Prognostic Value of the Persistence of C1q-Binding Anti-HLA Antibodies in Acute Antibody-Mediated Rejection in Kidney Transplantation

被引:32
作者
Bailly, Elodie [1 ,2 ]
Anglicheau, Dany [3 ]
Blancho, Gilles [4 ]
Gatault, Philippe [1 ,2 ]
Vuiblet, Vincent [5 ]
Chatelet, Valerie [6 ]
Morelon, Emmanuel [7 ]
Malvezzi, Paolo [8 ]
Parissiadis, Anne [9 ]
Tourret, Jerome [10 ]
Guidicelli, Gwendaline [11 ]
Sayegh, Johnny [12 ]
Mousson, Christiane [13 ]
Grimbert, Philippe [14 ]
Top, Isabelle [15 ]
Le Quintrec, Moglie [16 ]
Purgus, Raj [17 ]
Westeel, Pierre Francois [18 ]
Proust, Barbara [19 ]
Chabot, Valerie [19 ]
Lebranchu, Yvon [1 ,2 ]
Dehaut, Frederic [19 ]
Buchler, Matthias [1 ,2 ]
机构
[1] Univ Hosp Tours, Dept Nephrol & Kidney Transplantat, Tours, France
[2] Francois Rabelais Univ, Tours, France
[3] Hop Necker Enfants Malad, AP HP, Dept Nephrol & Kidney Transplantat, Paris, France
[4] Inst Transplantat Urol Nephrol ITUN, Nantes, France
[5] Univ Hosp Reims, Dept Nephrol & Kidney Transplantat, Reims, France
[6] Univ Hosp Caen, Dept Nephrol & Kidney Transplantat, Caen, France
[7] Univ Hosp Lyon, Dept Nephrol & Kidney Transplantat, Lyon, France
[8] Univ Hosp Grenoble, Dept Nephrol & Kidney Transplantat, Grenoble, France
[9] Etab Francais Sang Alsace, Dept Histocompatibil & Immunogenet, Strasbourg, France
[10] Hop La Pitie Salpetriere, AP HP, Dept Nephrol & Kidney Transplantat, Paris, France
[11] Univ Hosp Bordeaux, Dept Histocompatibil & Immunogenet, Bordeaux, France
[12] Univ Hosp Angers, Dept Nephrol & Kidney Transplantat, Angers, France
[13] Univ Hosp Dijon, Dept Nephrol & Kidney Transplantat, Dijon, France
[14] Mondor Hosp, AP HP, Dept Nephrol & Kidney Transplantat, Paris, France
[15] Univ Hosp Lille, Lab Histocompatibil, Lille, France
[16] Univ Hosp Montpellier, Dept Nephrol & Kidney Transplantat, Montpellier, France
[17] Univ Hosp Marseille, Dept Nephrol & Kidney Transplantat, Marseille, France
[18] Univ Hosp Amiens, Dept Nephrol & Kidney Transplantat, Amiens, France
[19] Etab Francais Sang Ctr Atlantique, Dept Histocompatibil & Immunogenet, Tours, France
关键词
DONOR-SPECIFIC ANTIBODIES; COMPLEMENT-BINDING; ENDOTHELIAL-CELLS; RENAL-TRANSPLANTATION; C1Q ASSAY; RECIPIENTS; ALLOANTIBODIES; SURVIVAL; DETERMINANTS; ACTIVATION;
D O I
10.1097/TP.0000000000002002
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background The differential pathogenicity of anti-HLA donor-specific antibodies (DSAs) is not fully understood. The presence of complement-binding DSAs helps in better defining the prognosis of acute antibody-mediated rejection (ABMR). The evolution of these antibodies after the treatment of ABMR is unknown. Methods We included patients from the French multicenter RITUX ERAH study diagnosed with acute ABMR within the first year of renal transplantation, with circulating anti-HLA DSAs and treated randomly by rituximab or placebo (and intravenous immunoglobulins, plasma exchange). We centrally analyzed serum samples at the time of ABMR, 3 and 6 months after ABMR, with anti-HLA DSAs specificities and C1q-binding capacity assessment. Results Twenty-five patients were included: 68% had C1q-binding DSAs at the time of ABMR. The presence of C1q-binding DSAs was associated with a poorer evolution of chronic glomerulopathy at 6 months (P = 0.036). The persistence of C1q-binding DSAs at 3 and/or 6 months after ABMR was associated with more severe chronic glomerulopathy (P = 0.006), greater C4d score deposition score at 6 months after ABMR (P = 0.008), and graft loss 5 years after ABMR (P = 0.029). C1q-binding capacity was associated with the DSA MFI but 5 C1q-binding DSAs in 4 patients had low MFI values without a prozone effect. Conclusion The presence and persistence of anti-HLA C1q-binding DSAs after ABMR is a detrimental marker, leading to transplant glomerulopathy and graft loss. Assessment of the complement-binding capacities of DSAs could help decide treatment intensification.
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收藏
页码:688 / 698
页数:11
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