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Abstract. Platelets are thought to play an important role in the initiation and the progression of a variety of glomerulonephritides. This study examined whether platelets induce production of monocyte chemoattractant protein-1 (MCP-1), a chemokine involved in leukocyte recruitment and glomerular injury, by cultured human mesangial cells (MC). To this end, platelets isolated from normal human donors were cocultured with MC at various ratios. MCP-1 synthesis was evaluated by quantitative real-time PCR and enzyme-linked immunosorbent assay. Platelets at 1:100 ratio (MC to platelets) induced an approximately 20-fold increase in mesangial MCP-1 mRNA and protein expression through an obligatory cell-to-cell contact-dependent mechanism. Importantly, blockade of the CD40/CD40 ligand (CD40L) pathway with neutralizing antibodies decreased MCP-1 production by approximately 60%. It was confirmed that CD40 was functionally expressed on MC. Gelshift assays and inhibitors of phosphorylation were used to demonstrate that activation of p38 mitogen-activated protein kinase, protein tyrosine kinases, and nuclear factor-B activation were essential for MCP-1 production. These data indicate that platelet/MC contact stimulates the production of MCP-1 and may contribute to glomerular inflammatory responses by recruiting leukocytes from the peripheral blood.

Antibody (Ab)-mediated pure red cell aplasia (PRCA) is a rare but important side effect in patients with chronic kidney disease who receive recombinant human erythropoietin (rhEPO). Ab-mediated PRCA was first reported in the 1990s, and the incidence subsequently increased and reached a peak in 2001. After improvements in rhEPO products and the administration route, the incidence was reduced by 90%, and now Ab-mediated PRCA only develops in a limited number of patients who receive rhEPO subcutaneously for a long period. We describe here the clinical course of one such rare patient with Ab-mediated PRCA. The patient was a 70-year-old man with chronic renal failure secondary to diabetic nephropathy. He had not received rhEPO therapy before the initiation of hemodialysis. He started hemodialysis and began to receive rhEPO therapy intravenously. Three months later, his hemoglobin level started declining and he became transfusion dependent. A diagnosis of Ab-mediated PRCA was made by bone marrow examination and detection of anti-EPO Abs. He was successfully treated with cyclosporine and became independent of blood transfusions. This case is a reminder that vigilance is required regarding the development of Ab-mediated PRCA upon rhEPO therapy, regardless of the administration route.

Thiopurine methyltransferase (TPMT) catalyses the Smethylation in azathioprine (AZA), thioguanine and 6-mercaptopurine (6-MP).1,2) The low TPMT activity in erythrocytes has been associated with an increased risk of severe and potentially fatal hematopoietic toxicity caused by the accumulation of the cytotoxic metabolites of thiopurine drugs. [3][4][5][6]

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