No abstract

The aim of the study was to examine the main intrahepatic lymphocyte subpopulations, namely CD3(+) lymphocytes, natural killer (NK)-like T lymphocytes (NKT) expressing the CD3(+) CD56(+) phenotype, CD56(+) NK cells, CD4(+), and CD8(+) T cells in livers of patients with gastric and colorectal cancer with and without hepatic metastases. The proportion of each lymphocyte subset was determined in 34 patients with gastric or colorectal cancer (18 with and 16 without liver metastasis) by two-color flow cytometry after extraction of hepatic mononuclear cell fraction. The distribution of lymphocyte subpopulations in selected areas of liver metastases and adjacent liver tissue was evaluated using immunohistochemistry for CD4, CD8, and CD56. Flow cytometry analysis revealed a significant decrease in the proportion of CD3(+) CD56(+) cells in metastatic livers, but not in nonmetastatic livers (11.9 +/- 10.3 vs 24.2 +/- 13.6%, p = 0.02). The percentage of intrahepatic CD3(-)CD56(+) cells was also decreased in patients with metastases compared to those without (10.1 +/- 11.6 vs 16.6 +/- 8.9%, p = 0.039). Immunohistochemically, three types of lymphocytes (CD4(+), CD8(+), and CD56(+)) were present in the metastatic tissue, although the number of CD56(+) cells was almost twice lower. We found a low prevalence of tumor-infiltrating CD4(+), CD8(+), and CD56(+) cells in livers with multiple metastases, whereas in cases with solitary metastasis a higher degree of lymphocyte infiltration was observed. The number of CD3(-)CD56(+) and CD3(+) CD56(+) cells was decreased in metastatic livers compared to those unaffected by metastases. Therefore the prevalence of tumor-infiltrating lymphocytes seems to be related to the progression of metastatic liver disease. Depletion of hepatic innate lymphocytes may reveal susceptibility to metastatic liver disease and could be a reason for the escape of metastatic cells from the mechanisms of liver immune control.

In our study, we collected data on 116 patients with biopsy-proven idiopathic or lupus glomerulonephritis who were treated with high doses of intravenous immunoglobulin G (IVIG) (Veinoglobuline or Immunovenin-intact). In all patients a severe nephrotic syndrome (edema, proteinuria >6 g/24 h, serum albumin <22 g/24 h) had been observed. 34 patients had renal failure (serum creatinine up to 504 µmol/l) and 96 hypertension. 98 patients were previously for a long time treated with corticosteroids, immunosuppressors and anticoagulants without any effect. 18 patients had no therapy before IVIG. IVIG had been applied in a dose of 85 mg/kg/24 h 3 times every other day. Depending on the clinical improvement afterwards (in case of therapy resistance or relapse) these boli had been repeated in 84 patients after 1 month (and every 3 months for maintenance of remission) to 7 years. Proteinuria disappeared and full remission occurred in 36 patients. Partial remission was present in 48 patients. 32 patients went into end-stage renal failure and/or died (15 of them of a nonrenal cause). In 13/34 patients with impaired renal function serum creatinine levels go back to normal after treatment. Our results suggested that IVIG therapy may be recommended in patients unresponsive to aggressive conventional treatment.

There is already a considerable amount of evidence suggesting that fibronectin (Fn) plays an important role in the pathogenic process in some forms of glomerulonephritis (GN). It has been postulated that Fn may participate in the progression or regression of glomerular diseases. The Fn is presented in the kidney as a normal component of the mesangium, and it is increased in the expanded mesangium in various forms of GN. This paper reports our efforts to investigate the role of Fn in plasma and kidney in patients with GN. Using monoclonal antibodies against human Fn in the ELISA and immunohistoperoxidase techniques to evaluate Fn, we investigated its quantity in connection with clinical state and morphological findings. We studied 93 patients with GN and 26 renal biopsies. The patients with active forms of mesangial proliferative, membranoproliferative and membranous GN showed increased plasma Fn, and the highest levels were in patients with nephrotic syndrome. Increased tissue Fn correlated with mesangial expansion and with IgG and C3 deposits. We speculate on possible mechanisms of the involvement of Fn in human chronic GN.

Immune responses and their modulation within the liver are critical to the outcome of liver malignancies. In late-stage tumors, secreted TGF-β promotes oncogenic functions and can confer tolerogenicity to some immune cells like DCs. The TGF-β signaling pathway is involved in the control of several biological processes, including immunosurveillance. The aim of the present study was to assess CD1a(+) and CD83(+) DCs and to evaluate the impact of TGF-β pathway on DCs maturation and distribution in the liver metastases from gastric and colorectal tumors. The percentage of CD83(+) DCs in the liver tissue, surrounding metastasis and in the metastasis-free liver was measured by flow cytometry, and TGF-β levels were assessed in the tissue supernatant from the peritumoral liver after mononuclear cell isolation and in the sera of the same patients. CD1a(+) and CD83(+) DCs were observed in the tumor stroma and border. Out of 73 patients, there was cytoplasmic reactivity: of TGF-β1 in 37 (50.7%); of Smad4 in 62 (84.9%); of Smad7 in 46 (63%), and of TGFβRII in 39 (53.4%) of the metastases. The TGF-β1 expression in tumor cell cytoplasm correlated with low CD1a(+) and low CD83(+) DCs infiltration. The tissue levels of TGF-β1, measured by ELISA in the supernatant were significantly increased in metastases than in normal liver. Using a two-color FACS analysis, we found that the percentage of HLA-DR(+) CD83(+) DCs in metastases was significantly decreased as compared with metastasis-free liver tissue. In conclusion, the positive and negative correlations between the mediators from the TGF-β pathway implied the existence of imbalance and suppression of this cytokine activity. The presence of increased TGF-β expression by immunohistochemistry in tumor cells was confirmed by detection of increased TGF-β tissue level in the supernatant from the tissue homogenate. The observation of low numbers of CD1a(+) and CD83(+) DCs in tumor stroma correlated with TGF-β overexpression in tumor cells, a fact that well documents the immunosuppressive role of TGF-β in metastasis development. The increased percentage of CD83(+) DCs in the peritumoral tissue supposes that there could be active recruitment or local differentiation of DCs in the metastasis border, but inside the tumor the immune cells recruitment and activity are suppressed by TGF-β and by other cytokines.