No abstract

The anti-tumor response of human invariant NKT (NKT) cells is well established. A novel T cell subset, mucosal-associated invariant T (MAIT) cells, possesses similar regulatory properties to NKT cells in autoimmune models and disease. Here, we examined the clonality of four T cell subsets expressing invariant alphaTCR, including Valpha7.2-Jalpha33 of MAIT cells, in 19 kidney and brain tumors. The MAIT clonotype was identified and co-expressed with NKT clonotype in half of the tumors. In contrast, two other invariant T cell clonotypes (Valpha4 and Valpha19) were not present in tumors. Such tumors also expressed Vbeta2 and Vbeta13, the restricted TCRbeta chain of MAIT cells and the antigen-presenting molecule MR1. A high percentage of infiltrating T cells was CD8+ and expressed HLA-DR suggesting activation. Although the MAIT alphaTCR was identified in both peripheral CD56+ and CD56- subsets, infiltrating lymphocytes were CD56 negative. The clonal presence of MAIT cells in tumors correlated with the expression of pro-inflammatory cytokines but no IL-4, IL-5 and IL-10, suggesting that a pro-inflammatory subset of human MAIT cells may exist. Our data imply that a CD56- subset of MAIT cells may participate in tumor immune responses similarly to NKT cells.

Immunohistochemical analysis of the membrane attack complex (MAC) and the membrane cofactor protein (MCP) was performed on the tubuli and cortical vessels of 46 kidney biopsies with various types of human glomerulopathies. Irrespective of the type of glomerulopathy, significant correlations between tubular MAC and interstitial lymphomonocyte infiltration (p < 0.001) and interstitial volume (p < 0.02) were found. Tubular MCP was significantly overexpressed at the site of MAC deposition (p < 0.002). There was no correlation between the vascular MAC and MCP and tubulointerstitial lesions. Since tubular MAC is deposited in inflamed areas of tubulointerstitium, we propose that MAC might contribute to the development of tubulointerstitial inflammatory processes in human glomerulopathies. MCP as a regulatory factor in the tubulointerstitium might abrogate further tissue damage and cell-stimulatory effects of the MAC.

Genetic variants in CYP2C19 have a gene-dose effect on post-clopidogrel platelet reactivity, with homozygote LOF carriers having the highest risk for HTPR and for adverse ischemic events. Neither ABCB1 nor PON-1 genotypes significantly influenced platelet reactivity or outcome.

The measurement of CD42a- and PAC1-positive microparticles may provide important additional information which can help to improve the early instalment of antifungal therapy of severe septic patients.

Paraneoplastic nephropathy is rarely associated with human tumors. Little is known about the pathogenetic background of this relationship. To our knowledge, no conclusive study of the association of potentially ‘immunogenic’ renal cell carcinoma (RCC) and paraneoplastic nephropathy has been published. For this reason, we performed an immunohistochemical analysis of native resected kidneys of 60 patients with RCC, paying special attention to their pre- and postoperative records. Sixteen (27%) of the 60 tumor patients had immune complex nephropathy (11 IgA nephropathy [IgA NP] and 5 focal segmental glomerulosclerosis [FSGS]). Preoperative proteinuria and/or hematuria observed in 11 of 16 cases disappeared in 6 IgA NP patients within a 2- to 3-month follow-up after nephrectomy. Eleven of 16 tumors stained with the anti human immunoglobulin (IgA or IgM) of the same isotype as that present in glomerular immune complexes. In 3 IgA NP patients RCC-associated von Hippel-Lindau (VHL) protein and IgA staining were found simultaneously in the tumor and glomeruli, with the clinical and laboratory findings disappearing after nephrectomy. Immune injury of the glomeruli due to a tumor-induced antigen-antibody response was demonstrated in these 3 IgA NP patients.

Periodic prospective biopsy evaluation of children who have undergone either colocystoplasty or gastrocystoplasty failed to reveal any histological evidence of malignancy after 10-year followup. However, histological evidence of a premalignant lesion 13 years after followup suggests that screening for premalignant lesions should be initiated no later than 6 to 10 years following enterocystoplasty.

Pituitary adenylate cyclase activating polypeptide (PACAP) occurs and exerts a variety of biological functions in the nervous system and in the peripheral organs, including the urinary system. PACAP has protective effects against myeloma kidney injury and renal ischemia. Ischemia/reperfusion injury of the kidney is a major clinical problem, and based on the protective effects of PACAP in cerebral and cardiomyocyte ischemia, the aim of the present study was to evaluate the effects of a single intravenous PACAP injection on the survival and renal morphology after varying times of ischemia. Rats were subjected to renal artery clamping for 15, 30, 45, 60, or 75 min followed by reperfusion. PACAP (100 microg) was administered intravenously before arterial clamping. We found that a 15- or 30-min renal ischemia led to no renal dysfunction, and the kidneys showed normal appearance with no difference between PACAP- and saline-treated groups. Control rats with 45 min of ischemia had increased premature death rate and showed multifocal acute tubular atrophy, while a 60-min ischemia led to death of all control animals within a few days displaying severe, multifocal Grade II tubular atrophy. In contrast, all PACAP-treated animals survived with subtle morphological changes after the 45-min ischemia. After the 60-min ischemia, death rate was significantly lower in PACAP-treated rats compared to controls, and animals showed subtle focal tubular alteration. A 75-min ischemia was not performable in controls because of deaths before the termination of ischemia. PACAP-treated rats survived longer, but they also died after 5-10 days exhibiting severe focal tubular atrophy. In summary, our results clearly show that PACAP is able to prolong the renal ischemic time, decrease mortality, and attenuate tubular degeneration after renal ischemia.