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52-P: Anti-GSTT1 antibodies in patients with humoral kidney allograft rejection; its association with C4d deposition on renal biopsies
Abstracts
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52-P
ANTI-GSTT1 ANTIBODIES IN PATIENTS WITH HUMORAL KIDNEY ALLOGRAFT REJECTION; ITS ASSOCIATION WITH C4D DEPOSITION ON RENAL BIOPSIES. Antonia Alvarez-Marquez, Isabel Aguilera, Miguel A. Gentil, Virginia Cabello, Maria F. Gonzalez-Escribano, Antonio Nunez-Roldan. Servicio de Inmunologia, Hospital Universitario Virgen del Rocio, Sevilla, Spain. Presence of circulating donor-specific antibodies (DSA) and the subsequent deposition of complement component C4d on graft endothelium represent the biological evidence of antibody-mediated graft rejection. We have recently demonstrated that liver transplant recipients who are negative (null/null) for the GSTT1 gene and receive a liver graft from a GSST1 positive donor, might produce antibodies against GSTT1 and develop a de novo hepatitis leading to a severe liver dysfunction. To analyse the possible role of GSTT1 in kidney transplantation, 19 patients with acute rejection or with a chronic nephropathy and showing C4d deposition on renal biopsies were studied. Among them, five patients (26.3%) had only anti-HLA class I antibodies; two (10.5 %) had anti-HLA class II abs; three (15.8%), a combination of anti-HLA class I and anti-GSTT1 abs, three patients (15.8%) had only anti-GSTT1 abs and in 6 patients (31.6%), no antibodies were found. Of note, of the 19 C4d positive transplants, only 8 were performed in the context of a GSTT1 mismatch (donorpositive / recipient-negative) and in 6 of them (75%), antibodies against GSTT1 were demonstrated. For comparison, a different group of 22 GSTT1 negative patients, receiving a GSTT1 positive renal allograf without clinical evidence of renal dysfunction, was evaluated; among them, only 6 (27.3%) produce antiGSTT1 antibodies (p ⫽ 0.026, by Fischer’ s exact test). In conclusion, in the case of a GSTT1 donor-recipient mismatch, anti-GSTT1 antibodies are significantly associated with the occurrence of antibody-mediated acute and chronic kidney graft rejection.
53-P
URINARY C4d-CONTAINING COMPLEMENT COMPONENTS CORRELATE WITH GLOMERULAR PROTEINURIA BUT NOT WITH C4d-STAINING OF PERITUBULAR CAPILLARIES. Gideon Hoenger,1 Michael Mayr,1 Michael Dickenmann,1 Michael Mihatsch,2 Stefan Schaub.1 1Clinic for Transplantation Immunology, University Hospital, Basel, Switzerland; 2Institute for Pathology, University Hospital, Basel, Switzerland. Background: C4d-staining of peritubular capillaries (PTC) in allograft biopsies is a hallmark of antibodymediated rejection (AMR). This study investigated whether urinary C4d correlates with C4d-staining of PTC allowing for a non-invasive screening procedure. Methods: Urine samples from 34 patients with diffuse C4d-staining of PTC (C4d-pos group) and 68 urine samples from patients with negative C4d-staining of PTC (C4d-neg group) matched 1:2 according to total proteinuria and time post-transplant were compared regarding urinary C4d-levels. Results: Urinary C4d/creatinine levels were not different between the C4d-pos group (median 0.85g/mmol, range 0-168) and the C4d-neg group (median 2.14g/mmol, range 0-319) (p⫽0.62). Urinary C4d strongly correlated with total proteinuria (r2⫽0.58; p⬍0.0001) and albuminuria (r2⫽0.57; p⬍0.0001) but not with urinary ␣1-microglobulin (r2⫽0.002; p⫽0.70). Twelve of 34 patients (35%) in the C4d-pos group and 24/68 patients (35%) in the C4d-neg group had total protein/creatinine (P/C) levels ⬎50mg/mmol. In both the C4d-pos and the C4d-neg group urinary C4d/creatinine levels were significantly higher in patients with P/C ⬎50mg/mmol than in patients with P/C ⬍50mg/mmol (pⱕ0.005). However, C4d/creatinine levels were not different between C4d-pos and C4d-neg patients with P/C ⬎50mg/mmol (p⫽0.68) and patients with P/C ⬍50mg/mmol (p⫽0.38). Conclusion: Urinary C4d-levels correlate with glomerular proteinuria (i.e. glomerular injury) but not with C4d-staining of PTC. Therefore, urinary C4d is not a useful biomarker for non-invasive screening and monitoring of AMR.
