Antibodies to M-type phospholipase A2 receptor (PLA2R) in membranous lupus nephritis.

BACKGROUND: Antibodies to M-type phospholipase A2 receptor (a-PLA2R) have been identified in most patients with idiopathic membranous nephropathy, but the prevalence in membranous lupus nephritis (MLN) is still unclear. The objective of this study was to assess the prevalence of a-PLA2R antibodies in a large cohort of patients with lupus nephritis. METHODS: a-PLA2R antibodies were measured by ELISA in serum from patients with systemic lupus erythematosus ( n = 190), of whom 37 had a biopsy-proven MLN. Positive samples were confirmed by commercial ELISA kit, Western blot and immunohistochemistry in renal tissue. RESULTS: A total of 10 from 190 patients (5.3%) with systemic lupus erythematosus had circulating a-PLA2R measured by in-house ELISA assay. The antibodies were detected in 7 patients with MLN (18.9%) and 3 patients with non-renal lupus disease (3.2%). PLA2R staining was detected in the kidney biopsy of 5 of the 7 (71.4%) patients with MLN. a-PLA2R levels were associated with active disease but not proteinuria levels. Presence of a-PLA2R antibodies at baseline was associated with worse remission rates and longer time to remission compared to those patients serologically negative. CONCLUSIONS: a-PLA2R antibodies can be detected with low prevalence in MLN patients, but their detection is associated with a worse renal prognosis.

Microarray study reveals a transforming growth factor-ß-dependent mechanism of fibrosis in discoid lupus erythematosus.

BACKGROUND: Discoid lupus erythematosus (DLE) is characterized by scarring lesions that develop and perpetuate fibrotic lesions. These are not observed in subacute cutaneous lupus erythematosus (SCLE). The pathophysiological basis of this is currently unknown. OBJECTIVES: To identify contradistinctive signalling pathways and cellular signatures between the two type of lupus, with a focus on the molecular mechanisms leading to fibrosis. METHODS: We conducted a gene expression microarray analysis in lesional and nonlesional skin biopsy specimens of patients with DLE (n = 10) and SCLE (n = 10). Confirmatory reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry were performed on selected transcripts in a new cohort of paraffin-embedded skin biopsies (n = 20). Changes over time of a group of selected inflammatory and fibrotic genes were also evaluated in a second biopsy taken 12 weeks later. In vitro functional studies were performed in primary isolated fibroblasts. RESULTS: Compared with nonlesional skin, DLE samples expressed a distinctive T-cell gene signature. DLE samples displayed a significant CD4 T-cell enrichment with an imbalance towards T helper 1 cytokine predominance and a relative increased forkhead box (FOX)P3 response. RT-qPCR and immunochemical analysis over time showed a progressive increment of fibrotic markers and persistent FOXP3 recruitment. Ex vivo upregulation of SERPINE1, MMP9, TGFBR1, phosphorylated SMAD3 and TGFB1 suggested a transforming growth factor (TGF)-ß-dependent mechanism of fibrosis in DLE, also confirmed by the results observed following in vitro stimulation with TGF-ß. CONCLUSIONS: These results highlight major pathogenic pathways in DLE and provide novel molecular targets for the development of new therapies. The data suggest the existence of a TGF-ß-dependent pathway inducing fibrosis in DLE.

Murine glomerular mesangial cell uptake of apoptotic cells is inefficient and involves serum-mediated but complement-independent mechanisms.

