The aim of this study was to compare the clinical characteristics of recurrent and de novo membranous glomerulopathy (MG) among a cohort of 614 recipients transplanted between 1989 and 2006. Lupus nephritides were excluded. The diagnosis was established on protocol biopsies performed 1, 2, 4, or 8 years after transplantation or because of proteinuria/nephrotic syndrome and/or an increased serum creatinine level. HCV infection, cryoglobulinemia, monoclonal gammopathy, skin cancers, Kaposi sarcoma, diabetes mellitus, anti-HLA antibodies, and graft survival were not significantly different between the groups. Seventeen MG were diagnosed in 15 patients (2.45% of the whole group), including 6 recurrent MG (35%) and 11 de novo MG (75%). Recurrent MG occurred earlier than de novo MG (15.58 +/- 19.13 vs 49.27 +/- 32.71 months). Recipients with de novo MG were more frequently infected with HCV, which seemed to be the main etiologic factor for de novo MG, and may be linked to a Th2 polarization of the immune response.

Rheumatoid arthritis-induced AA amyloidosis of the bladder is rare, with fewer than 25 cases reported so far. This localization may be life-threatening with a mortality rate of about 60%, most often due to massive hematuria or multiorgan failure as a result of systemic amyloidosis. We report the case of a 72-year-old woman with a long history of rheumatoid arthritis who developed gross hematuria that induced severe anemia. Ultrasonography and tomodensitometry revealed a large mass localized in the upper part of the bladder. Cystoscopy showed a congestive inflammatory area with a large vesicoperitoneal fistula. Biopsies revealed amyloidosis, and immunohistochemical staining of the specimens defined the process as AA amyloidosis. The amyloid deposits were also found in the rectum, duodenum, uterus and kidneys. This case of rheumatoid arthritis-induced AA amyloidosis of the bladder is characterized by its pseudotumoral aspect and the existence of a vesico-peritoneal fistula: only 2 cases have been reported so far. Treatment was symptomatic, and the patient died from cachexia. The pseudotumoral forms of AA amyloidosis, including amyloidosis of the bladder, deserve an early correct diagnosis. Otherwise, an incorrect diagnosis, especially cancer, may prompt inappropriate treatments.

This retrospective study was conducted to examine whether the presence of Foxp3+ cells in biopsies of kidney transplants displaying early acute rejection (AR) predicted the outcome of the episode. Seventeen biopsies showing AR included in this study were obtained at 42 +/- 30 days after transplantation. Lesions were graded according to the Banff classification. Foxp3 staining was performed on paraffin-embedded sections with a monoclonal antibody after antigen retrieval. We evaluated relationships between the number and the location of Foxp3+ cells, the type of rejection, and the serum creatinine value at 1 year. Foxp3+ cells were detected in 11 of 17 biopsies with AR (9.5 +/- 13.3 cells/mm(2)). These elements were mixed with other interstitial inflammatory cells. Intraepithelial tubular Foxp3+ cells were seen in 9 biopsies (1.5 +/- 2.5 cells/mm(2)). Foxp3+ cells were associated with borderline lesions (25.5 +/- 22.4/mm(2)); type 1 AR (7.18 +/- 9/mm(2)) and type 2 AR (1.99 +/- 3.46/mm(2)). The average number of cells per field was not different in C4d(+) and C4d(-) AR (6 +/- 8.35 vs 8.5 +/- 14.7/mm(2)). Graft loss within the first year was higher among the group of recipients without Foxp3+ cells (3/6) than those with Foxp3+ cells (0/11). All AR with intraepithelial tubular Foxp3 cells had favorable outcomes. Foxp3 has been proposed as a relevant marker of CD4(+)CD25(+) regulatory T cells. This study showed that Foxp3+ cells can be detected in kidney transplant biopsies with AR. The absence of Foxp3+ cells, especially in epithelial tubular cells, might indicate a poor prognosis following an AR episode.

