Loss of a renal graft due to recurrence of anti-GBM disease despite rituximab therapy.

The recurrence of anti-glomerular basement membrane (anti-GBM) glomerulonephritis (GN) in renal transplants is very rare. We report on a patient that developed acute renal allograft dysfunction due to anti-GBM GN relapse 18 months after transplantation. As plasmaseperation, dose escalation of MMF, steroids and cyclophosphamids did not result in an improvement of the graft function, a therapy with the anti-CD20 antibody Rituximab was established in addition to plasmaseperation, cyclophosphamid and steroids. Although this resulted in a decrease of anti-GBM antibody titer, graft function deteriorated further and a renal replacement therapy had to be initiated.

A case report of the efficient reduction of calcium channel antibodies by tryptophan ligand immunoadsorption in a patient with Lambert-Eaton syndrome.

Lambert-Eaton myasthenic syndrome (LEMS) is a neuromuscular transmission disease caused by autoantibodies directed against voltage-gated calcium channels (VGCC). We report on a patient with LEMS and a cerebellar syndrome associated with lymphatic proliferation in the thymus. As thymectomy and immunosuppressive therapy failed to efficiently reduce clinical symptoms and VGCC antibody titer, we performed immunoadsorption using a tryptophan-ligand column for the first time. Repeated treatments resulted in a considerable decrease in antibody levels and a marked subjective and objective amelioration of LEMS as well as of the cerebellar symptoms.

Expression of the chemokine receptor CCR1 in human renal allografts.

BACKGROUND: Chemokines are involved in the recruitment of leukocytes to vascularized allografts. CCR1 is a receptor for various proinflammatory chemokines and CCR1 blockade reduces renal allograft injury in rabbits. The purpose of the study was to characterize CCR1-positive cells in human renal allografts. METHODS: Formalin-fixed, paraffin-embedded allograft nephrectomies (n = 9) and non-involved parts of tumour nephrectomies (n = 10) were studied. Immunohistochemistry for CCR1, CD3 and CD68 was performed on consecutive sections. Double immunofluorescence for CCR1 and CD3, CD20, CD68, DC-SIGN and S100 was used on selected cases. Expression of CCR1 mRNA and the ligands CCL3 and CCL5 was studied in renal allograft biopsies with acute rejection (n = 10), with chronic allograft nephropathy (n = 8) and controls (n = 8). RESULTS: CCR1 protein was expressed by circulating cells in glomerular and peritubular capillaries, colocalizing with CD68. In renal allografts CCR1-positive cells were present within glomerular tufts, but only scattered CCR1-positive cells were found in tubulointerstitial infiltrates. CCR1 did not colocalize with the majority of CD68-positive cells in the interstitium. The small number of CCR1-positive interstitial cells were identified as CD20- or DC-SIGN-positive by double immunofluorescence. CCR1 mRNA was significantly increased in renal biopsies with acute allograft rejection (P < 0.001), and with chronic allograft nephropathy (P < 0.05), it correlated with the expression of CCL3 and CCL5, and with serum-creatinine. CONCLUSIONS: CCR1 mRNA expression was associated with renal function in allografts. CCR1 protein expression was restricted to monocytes, CD20-positive B cells and DC-SIGN-positive dendritic cells. Thus most interstitial macrophages were CCR1 negative, which may relate to down-regulation after migration into the interstitium in human renal allografts.

The contribution of B cells to renal interstitial inflammation.

Local B-cell infiltrates play a role in tissue fibrosis, neolymphangiogenesis, and renal allograft survival. We sought to characterize the B-cell infiltrates, factors involved in B-cell recruitment, and lymphangiogenesis in renal interstitial injury (ie, acute and chronic interstitial nephritis and chronic IgA nephropathy). CD20-positive B cells formed a prominent part of the interstitial infiltrating cells. Together with CD3-positive T cells, the CD20-positive B cells formed larger nodular structures. CD10-positive pre-B cells were rare, and the majority were mature CD27-positive B cells. Proliferating B cells were detected within nodular infiltrates. The level of mRNA expression of the chemokine CXCL13 was increased and correlated with CD20 mRNA in the tubulointerstitial space. CXCL13 protein was predominantly found at sites of nodular infiltrates, in association with CXCR5-positive B cells. Furthermore, sites of chronic interstitial inflammation were associated with a high number of lymphatic vessels. B-cell infiltrates form a prominent part of the interstitial infiltrates both in primary interstitial lesions and in IgA nephropathy. CXCR5-positive B cells might be recruited via the chemokine CXCL13 and seem to contribute to the formation of intrarenal lymphoid follicle-like structures. These might represent an intrarenal immune system.