by OKT8-reactive cells was observed. In the 10 patients in whom rejection episodes occurred later than 1 week after transplantation, the percentage of OKT8-reactive cells that expressed HLA-DR was dramatically increased 2-6 days before the onset of clinical symptoms of rejection (P less than 0.001 Students t test). When the rejection episode responded to treatment, expression of HLA-DR on the OKT8-reactive cells decreased--whereas in 3 patients who lost their grafts because of irreversible rejection, expression of HLA-DR remained elevated. In addition, the 4 patients with CMV infection had increased percentages of OKT8-reactive cells that expressed HLA-DR (P less than 0.001 Students t test). This increase in expression of HLA-DR coincided with the onset of clinical symptoms of the CMV infection, and the expression of HLA-DR returned to normal values after the titers of antibodies to CMV had increased significantly and symptoms of infection had disappeared.

Effect of warm ischemia time and HLA (A and B) matching on renal cadaveric graft survival and rejection episodes

In a retrospective single-center study the influence of warm ischemia time and simultaneous influence of HLA (A and B) matching on one-year renal graft survival was analyzed in 170 adult recipients of primary cadaveric renal grafts. One-year survival of grafts with warm ischemia times longer than 50 min was only 40% (n = 10). When warm ischemia time was shorter than 50 min, a 1-min increase of warm ischemia time correlated with 1% decrease in one-year graft survival as a result of rejection. This detrimental effect of warm ischemia time on graft survival was not yet significant one month after transplantation, but became more evident as follow-up time was lengthened. Warm ischemia time also correlated with the number of reversible rejection episodes in patients with a graft functioning for longer than one year (P less than 0.04). The beneficial influence of HLA (A and B) matching on one-year graft survival was significant (P less than 0.05 log linear test). This influence was even more evident with longer warm ischemia times. It is concluded that warm ischemia has a detrimental influence on graft survival that is mediated by rejection, and it is suggested that this might be due in part to altered presentation or expression of HLA-antigens of ischemically damaged kidney tissues.

Mononuclear Cells In Renal Allografts: Correlation with Peripheral Blood T Lymphocyte Subpopulations and Graft Prognosis

Cellular infiltrates in 20 renal allograft biopsies taken at the time of acute rejection episodes were analyzed with antibodies reactive with monocytes (BRL antihuman monocyte monoclonal antibody), T lymphocyte subpopulations (OKT- and Leu-series of monoclonal antibodies), and B lymphocytes (heterologous antihuman IgM antibodies). For demonstration of the various mononuclear cells, an indirect immunoperoxidase technique was used. The number of monocytes in the infiltrates varied from 10–20%; the number of B lymphocytes was always below 10%. The T lymphocytes accounted for 50–90% of the total number of mononuclear cells. The OKT4/OKT8 ratios for the T lymphocytes in the graft infiltrates were correlated with the peripheral blood OKT4/OKT8 ratios measured by indirect fluorescence and flow cytometry. The OKT4/OKT8 ratios for perivascular infiltrates correlated far better with peripheral blood OKT4/OKT8 ratios (r=0.72) than did the OKT4/OKT8 ratios for interstitial infiltrates (r=0.58). Low or inverted OKT4/OKT8 ratios and low or inverted Leu 3a/Leu 2a ratios were associated with a high risk of irreversible graft rejection (P<0.001 for perivascular infiltrates).

Renal Artery Stenosis in Kidney Transplantation

Transplant renal artery stenosis (TRAS) of the main renal artery is one of the most frequent vascular complications in clinical renal transplantation. It may be the cause of hypertension as well as interfere with graft function.

Renal graft dysfunction during infection with cytomegalovirus: Association with IgM lymphocytotoxins and HLA-DR3 and DR7

Of 121 consecutive adult recipients of cadaver renal transplants who were treated with low dose steroids and azathioprine, 23 developed active cytomegalovirus infections. These 23 patients were divided into three groups on the basis of their symptoms related to the infection: five patients had no renal, respiratory, or haematological abnormalities; seven had renal dysfunction; and nine had renal dysfunction plus respiratory or haematological abnormalities. Two patients were regarded as a separate group because their infections occurred two to four weeks after graft nephrectomy. All but three of the patients produced IgM or IgG lymphocytotoxins during their infections. In the patients with mild infections and in control patients without infections, however, these lymphocytotoxins were predominantly IgG antibodies that were not precipitated by 3.5% macrogol (polyethylene glycol). In contrast, 12 of the 16 patients with renal dysfunction during their infections had broadly reactive IgM lymphocytotoxins. These IgM lymphocytotoxins lysed T as well as B lymphocytes at 22 degrees C and were precipitated by 3.5% macrogol, suggesting that they were circulating as immune complexes. Rheumatoid factors were found in sera from nine patients with cytomegalovirus infections, seven of whom developed leukopenia or pneumonia, or both, in addition to renal dysfunction. Some of these immune responses associated with cytomegalovirus infection in transplant recipients may be genetically controlled since 10 of 11 patients positive for HLA-DR3 or DR7 produced IgM lymphocytotoxins.

Renal Graft Dysfunction During Infection With Cytomegalovirus: Association With IgM Lymphocytotoxins and HLA-DR3 and DR7

Of 121 consecutive adult recipients of cadaver renal transplants who were treated with low dose steroids and azathioprine, 23 developed active cytomegalovirus infections. These 23 patients were divided into three groups on the basis of their symptoms related to the infection: five patients had no renal, respiratory, or haematological abnormalities; seven had renal dys? function; and nine had renal dysfunction plus respira? tory or haematological abnormalities. Two patients were regarded as a separate group because their in? fections occurred two to four weeks after graft neph rectomy. All but three of the patients produced IgM or IgG lymphocytotoxins during their infections. In the patients with mild infections and in control patients without infections, however, these lymphocytotoxins were pre? dominantly IgG antibodies that were not precipitated by 3-5% macrogol (polyethylene glycol). In contrast, 12 of the 16 patients with renal dysfunction during their infections had broadly reactive IgM lymphocytotoxins. These IgM lymphocytotoxins lysed T as well as B lym? phocytes at 22?C and were precipitated by 3-5% macrogol, suggesting that they were circulating as immune com? plexes. Rheumatoid factors were found in sera from nine patients with cytomegalovirus infections, seven of whom developed leukopenia or pneumonia, or both, in addition to renal dysfunction. Some of these immune responses associated with cytomegalovirus infection in transplant recipients may be genetically controlled since 10 of 11 patients positive for HLA-DR3 or DR7 produced IgM lymphocytotoxins.