Crescentic IgA nephropathy is an uncommon finding in native kidneys (3%-5%) and in renal transplants. This study was performed to determine the frequency of relapsing crescentic IgA nephropathy after kidney transplantation. Over a 15-year period, 42 patients (25 men, 17 women) of age range 17 to 59 years with biopsy-proven IgA nephropathy in their native kidneys were entered into this retrospective study, because they had undergone kidney transplantation and had sequential allograft biopsies during their follow-up. Mean follow-up after transplantation was 8.9 years (range, 1-15 years). In their native kidneys, 5 patients (12%) had more than 20% crescents, and only 2 (5%) had more than 50% of glomeruli involved. As expected, 52.4% of recipients showed recurrent mesangial IgA deposits in their kidney grafts. The 2 patients with diffuse crescentic IgA nephropathy in their native kidneys experienced acute graft dysfunction at 15 and 47 months. Graft biopsy showed recurrent IgA deposits with cellular crescents in 30% and 20% of glomeruli, respectively. Despite corticosteroid pulse therapy, graft failures occurred 2 and 27 months later. No crescentic proliferation was observed during follow-up in any other case. Only 5 other grafts failed because of chronic allograft nephropathy, without any relationship to the relapse of IgA deposits. These data suggested for the first time that only diffuse crescentic IgA nephropathy in the native kidneys was associated with the occurrence of crescents in the kidney transplants, a finding that raises the possibility of a particular subgroup of IgA nephropathies.

Hereditary systemic amyloidosis comprises several autosomal dominant diseases caused by mutations in a number of plasma proteins, including the fibrinogen Aalpha-chain. Four mutations in the fibrinogen Aalpha-chain that are able to induce amyloidosis have been identified so far, the most common being the Glu526Val mutation. We have observed a family in which the father and his son reached end-stage renal failure because of renal amyloidosis induced by a frame-shift mutation in the fibrinogen Aalpha-chain gene producing a novel amyloid protein. Two kidney transplantations in the father and one in the son resulted in fast graft loss caused by recurrence of amyloid deposition. We then performed hepatorenal transplantation in the son. Three years later, liver and kidney functions are normal without recurrence of amyloid deposition. This case, together with three others with the Glu526Val mutation in the extensive literature, suggests that liver transplantation can cure hereditary fibrinogen amyloidosis, whatever the mutation may be.

The aim of this study was to determine the expression of transforming growth factor-beta (TGFbeta)-1 and type I TGFbeta-receptor on sequential biopsies from renal transplants with and without chronic allograft nephropathy. Twenty-four renal transplant recipients entered the study. They underwent sequential biopsies performed before (T1: 1.44 +/- 1.2 months) and 6 months after (T2: 15.96 +/- 7.2 months) transplantation. Lesions were graded according to the criteria of the Banff classification. C4d was detected by fluorescence microscopy. Immunohistochemistry was performed in order to identify cells expressing TGFbeta-1 and type I TGFbeta-receptor. In normal renal tissue (n = 4), TGFbeta-1 is expressed by tubular epithelial cells and endothelial cells lining glomerular and peritubular capillaries, whereas type 1 TGFbeta-receptor is expressed by tubular epithelial cells and smooth muscle cells in the media of arteries. In recipients with chronic allograft nephropathy (group 1, n = 14), diffuse epithelial expression of both molecules was found in more patients at T2 than at T1 (42.8% vs 21.4%). In contrast, this pattern of expression remained stable or decreased over time in recipients with long-term normal transplants (group 2, n = 10). Furthermore, type 1 TGFbeta-receptor was detected on the smooth muscle cells of arteries in 12/14 (85.7%) of recipients in group 1 and only in 4/9 (44.4%) of recipients in group 2. No relationship was noticed with regard to C4d deposits. These data suggest that the synthesis of TGFbeta-1 and type I TGFbeta-receptor increases over time in recipients developing chronic allograft nephropathy. Further studies are in progress in order to quantify mRNA of both molecules with real-time polymerase chain reaction.

The aim of this study was to assess the feasibility of detecting anti-HLA antibodies in eluates from needle core biopsies of renal transplants with chronic allograft nephropathy. Two methods of screening, the enzyme-linked immunosorbent assay (ELISA) and flow cytometry (FlowPRA) were compared. Twenty renal transplants with CAN were removed after irreversible graft failure. To assess the feasibility of detecting anti-HLA antibodies in small samples, needle core biopsies were sampled at the same place as surgical samples and at a second cortical area. Antibodies were eluted with an acid elution kit and anti-class I and class II IgG HLA antibodies detected using ELISA and flow cytometry. Flow cytometry was found to be more sensitive than ELISA for detecting anti-HLA antibodies in eluates from renal transplants with CAN (95% vs. 75% of positive cases). Detection of anti-HLA antibodies showed good agreement between surgical samples and needle core biopsies performed at the same place for anti-class I (80% vs. 65%, r=0.724 P<0.01) and anti-class II HLA antibodies (70% vs. 55%, r=0.827 P<0.01). In addition, differences in the detection of anti-class I HLA antibodies in needle core biopsies sampled at different sites suggests that immunization to class I donor antigen could be underestimated in needle core biopsy samples. These data indicate that anti-HLA antibodies can be detected in needle core biopsies from renal transplants. Provided further evaluation is done, elution might be a complementary method to detect anti-HLA antibodies when they are bound to the transplant.