S41
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ANTI-GSTT1 ANTIBODIES IN PATIENTS WITH HUMORAL KIDNEY ALLOGRAFT REJECTION; ITS ASSOCIATION WITH C4D DEPOSITION ON RENAL BIOPSIES. Antonia Alvarez-Marquez, Isabel Aguilera, Miguel A. Gentil, Virginia Cabello, Maria F. Gonzalez-Escribano, Antonio Nunez-Roldan. Servicio de Inmunologia, Hospital Universitario Virgen del Rocio, Sevilla, Spain. Presence of circulating donor-specific antibodies (DSA) and the subsequent deposition of complement component C4d on graft endothelium represent the biological evidence of antibody-mediated graft rejection. We have recently demonstrated that liver transplant recipients who are negative (null/null) for the GSTT1 gene and receive a liver graft from a GSST1 positive donor, might produce antibodies against GSTT1 and develop a de novo hepatitis leading to a severe liver dysfunction. To analyse the possible role of GSTT1 in kidney transplantation, 19 patients with acute rejection or with a chronic nephropathy and showing C4d deposition on renal biopsies were studied. Among them, five patients (26.3%) had only anti-HLA class I antibodies; two (10.5 %) had anti-HLA class II abs; three (15.8%), a combination of anti-HLA class I and anti-GSTT1 abs, three patients (15.8%) had only anti-GSTT1 abs and in 6 patients (31.6%), no antibodies were found. Of note, of the 19 C4d positive transplants, only 8 were performed in the context of a GSTT1 mismatch (donorpositive / recipient-negative) and in 6 of them (75%), antibodies against GSTT1 were demonstrated. For comparison, a different group of 22 GSTT1 negative patients, receiving a GSTT1 positive renal allograf without clinical evidence of renal dysfunction, was evaluated; among them, only 6 (27.3%) produce antiGSTT1 antibodies (p ⫽ 0.026, by Fischer’ s exact test). In conclusion, in the case of a GSTT1 donor-recipient mismatch, anti-GSTT1 antibodies are significantly associated with the occurrence of antibody-mediated acute and chronic kidney graft rejection.
53-P
URINARY C4d-CONTAINING COMPLEMENT COMPONENTS CORRELATE WITH GLOMERULAR PROTEINURIA BUT NOT WITH C4d-STAINING OF PERITUBULAR CAPILLARIES. Gideon Hoenger,1 Michael Mayr,1 Michael Dickenmann,1 Michael Mihatsch,2 Stefan Schaub.1 1Clinic for Transplantation Immunology, University Hospital, Basel, Switzerland; 2Institute for Pathology, University Hospital, Basel, Switzerland. Background: C4d-staining of peritubular capillaries (PTC) in allograft biopsies is a hallmark of antibodymediated rejection (AMR). This study investigated whether urinary C4d correlates with C4d-staining of PTC allowing for a non-invasive screening procedure. Methods: Urine samples from 34 patients with diffuse C4d-staining of PTC (C4d-pos group) and 68 urine samples from patients with negative C4d-staining of PTC (C4d-neg group) matched 1:2 according to total proteinuria and time post-transplant were compared regarding urinary C4d-levels. Results: Urinary C4d/creatinine levels were not different between the C4d-pos group (median 0.85g/mmol, range 0-168) and the C4d-neg group (median 2.14g/mmol, range 0-319) (p⫽0.62). Urinary C4d strongly correlated with total proteinuria (r2⫽0.58; p⬍0.0001) and albuminuria (r2⫽0.57; p⬍0.0001) but not with urinary ␣1-microglobulin (r2⫽0.002; p⫽0.70). Twelve of 34 patients (35%) in the C4d-pos group and 24/68 patients (35%) in the C4d-neg group had total protein/creatinine (P/C) levels ⬎50mg/mmol. In both the C4d-pos and the C4d-neg group urinary C4d/creatinine levels were significantly higher in patients with P/C ⬎50mg/mmol than in patients with P/C ⬍50mg/mmol (pⱕ0.005). However, C4d/creatinine levels were not different between C4d-pos and C4d-neg patients with P/C ⬎50mg/mmol (p⫽0.68) and patients with P/C ⬍50mg/mmol (p⫽0.38). Conclusion: Urinary C4d-levels correlate with glomerular proteinuria (i.e. glomerular injury) but not with C4d-staining of PTC. Therefore, urinary C4d is not a useful biomarker for non-invasive screening and monitoring of AMR.