INTRODUCTION AND AIMS: IgA nephropathy (IgAN) recurs in up to 50% of the cases five years after transplantation and recurrence influences the loss of graft function. Genetic and serologic factors have been investigated, but no significant clue to recurrence has been identified. The Italian Ministry of Health sponsored a study group aimed at investigating natural history and factors leading to recurrence of IgAN in grafted kidneys, allowing the analysis of data and biological samples from 361 histologically proven IgAN patients who underwent transplantation.This study aimed to analyzing some immunological aspects possibly involved in IgAN recurrence, focusing on the activation of transcriptional factors NF-kB, AP-1(c-Fos, c-Jun) and Sp-1 in peripheral blood lymphomonocytes (PBMC) of patients with IgAN after kidney transplantation. METHODS: PBMC from transplanted (Tx) IgAN patients were obtained from a) retrospective study: 21 cases (mean 56 y), 7 with histologically proven IgAN recurrence after a median of 84.1mo from Tx; b) perspective study: 17 IgAN cases studied at Tx and 12mo after Tx, none with IgAN recurrence. p50 and p65; cJun and cFos; Sp-1were studied on nuclear and citoplasmic extracts from PBMC in western blot. Bands were detected by ECL system and quantified by Image Master,Total Lab. Data were expressed as relative units. 21 healthy controls (HC) of matching age and sex were studied. RESULTS: In the perspective arm of the study all the transcription factors investigated showed a significant activation on Tx, eventually decreasing after 12mo. In the retrospective arm non-recurrent cases had lower expression of transcription factors with values similar to HC; conversely, in recurrent IgAN transcription factors were more activated and the difference with non recurrent patients was statistically significant for NF-kB. * p=0.0043 IgAN Tx vs Healthy controls p=0.03 IgAN recurrence vs non recurrence. CONCLUSIONS: These data suggest a possible association between activation of NF-kB, AP-1 and Sp-1 and IgAN recurrence after Tx. The ongoing data collection of additional perspective data may help in defining the predictive value of these immunological abnormalities.
Patients with IgA nephropathy present with activated transcription factors after renal transplantation and recurrence of the original disease
SEGOLONI, Giuseppe;Licia Peruzzi;
2009-01-01
Abstract
INTRODUCTION AND AIMS: IgA nephropathy (IgAN) recurs in up to 50% of the cases five years after transplantation and recurrence influences the loss of graft function. Genetic and serologic factors have been investigated, but no significant clue to recurrence has been identified. The Italian Ministry of Health sponsored a study group aimed at investigating natural history and factors leading to recurrence of IgAN in grafted kidneys, allowing the analysis of data and biological samples from 361 histologically proven IgAN patients who underwent transplantation.This study aimed to analyzing some immunological aspects possibly involved in IgAN recurrence, focusing on the activation of transcriptional factors NF-kB, AP-1(c-Fos, c-Jun) and Sp-1 in peripheral blood lymphomonocytes (PBMC) of patients with IgAN after kidney transplantation. METHODS: PBMC from transplanted (Tx) IgAN patients were obtained from a) retrospective study: 21 cases (mean 56 y), 7 with histologically proven IgAN recurrence after a median of 84.1mo from Tx; b) perspective study: 17 IgAN cases studied at Tx and 12mo after Tx, none with IgAN recurrence. p50 and p65; cJun and cFos; Sp-1were studied on nuclear and citoplasmic extracts from PBMC in western blot. Bands were detected by ECL system and quantified by Image Master,Total Lab. Data were expressed as relative units. 21 healthy controls (HC) of matching age and sex were studied. RESULTS: In the perspective arm of the study all the transcription factors investigated showed a significant activation on Tx, eventually decreasing after 12mo. In the retrospective arm non-recurrent cases had lower expression of transcription factors with values similar to HC; conversely, in recurrent IgAN transcription factors were more activated and the difference with non recurrent patients was statistically significant for NF-kB. * p=0.0043 IgAN Tx vs Healthy controls p=0.03 IgAN recurrence vs non recurrence. CONCLUSIONS: These data suggest a possible association between activation of NF-kB, AP-1 and Sp-1 and IgAN recurrence after Tx. The ongoing data collection of additional perspective data may help in defining the predictive value of these immunological abnormalities.
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