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Objective To analyze the donor specific antibody (DSA) in liver transplantation,and discuss the therapeutic schemes.Methods We retrospectively analyzed prospectively collected samples from 139 cases of liver transplantation from September 1,2013 to July 1,2015.Luminex assays were applied to determine human leukocyte antigen,panel reactive antibody (PRA).For PRA positive cases,DSA,C1q and C4d were detected,and liver biopsy was done.Results Of 139 cases enrolled,there were 12 cases positive for DSAs,including 2 cases of PreDSA:1 case of Ⅰ DSA (HLA-A mismatch),and 1 case of Ⅱ DSA (HLA-DQ mismatch).Ten cases of de novo DSA (including 1 case of PreDSA) all were HLA-DQ mismatch.The liver biopsy on 5 cases showed hepatic fibrosis,early rejection and intrahepatic cholestasis,and only 2 cases showed positive C4d.Of 6 cases of DSA,5 cases showed positive C1q.In the patients positive for DSA,tacrolimus dose was adjusted postoperatively,adding mycophenolatemofetil or increasing its dose,or methylprednisolone and immunoglobulin given.Conclusion DSAs are important indicators of sensitized recipients in liver transplantation,associated with trends toward worse outcomes in patients or allografts.The monitoring of DSA is requisite in order to adjust the immunosuppressant.
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Objective To investigate the significance of glomerular deposition of C4d in accessing the severity and prognosis of IgA nephropathy. Methods A total of 131 patients were recruited for the study. Immunofluorescence was used to detect the deposition of C4d in renal tissue of pa?tients with IgA nephropathy,and the relationship between C4d deposition and clinical and pathological parameters and renal remission was ana?lyzed. Results Totally 30 patients had glomerular deposition of C4d. Compared with the patients without C4d deposition,the patients with C4d deposition had significantly higher levels of serum creatinine,urinary protein excretion and C4d and higher prevalence of hypertension,but had sig?nificantly decreased levels of glomerular filtration rates. With the histopathological phenotypes segregated by Lee 's classification,the ratios of C4d deposition presented an increase(P=0.005). The patients with C4d deposition had more severe mesangial proliferation,endocapillary hypercellu?larity,segmental glomerulosclerosis and tubular?interstitial injury. The rates of renal remission were significantly lower in IgA nephropathy patients with C4d deposition than those without C4d deposition(P<0.001). Conclusion IgA nephropathy patients with C4d deposition have more se?vere clinical and pathological manifestations and lower rate of renal remission. Glomerular C4d deposition is expected to be an important pathologi?cal prognostic factor for predicting the prognosis of IgA nephropathy.
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Actualmente se percibe una necesidad apremiante en la identificación y validación debiomarcadores que reflejen tempranamente el inicio de actividad lúpica o que se conviertanen predictores de la misma. La actividad clínica del lupus eritematoso sistémico (LES) esondulante a lo largo del tiempo y la actividad subyacente persistente lleva a daño tisular.Este daño es reflejo de cambios irreversibles en la función y estructura orgánica, por loque la prevención, más que el tratamiento, debería ser la meta de cualquier terapia enLES y así lograr disminuir la morbimortalidad y los costos directos e indirectos causadospor la enfermedad. Es necesario encontrar biomarcadores no invasivos de actividadlúpica que no solo permitan tomar de forma oportuna decisiones terapéuticas, sino quetambién se correlacionen con los desenlaces clínicos y sean útiles en los ensayos clínicos,permitiendo acortar el tiempo del desarrollo de estos estudios. Este artículo pretendebuscar la evidencia que se tiene con respecto a los nuevos biomarcadores existentes paraactividad de la enfermedad en LES y su utilidad actual y futura, enfatizando en la necesidadde buscar nuevas moléculas que permitan un diagnóstico más precoz de la actividad de laenfermedad.
There is a need for the identification and validation of biomarkers that reflect the early onset of lupus activity or may be predictors of this. The clinical activity of systemic lupus erythematosus (SLE) fluctuates over time and the underlying activity leads to persistent tissue damage. This damage is a reflection of irreversible changes in the function and organic structure, so prevention, rather than treatment, should be the goal of any therapy in SLE.This will reduce morbidity, mortality, direct and indirect costs caused by the disease. It is necessary to find biomarkers of lupus activity that not only allow making treatment decisions in the short term, but also to correlate with clinical outcomes. These could also be useful in clinical trials and may shorten the duration of these studies. This article aims to find evidence on new biomarkers for SLE disease activity, and their current and future use. Emphasis will be made on the need to find new molecules for an early diagnosis of disease activity.
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Humans , Antibodies , Complement C1q , Lupus Erythematosus, Systemic , Biomarkers , NucleosomesABSTRACT
Progress in the field of antibody mediated rejection (ABMR) in kidney transplantation has shown a rapid increase during the past two decades. New pathologic entities have emerged and replace old concepts and diagnostic terms. According to newly acknowledged facts discovered by clinicians, researchers, and pathologists all over the world, an updated classification, rather than Banff 07, is needed. In order to improve the diagnostic accuracy for ABMR in clinicians as well as pathologists, recognition and awareness of various conditions such as C4d-negative ABMR, subclinical ABMR, de novo donor specific antibody, microcirculation inflammation, isolated vascular lesion, antibody-mediated transplant arteriopathy, etc. are essentially important.
