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Background. Urinary mononuclear cells (UMCs) were studied in IgA nephropathy (IgAN) in relation to clinical and histopathological parameters. Methods. A two-color flow-cytometry analysis was used to phenotype and quantitate UMCs in patients with IgAN (n = 37) and those with other kidney diseases (n = 27). Results. The IgAN patients had higher numbers of UMCs than the patients with other kidney diseases. Macrophages (CD14+; P < 0.0001) and T lymphocytes (CD3+; P = 0.0001; CD4+, P < 0.0001) were predominantly found. In the IgAN patients, the quantities of urinary CD3+, CD14+ cells correlated with impaired renal function; namely, serum creatinine, creatinine clearance, and urinary protein excretion. The UMCs were associated with histopathological changes such as glomerular segmental lesions (r = 0.511; P < 0.01 for CD3+; r = 0.623, P < 0.0001 for CD4+, and r = 0.552; P < 0.001 for CD14+) and the index of glomerular hypercellularity (r = 0.405; P = 0.01 for CD3+ T cells and r = 0.392, P = 0.01 for CD14+ macrophages). Moreover, the UMCs reflected the severity of pathology, as estimated by the glomerular score (r = 0.424; P < 0.01 for CD3+; r = 0.458; P < 0.01 for CD4+; r = 0.500, P = 0.001 for CD14+ cells). UMCs were weakly correlated with tubulointerstitial changes. Conclusion. UMCs were associated with the clinical stage of IgAN and mirrored the extent of histopathology in the kidney. Flow-cytometry analysis of UMCs may help to predict the course of the disease.

The effects of recombinant human erythropoietin (rHuEpo) treatment and blood transfusions on the composition of lymphocyte populations in chronic renal failure patients undergoing maintenance hemodialysis treatment were examined. Immune cells were investigated in the peripheral blood of 122 hemodialysis patients using two-color flow cytometry analysis. For detection of lymphocyte surface markers, a panel of monoclonal antibodies reactive with the following molecules was used: CD3, CD4, CD8, B cell, CD16, CD56, T-cell receptor αβ heterodimer (TCR αβ), T-cell receptor γδ heterodimer (TCR γδ), and human leukocyte antigen (HLA)-DR. Hemodialysis patients who received rHuEpo treatment were found to have significantly lower percentages of CD3 + lymphocytes compared with untreated patients. rHuEpo administration was shown to affect mainly the subset of T cells bearing TCR αβ (TCR αβ + ). A relative increase in the activated TCR αβ + subsets and a decrease in the nonactivated TCR αβ + subsets were observed in rHuEpo-treated individuals. The significantly elevated TCR αβ + and TCR γδ + subset activation indexes found in patients who received rHuEpo suggested a state of activation of the immune system. A history of blood transfusions was shown to be associated with a higher proportion of cytotoxic (CD8 + ) T cells and a decrease in the helper-suppressor index. Blood transfusions had an effect on the T-cell receptor-bearing lymphocyte populations similar to that of rHuEpo administration. We conclude that both rHuEpo treatment and blood transfusions contribute to altered cellular immunity in end-stage renal disease.

Immunogenetic studies have suggested the role of the T-cell receptor (TCR) in the development of immune-mediated diseases. We investigated whether a genetic polymorphism in the TCR constant alpha (Calpha) chain region might modify the susceptibility or progression of immunoglobulin A (IgA) nephropathy. The TCR Calpha chain genotype was studied in 213 Japanese patients with IgA nephropathy and 73 individuals from the general population. A polymerase chain reaction-based TaqI restriction fragment length polymorphism assay (TaqI RFLP) was applied on the 5' flanking region of the TCR Calpha first exon. The TaqI-undigested (t) and TaqI-digested (T) alleles showed similar genotype distributions between the patients with IgA nephropathy and controls (tt:Tt:TT = 16.9%:46.5%:36.6% in IgA nephropathy v 9.6%:58.9%:31.5% in controls; chi(2) = 1.9; P = not significant). To further investigate the role of TCR Calpha chain gene polymorphism in renal prognosis, we analyzed those patients with IgA nephropathy in whom renal status had been monitored for a period of more than 3 years (n = 182). According to outcome, two groups were formed. The stable (S) group included 98 patients with renal function that remained unchanged during an average follow-up of 10.7 +/- 0.4 (SE) years. The progressive (P) group (n = 84) included patients with progressively declining renal function, with an average follow-up of 11.9 +/- 0.5 years. The genotype distributions of the TCR Calpha chain gene polymorphisms between these two groups differed significantly (tt:Tt:TT = 25.5%:40.8%:33.7% in S v 10.7%:44.1%:45.2% in P; chi(2) = 7.0; P < 0.05). The frequency of the T allele was greater in the P group (67.3% in P v 54.1% in S; chi(2) = 6.6; P = 0.01). The TT or Tt genotypes were more commonly observed in patients from the P group (89.3% of T allele carriers in P v 74.5% in S; chi(2) = 6.5; P = 0.01). It appeared the T allele might foreshadow a poor renal prognosis, conferring a potential risk for developing renal failure with time (odds ratio, 2.7; confidence interval, 1.2 to 6.0; P < 0.05). In summary, TCR Calpha chain genetic variability was associated with loss of renal function over time in patients with IgA nephropathy. In conclusion, the TCR Calpha chain polymorphism might prove helpful to predict progression to chronic renal failure in Japanese patients with IgA nephropathy.

Immune cell subsets, when measured by two-color flow cytometry in a population of 129 hemodialysis patients, showed significant variance from normal values. Lymphopenia, decreased absolute counts, and altered percentage values of immune cells were found. Increased proportions of CD3+, T cell receptor (TCR) alpha beta + cells and CD4+ T lymphocytes were present. An abnormally high percentage of a subset of activated TCR alpha beta + cells (alpha beta + DR+) was also seen in hemodialysis patients. The proportion of B lymphocytes was found to be significantly lower as compared with controls. Relative values for TCR gamma delta+cells, both for activated (gamma delta + DR+) and nonactivated (gamma delta + DR-) subsets, as well as for CD8+ lymphocytes and natural killer cells did not vary from those of normal controls. Also, the CD4+/CD8+ ratio showed no significant change. Analysis of absolute counts of the investigated immune cell populations revealed significantly decreased numbers for the majority of subsets, as a result of the preexisting lymphocytopenia, characteristic of end-stage renal disease. We conclude that profound quantitative alterations of immune cells, including TCR+T cells subsets, exist in hemodialysis patients. These account, at least in part, for the immune dysregulation associated with chronic renal failure.