Donor-specific antibodies may play an important role in the development of chronic allograft rejection process. However, the mechanisms leading to intimal vascular proliferation and fibrosis remain poorly understood. The aim of this study was to examine whether donor-specific HLA antibodies induce overexpression of tissue factor (TF) by endothelial cells. HLA typed human umbilical vein endothelial cells (HUVEC) were incubated for 1 to 12 hours with LPS (10 μg/mL), and increasing concentrations (1 to 500 μg/mL) of anti-HLA A1 antibody specific for an antigen expressed by HUVEC and of an anti-HLA A2 antibody for which A2 was not expressed by the HUVEC. Expression of TF mRNA transcripts was quantified using real time Q-RT PCR and TF activity was tested in cell lysates of cultured HUVEC using a chromogenic TF activity assay. HUVEC-specific anti-HLA A1 antibody at low concentrations (10 μg/mL) induced both a significant increase of TF mRNA transcripts after 1 hour of incubation and TF activity after 3 hours incubation compared to incubation with medium alone or with the nonspecific anti-HLA A2 antibody (n = 4 for all experiments, P < .05). These data show for the first time that specific anti-HLA antibody can induce overexpression of TF on endothelial cells. TF, a transmembrane glycoprotein involved not only in the onset of the coagulation cascade, but also in cell proliferation and anti-apoptotic processes, may play a role in the development of alloantibody-induced chronic rejection.

L'association d'un syndrome de Sweet et de la maladie de Crohn est rare. Nous en rapportons une nouvelle observation. Une femme de 45 ans a été hospitalisée devant une éruption cutanée fébrile brutale, évocatrice d'un syndrome de Sweet, et accompagnée d'une diarrhée. Le diagnostic de maladie de Crohn a alors été porté. La corticothérapie générale, associée à la mésalazine, s'est révélée efficace à la fois sur l'atteinte cutanée et digestive. Les dix cas rapportés dans la littérature et le nôtre montrent que le syndrome de Sweet peut survenir au cours d'une poussée de la maladie de Crohn. Celle-ci est le plus souvent connue mais ce n'était pas le cas chez notre malade, ce qui fait l'originalité de notre observation. La corticothérapie générale représente le traitement de choix.The association of Sweet's syndrome and Crohn 's disease is rare. We report a new case of a such association. A 5 year-old woman developed a diarrhea, fever, and skin lesions consistent with a presumptive diagnosis of Sweet's syndrome. Crohn 's disease was also diagnosed. Oral prednisone, associated with mesalazine, effected improvement of both cutaneous lesions and bowel disease. The ten cases of the literature and ours show that Sweet's syndrome may occur during an acute phase of Crohn's disease. Most of the time, Crohn's disease has already been diagnosed. However, this was not so with our patient, wherein lies the originality of our case. A general corticotherapy is the prefered course of treatment.

