Regulated necrosis (RN) may result from cyclophilin (Cyp)D-mediated mitochondrial permeability transition (MPT) and receptorinteracting protein kinase (RIPK)1-mediated necroptosis, but it is currently unclear whether there is one common pathway in which CypD and RIPK1 act in or whether separate RN pathways exist. Here, we demonstrate that necroptosis in ischemia-reperfusion injury (IRI) in mice occurs as primary organ damage, independent of the immune system, and that mice deficient for RIPK3, the essential downstream partner of RIPK1 in necroptosis, are protected from IRI. Protection of RIPK3-knockout mice was significantly stronger than of CypD-deficient mice. Mechanistically, in vivo analysis of cisplatin-induced acute kidney injury and hyperacute TNF-shock models in mice suggested the distinctness of CypD-mediated MPT from RIPK1/RIPK3-mediated necroptosis. We, therefore, generated CypD-RIPK3 double-deficient mice that are viable and fertile without an overt phenotype and that survived prolonged IRI, which was lethal to each single knockout. Combined application of the RIPK1 inhibitor necrostatin-1 and the MPT inhibitor sanglifehrin A confirmed the results with mutant mice. The data demonstrate the pathophysiological coexistence and corelevance of two separate pathways of RN in IRI and suggest that combination therapy targeting distinct RN pathways can be beneficial in the treatment of ischemic injury.RIP3 | RIP1 | programmed necrosis | apoptosis

Jin M K, Hoster E, Dreyling M, Unterhalt M, Hiddemann W & Klapper W
(2011) Histopathology 58, 586–592
Follicular dendritic cells in follicular lymphoma and types of non‐Hodgkin lymphoma show reduced expression of CD23, CD35 and CD54 but no association with clinical outcome Aims:  Follicular dendritic cells (FDC) are specialized antigen‐presenting cells found exclusively in the germinal centre (GC), which can be detected in B cell non‐Hodgkin lymphomas (NHL) as reactive bystander cells. Recently, gene expression profiling has revealed that FDC networks might be associated with clinical outcome in follicular lymphoma. The aim was to characterize FDC in NHL and to evaluate a possible association with outcome in follicular lymphoma. Methods and results:  The extent and immunophenotype of FDC was determined semi‐quantitatively in reactive GC and NHL (follicular lymphoma, angioimmunoblastic T cell lymphoma, mantle cell lymphoma) using fluorescence double staining and digital image analysis. In all NHL tested CD23 and CD35 and CD54 were expressed at relatively low levels on FDC, comparable to FDC found in the dark zone of the GC. However, the extent of FDC networks did not correlate with the clinical outcome of 102 patients with follicular lymphomas treated within a prospectively randomized trial. Conclusions:  FDC found in different types of NHL show quantitatively reduced expression of several proteins, suggesting that there are functional differences between FDC in normal GC and NHL. The extent of the FDC networks in follicular lymphoma is not useful as a prognostic marker.

No abstract

We present a case of a false-positive anti-myeloperoxidase (MPO) antibody result on an ELISA in a patient with anti-thyroid microsomal antibody (TMA)-positive hypothyroidism. A 41-year-old woman presented with dyspnea on exertion. The initial evaluation revealed pericardial effusion associated with hypothyroidism. In addition, microscopic hematuria with normal renal function and positive cytoplasmic anti-neutrophil cytoplasmic antibodies (c-ANCA) on immunofluorescent assay were found. In further evaluation, elevated anti-TMA and MPO antibodies by ELISA. While no definite signs of vasculitis were present, the clinical state improved with thyroid hormone replacement and diuretics. Anti-MPO antibody was still positive in the follow-up tests, and microscopic hematuria persisted. On the basis of previous reports that thyroid peroxidase and MPO molecules contain cross-reactive epitopes that are exposed in denaturated molecules, we suggest that in a patient with anti-TMA-positive hypothyroidism, anti-MPO antibody might also be positive on ELISA without clinical signs of vasculitis.