An increased number of apoptotic bodies have been detected in glomeruli of non-nephritic kidneys of C1q-deficient mice. In these mice an in vivo impaired uptake of apoptotic cells by peritoneal macrophages was also demonstrated. Here we investigated whether C1q plays a role in the in vitro clearance of apoptotic cells by glomerular mesangial cells. Phagocytosis was assessed using a novel flow cytometric assay that was validated by immunofluorescence studies. The uptake of apoptotic cells by mesangial cells, measured as percentage of mesangial cells ingesting apoptotic cells, was approximately 25%, 10% and 10% for a T cell lymphoma line (RMA), thymocytes and neutrophils, respectively. The uptake reached a plateau phase after 3 h, was specific for apoptotic cells and was mediated by serum but not by complement components C1q or C3. The phagocytosis of apoptotic cells was significantly inhibited by Arg-Gly-Asp-Ser (RGDS), a peptide capable of blocking the interaction of thrombospondin with CD36 or the vitronectin receptor. Pretreatment of the mesangial cells with dexamethasone (200 nm) but not with LPS increased the uptake markedly. These findings indicate that murine mesangial cells are capable of taking up syngeneic apoptotic cells, although much less efficiently than professional phagocytic cells. They also show that serum proteins other than complement components mediate the removal of apoptotic cells by murine mesangial cells in vitro.

[Effectiveness of (67)Ga scintigraphy in the diagnosis of lymphoma relapse]. / Efectividad de la gammagrafía con 67Ga en el diagnóstico de recidiva de linfomas.

PURPOSE: To establish the clinical effectiveness of 67Ga in lymphoma recurrence. PATIENTS AND METHODS: Thirty-nine patients were assessed on 43 occasions (31 for Hodgkin's disease and 12 for non-Hodgkin's lymphoma) either for a suspected recurrence or to monitor the evolution of the disease. A computed tomography (CT) and a 67Ga whole body scan were performed. Independent observers who did not know the definitive diagnosis performed the CT and 67Ga readings. The gold standard was the biopsy results or the follow-up during a 12 months period. RESULTS: Recurrence was confirmed in 17 cases, while 26 continued to have complete remission. Using 67Ga resulted in true positive (TP), 24 true negative (TN), 2 false positive (FP) and 2 false negative (FN) results with a sensitivity of 0.88 (15/17), specificity of 0.92 (24/26), positive predictive value (PPV) of 0.88 (15/17) and negative predictive value (NPV) of 0.92 (24/26), while CT produced 12 TP, 20 TN, 6 FP and 5 FN, with a sensitivity of 0.7 (12/17), specificity of 0.77 (20/26), PPV of 0.88 (12/18) and NPV of 0.92 (20/25). CONCLUSIONS: 67Ga is a useful indicator and has better diagnostic effectiveness than CT for both the confirmation and exclusion of lymphoma recurrence.

[Diuretic renography in the diagnostic approach of prenatal hydronephrosis]. / El renograma diurético en la estrategia diagnóstica de la hidronefrosis prenatal.

OBJECTIVE: To verify the utility of diuretic renography using 99mTc-MAG3 in the evaluation of the urinary tract obstruction in patients with prenatal diagnosis of hydronephrosis. In a neonate with upper urinary tract dilatation, it is difficult to differentiate a true obstruction from a dilated non-obstructed system. MATERIAL AND METHODS: The retrospective study (january 1993-december 1998) included 40 consecutive patients selected from 181 newborns with a prenatal diagnosis of hydronephrosis. The mean age of the performance of the first renography was 2.6 months. RESULTS: The final diagnosis (once the vesicoureteral reflux was ruled out) was: ureteropelvic junction obstruction (UPJ) 16, megaureter 15, ureterocele 3 and stasis 6. Conservative treatment was applied in most of the patients. Nevertheless, 17 of them needed surgical treatment due to the high risk of the permanent renal damage. CONCLUSIONS: 1) UPJ is the most frequent cause of neonatal hydronephrosis (NH) and consequently, of the request for diuretic renographies. The renography with 99mTc-MAG3 has the greatest influence in the therapeutic decision (identifying who should be operated on and when this should be done), due to the fact that it is the disease with the highest rate of surgical interventions. 2). The surgical indication in NH is based on the diuretic renography parameters and/or on the presence of symptomatology. In our series of surgical patients, none of those who had a differential renal function <20% with regard to the contralateral one showed recuperation after surgery (control 6 months later).