P273 Aims: In order to look at a possible relationship between humoral mechanisms of rejection and chronic allograft nephropathy (CAN), the percentage of plasma cells, the presence of C4d deposits in kidney allograft biopsies, and of donor-specific HLA antibodies (DSA), either in biopsy eluates or in sera were studied sequentially and correlated in allograft recipients with CAN. Methods: Kidney allograft biopsies and patients serum samples were taken either systematically during the follow-up, or on the occasion of chronic dysfunction of the graft, before the sixth month (T1), within 8-24 months (T2), and more than three years after grafting (T3) from 10 recipients with CAN observed at T3 (Group 1=G1) according to the Banff criteria, and from 8 recipients with normal and stable renal function and minimal changes on renal allograft biopsy at T3 (Control group=G2). Diffuse C4d deposits in peritubular capillary walls were detected with an indirect immunofluorescence technique. The percentage of plasma cells on transplant biopsies was calculated by two independent experts. Class I and class II DSA were detected by flow cytometry (FlowPRA) in serum samples and in transplant biopsy samples according to a previously described method, using beads coated with specific class I or class II HLA antigens (One Lambda, Canoga Park, CA). Results: Histopathological lesions of CAN developed progressively over time: 10% at T1, 30% at T2, and 100% at T3. The mean percentage of plasma cells in biopsy samples was respectively 12.3% (G1) vs 0.4% (G2) at T1 (p = 0.06), 8.2% vs 0.7% at T2 (p=0.07), and 6.4% vs 0.2% at T3 (p=0.07). C4d deposits were only observed in group G1 and increased over time: 25% at T1, 50% at T2 and 57% at T3 (p<0.05 at T3 vs G2). Class I and/or class II DSA were identified in serum samples (11% at T1, 64% at T2 and 18 % at T3) and/or in biopsy eluates of Group 1 (10% at T1 and 40% at T3). Taking DSA positivity in serum and/or biopsy eluate samples together, DSA were found in 72% of patients with CAN. DSA were eluted from only one early biopsy of a recipient in Group 2 with reversible acute rejection, and were found neither in serum samples nor in late biopsies. The difference between the two groups is statistically significant at T2 and T3 (p<0.05). In Group 1, a significant association was found between a plasma cell infiltrate of more than 5% at T1 and C4d deposits at T3 (p=0.0012), as well as between C4d deposits and the appearance of DSA at any time during the follow-up (p=0.024). Conclusions: These data seem to confirm that humoral mechanisms play a major role in inducing CAN. Indeed, as in previous studies, we found more than 70% of DSA in CAN, and the appearance of such DSA correlates with the presence of diffuse C4d deposits and with more than 5% of intra-graft plasma cells soon after grafting. In addition, each of these three parameters independently correlates with CAN. Interestingly, the frequency of C4d deposits progressively increased over time, thus suggesting that such humoral mechanisms could act progressively by inducing progressive lesions of the graft. It is also of interest to notice that the presence of more than 5% of plasma cells in early biopsies could be of value in predicting chronic allograft nephropathy.

La néphropathie chronique de l'allogreffe (NCA) qui se traduit cliniquement par un dysfonctionnement chronique du transplant rénal, reste la principale cause de perte tardive du transplant rénal. Ses mécanismes sont multiples et encore mal compris. Le but de ce travail est d'étudier l'expression du TGFβ1 et de son récepteur de type 1 en fonction de la pathologie initiale et de rechercher un lien avec la NCA. Trente quatre transplantés rénaux ont été inclus dans cette étude. Les biopsies du transplant rénal, réalisées lors de dysfonctionnement ou à titre systématique ont été classées, selon le délai écoulé après la transplantation, en biopsie précoces (délai 6 mois). Les lésions du transplant ont été évaluées selon la classification de Banff 1997. L'expression du TGFβ1 et son récepteur de type 1 ont été déterminés par immunohistochimie et les dépôts de C4d ont été recherchés sur coupes congelées par une technique d'immunofluorescence indirecte. Une technique sensible de cytométrie en flux (FlowPRA) a permis de détecter les anticorps anti-HLA dans les sérums prélevés au moment des biopsies. Les pathologies observées sur les biopsies précoces ont été classées en 4 groupes : rejet aigu humoral (n = 11), rejet aigu cellulaire (n = 7), toxicité médicamenteuse (n = 6) et lésions non spécifiques (n = 10). Des lésions de NCA ont été observées sur les biopsies intermédiaires de 14 patients alors qu'un dysfonctionnement chronique du transplant est apparu chez 17 receveurs. Le profil d'expression du TGFβ1 et de son récepteur n'était pas statistiquement différent dans chaque groupe lésionnel et au cours de la NCA. Néanmoins, nous avons observé au cours du développement de la NCA, une augmentation des types cellulaires exprimant cette cytokine et son récepteur suggérant que leur synthèse est augmentée au cours de cette pathologie. À l'inverse, les RA cellulaires, associés dans cette étude à une durée d'ischémie froide réduite (p = 0,03) et à une faible incidence de dysfonctionnement chronique, ont été suivi par une diminution de l'expression du TGFβ1 par les cellules épithéliales tubulaires et du récepteur de type 1 par les cellules musculaires lisses des parois artérielles. Dans cette étude, le RA humoral, la toxicité médicamenteuse et les lésions de conservation reste les principaux facteurs de risque de la NCA. Une augmentation, au cours du temps, des types cellulaires marqués par le TGFβ1 et son récepteur de type 1 a été observée durant l'apparition NCA sans qu'il soit toutefois possible d'établir un profil d'expression à risque de cette cytokine en fonction de la pathologie initiale.

