Donor-specific antibodies against HLA, MICA, and GSTT1 in patients with allograft rejection and C4d deposition in renal biopsies.

BACKGROUND: Production of antibodies against donor-specific antigens is one of the central mechanisms of allograft rejection. This antibody-mediated rejection (AMR) is evidenced by the presence of circulating donor-specific antibodies and deposition of complement component C4d on renal endothelium. Although anti-human leukocyte antigen (HLA) antibodies account for a high proportion of AMR, in many cases anti-HLA antibodies cannot be demonstrated. In liver transplant, antibodies against glutathione-S-transferase T1 (GSTT1) expressed on the graft may induce an antibody response leading to a severe graft dysfunction. In addition, presence of antibodies against major-histocompatibility-complex class I chain-related gene A (MICA) has been associated with a poor graft survival in kidney transplantation. METHODS: Pre- and posttransplantation sera from 19 patients fulfilling the criteria for AMR including C4d deposition in renal biopsies were included. Donor-specific antibodies against HLA-I and -II and MICA were studied using Luminex. Anti-GSTT1 antibodies were analyzed by indirect immunofluorescence and by an ELISA method. A control group of 39 patients with graft dysfunction negative for C4d was also included. RESULTS: At the time of the biopsy, 4 (21%) patients had only anti-HLA class I antibodies; 3 (15.8%) had anti-GSTT1, 2 (10.5%) had anti-HLA-class II, and 2 (10.5%) had anti-MICA; four patients had combination of antibodies: HLA-I + MICA (n=1), HLA-I + GSTT1 (n=2), and GSTT1+MICA (n=1). No antibodies were found in 4 (21%) patients. In total, 6 (31.6%) C4d+ patients had anti-GSTT1 antibodies, whereas, among the 39 C4d-negative patients, only 3 (7.7%) had anti-GSTT1 antibodies (P=0.027). CONCLUSION: Besides anti-HLA antibodies, donor-specific antibodies against MICA and GSTT1 antigens could be responsible for the occurrence of antibody-mediated kidney graft rejection.

Anti-glutathione S-transferase T1 antibody-mediated rejection in C4d-positive renal allograft recipients.

BACKGROUND: Chronic humoral rejection is a progressive form of graft injury, with defined diagnostic criteria, the crucial one being the evidence of circulating anti-donor antibodies. These antibodies are mainly directed against human leucocyte antigens (HLA), but other targets have also been described. We previously reported that antibodies against the Glutathione S-transferase T1 (GSTT1) enzyme appear in recipients without the GSTT1 gene who receive a graft from a GSTT1-positive donor. The primary aim of this study was to analyse the role of GSTT1 in cases of antibody-mediated rejection (AMR) in the absence of anti-HLA antibodies. A second objective was to describe the distribution of the GSTT1 enzyme in the human kidney. METHODS: Four renal biopsies from four renal transplanted patients with declined renal function and circulating anti-donor GSTT1 antibodies were studied for C4d deposits in sections of paraffin-embedded tissue samples. Anti-donor-specific HLA and MICA antibody detection was done with the Luminex platform and anti-GSTT1 antibodies were tested by indirect immunofluorescence on rat tissues and ELISA assay. DNA of the patients was extracted for GSTT1 genotyping. RESULTS: Four patients with the GSTT1 donor/recipient mismatch developed anti-GSTT1 antibodies 32, 42, 48 and 60 months after the transplant. One patient also had donor-specific anti-HLA antibodies. Their biopsies showed pathologic lesions compatible with chronic antibody-mediated rejection (CAMR), along with positive C4d deposition in peritubular capillaries in three of them, being no valuable in the other case. CONCLUSION: This is the first study reporting an association between the appearance of chronic antibody-mediated renal allograft rejection and the occurrence of de novo production of anti-GSTT1 antibodies, in the absence of anti-HLA donor-specific antibodies. This fact suggests a potential role of the GSTT1 system in anti-graft immune response.

Síndrome nefrótico en esclerodermia / Nephrotic syndrome in Scleroderma

La afección renal es infrecuente en la esclerosis sistémica, a diferencia de otras colagenosis. La aparición de síndrome nefrótico se ha relacionado con el uso de fármacos, especialmente la D-penicilamina, o raramente como manifestación de amiloidosis secundaria, bastante infrecuente en la esclerosis sistémica. Presentamos un caso de síndrome nefrótico en una paciente con esclerosis sistémica, producido por una glomerulonefritis membranosa, descrito de forma excepcional en la literatura (AU)

The renal affectation is infrequent in scleroderma, unlike other collagen diseases. The appearance of nephrotic syndrome has been related to the drug use, specially the D-penicilamine, or rarely as a manifestation of secondary amilodosis, quite infrequent in scleroderma. We report a case of nephrotic syndrome in a patient with systemic scleroderma, produced by a membranous glomerulonephritis, exceptionally described in literature (AU)

Valor actual de la autopsia clínica en los pacientes con infección por VIH / Current value of clinical autopsy in patients with HIV infection

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Valor de la autopsia clínica en los pacientes receptores de trasplante cardíaco / Value of autopsy in heart transplant recipients

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Valor de la autopsia clínica y causas de muerte en los pacientes receptores de trasplante hepático / Value of clinical autopsy and causes of death in liver transplant recipients

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[Nephrotic syndrome in scleroderma]. / Síndrome nefrótico en esclerodermia.

The renal affectation is infrequent in scleroderma, unlike other collagen diseases. The appearance of nephrotic syndrome has been related to the drug use, specially the D-penicilamine, or rarely as a manifestation of secondary amilodosis, quite infrequent in scleroderma. We report a case of nephrotic syndrome in a patient with systemic scleroderma, produced by a membranous glomerulonephritis, exceptionally described in literature.

Disseminate and fatal cytomegalovirus disease with thymitis in a naive HIV-patient after early initiation of HAART: immune restoration disease?

We describe a naive HIV-infected patient who developed a Pneumocystis carinii pneumonia and disseminate and fatal cytomegalovirus disease within 3 months after initiation of HAART, suggesting due to coincidence in time, an immune restoration disease. We propose an alternative hypothesis.

Masa cervical y extrapleural contralateral de rápido crecimiento en paciente infectado por el VIH / Fast-growing cervical mass and contralateral extrapleural mass in a patient with human immunodeficiency virus infection (HIV)

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Bone involvement and abcess formation by neutrophil-rich CD30+ anaplastic large-cell lymphoma mimicking skeletal infection in an AIDS patient.

Neutrophil-rich CD30+ anaplastic large-cell lymphoma (ALCL) is a rare pathological entity without distinct clinical behavior. Twelve cases of neutrophil-rich CD30+ anaplastic large-cell lymphoma (ALCL) have been reported, three of them were HIV-infected patients. All these reports stressed the presence of neutrophil infiltration as a new morphologic feature of CD30+ ALCL. Only one case of cutaneous involvement presented with microabscess formation. We describe a case of neutrophil-rich CD30+ ALCL in an AIDS patient with a clinical picture determined by the massive neutrophil infiltration of the tumor without necrosis nor local infection, but with the formation of abscesses.