Background. Chronic allograft nephropathy (CAN), which remains the main cause of graft loss after kidney transplantation, is still poorly understood. Because anti-HLA antibodies may be involved in the pathogenesis of CAN, this study was performed to look for donor-specific antibodies (DSA) fixed onto renal transplants with CAN. Methods. DSA were identified after elution with flow cytometric assay and/or flow cytometric crossmatches in 20 transplants removed after irreversible graft failure caused by CAN and in control samples from 2 transplants with relapsing glomerulopathy, 2 transplants lost after vascular thrombosis, and 4 normal kidneys. The results were compared with those obtained in the serum samples 1 year after grafting, at the time of transplantectomy, and within 2 months after transplantectomy. Results. IgG anti-class I, anti-class II, or both DSA were identified in 70.6% of eluates versus 73.6% of posttransplantectomy serum samples (NS), 42.1% of 1-year postgrafting serum samples (P <0.05), and 31.6% of serum samples at the time of transplantectomy (P <0.05). Our data show a good correlation between the target of anti-HLA antibodies found in both eluates and posttransplantectomy serum samples, but the precise specificity of anti-HLA antibodies is more often assigned in posttransplantectomy serum samples than in eluates. This problem needs further evaluation. Conclusion. This study shows that testing for anti-HLA DSA in eluates from removed kidney transplants using flow cytometry can be achieved and is highly efficient. It already suggests that both anti-class I and anti-class II HLA antibodies can be involved in CAN. Further studies are now needed to evaluate the possibility of identifying such antibodies in the eluates of transplant biopsy specimens from recipients experiencing CAN.

A 55‐year‐old man was placed on haemodialysis at the age of 46 years because of progressive renal insufficiency secondary to chronic glomerulonephritis. At the age of 47 years, he received a cadaver renal transplant. He was also treated with methylprednisolone, azathioprine and ciclosporin. The patient had type III skin. He was an indoor worker with occasionial weekend sun exposure. Five years later he developed multiple, small, asymptomatic discrete pits and keratotic plugs on the palms. (Fig. 1). No other dermatologic abnormalities were observed. A punch biopsy specimen revealed hyperkeratosis and a cornoid lamella. (Fig. 2). The features were those of punctate porokeratosis. Porokeratosis encompasses a group of uncommon inherited or acquired disorders of epidermal keratinization characterized by typical clinical features associated with a distinct histopathological pattern whose halllmark is the cornoid lamella.1 Several clinical forms of porokeratosis are recognized: linear porokeratosis, disseminated superficial actinic porokeratosis, disseminated superficial form, porokeratosis palmaris plantaris et disseminata and punctate porokeratosis. The aetiology and pathogenesis of porokeratosis are unknown but are certainly multifactorial. The lesions are thought to arise from the peripheral expansion of an abnormal mutant clone of epidermal keratinocytes located at the base of the parakeratotic column.1 The following factors have been considered to play a role in the genesis of lesions: genetic susceptibility, ultraviolet exposure,2 infectious agents and systemic immunosuppression.3–5 A pathogenic relationship between latent viral infection (papillomavirus) and porokeratotic lesions has been hypothesized but never documented. Such an explanation could account for why porokeratosis is confined to the palms. Immunosuppression may exacerbate or initiate the development of porokeratosis in predisposed patients, perhaps through impairment in the immune surveillance function of Langerhans' cells or it may directly trigger the development and proliferation of a mutant clone of keratinocytes.

Over the last 20 years, our understanding of cutaneous adverse drug reactions has improved, especially with regard to the management of affected patients. The pathophysiological mechanisms have been studied to improve our understanding. We report different clinical and histological features of cutaneous drug reactions to distinguish a non drug-induced rash from a cutaneous adverse drug reaction.

A case of a chondroblastoma of the skull-base associated with a persistent hypoglossal artery (PHA) is presented. Neuroradiological findings of the PHA and the tumour are reported. The existence of a carotico-basilar communication such as a PHA should be recognized prior to skull base surgery because of the potential risk of cerebral ischemia.