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Humans , Antibodies , Complement C4b , Graft Rejection , Inflammation , Kidney , Kidney Transplantation , Microcirculation , Peptide Fragments , Rejection, Psychology , Tissue Donors , TransplantsABSTRACT
Objective To observe the pathologic features on cardiac allograft and to test archived endomyocardial biopsy specimens for antibody-mediated rejection specific marker-C4d deposition and its characteristics by using immunoperoxidase (IP) techniques. Methods From January 2003 to December 2007,10 recipients underwent orthotopic cardiac transplantation and 17 specimens of endomyocardial biopsy were obtained either for a protocol basis (generally at 1 st month,3rd month,1st year and 2nd year post-transplant) and on immediate clinical indications.All specimens of endomyocardial biopsy were collected for histopathological examination and C4d immunohistochemical staining,simultaneously. All pathological diagnoses were done according to 2004 International Society for Heart and Lung Transplantation (ISHLT) recommendation working formulation and AMR Schema,and C4d staining intensity were graded and recorded as 0 to 3 +.Results Except 1 specimen unqualified,all 16 consecutive specimens of endomyocardial biopsy were qualified.There were 4 cases of acute T cell-mediated rejection (all graded 1 ),2 cases of Quilty lesion,and 7 cases of antibody-mediated rejection,who were documented according to ISHLT Schema and C4d deposition.Meanwhile,there were 6 cases showing evidence of antibody-mediated rejection without concurrent acute cellular rejection and only one case concordant with acute T cell-mediated rejection.One case of antibody-mediated rejection died 20 months posttransplantation due to combined transplant coronary artery disease (TCAD). The C4d in the cardiac allograft was deposited in microvasculature diffusively.Conclusion Antibody-mediated rejection is an important clinical entity following orthotopic heart transplantation and is difficult to diagnosis except to perform endomyoeardial biopsy.Immunoperoxidase staining for C4d is a sensitive and specific technique for detecting one marker of antibody-mediated rejection.
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Donor-specific anti-human leukocyte antigen antibodies (DSA) following kidney transplantation predict the evolution of humoral rejection and reduced graft survival. Rapid, complete elimination of DSA during antibody-mediated rejection (AMR) is rarely achieved with traditional antihumoral therapies. We report the case of a 39-year-old female who was admitted for increasing azotemia and diagnosed with AMR based on diffusely positive histological changes on C4d immunostaining. In this case, bortezomib reversed the histological changes and induced a reduction in DSA. Proteasome-inhibitor-based combination therapy is a potential means for rapid DSA elimination in antibody-mediated rejection in renal transplant recipients.
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Adult , Female , Humans , Antibodies , Azotemia , Boronic Acids , Complement C4b , Graft Survival , HLA Antigens , Kidney Transplantation , Leukocytes , Peptide Fragments , Proteasome Inhibitors , Pyrazines , Rejection, Psychology , Transplants , BortezomibABSTRACT
Donor-specific anti-human leukocyte antigen antibodies (DSA) following kidney transplantation predict the evolution of humoral rejection and reduced graft survival. Rapid, complete elimination of DSA during antibody-mediated rejection (AMR) is rarely achieved with traditional antihumoral therapies. We report the case of a 39-year-old female who was admitted for increasing azotemia and diagnosed with AMR based on diffusely positive histological changes on C4d immunostaining. In this case, bortezomib reversed the histological changes and induced a reduction in DSA. Proteasome-inhibitor-based combination therapy is a potential means for rapid DSA elimination in antibody-mediated rejection in renal transplant recipients.
Subject(s)
Adult , Female , Humans , Antibodies , Azotemia , Boronic Acids , Complement C4b , Graft Survival , HLA Antigens , Kidney Transplantation , Leukocytes , Peptide Fragments , Proteasome Inhibitors , Pyrazines , Rejection, Psychology , Transplants , BortezomibABSTRACT
Objective To investigate the effect of C4d deposition in peritubular capillary (PTC)in chronic allograft nephropathy (CAN) on prognosis and intervention of renal transplantation recipients. Methods All the cases who received the renal graft biopsy due to diagnosis of CAN from January 2000 to August 2008, and had the 2-year follow-up data were included in the study. The clinical data were analyzed according to the C4d deposition in PTC. Results Among 86 cases 39 cases were C4d positive (C4d+ group) and the remaining 47 cases were negative (C4d group). There was no significant difference in sex, age, donor source, transplant times, time after biopsy, the panel reactive antibodies (PRA) level between two groups (P＞0. 05). Before intervention, there was no significant difference in serum creatinine (Scr) and 24 h urinary protein between two groups (P＞0. 05). At the end of 2-year followed-up period, graft loss rate and urinary protein levels in C4d+group were significantly higher than in C4d- group (P＜0. 05). Before intervention, the incidence of blood lipid disorder and hypertension was higher in C4d- group (P ＜ 0. 05 ), but no significant difference was found in uric acid and blood sugar levels (P＞0. 05). At the end of 2-year followed-up period, there was no significant difference in blood glucose, uric acid, blood pressure and lipid profile (eliminating renal lost cases) between two groups (P＞0. 05). Conclusion The patients with CAN and C4d+ means the involvement of chronic humoral rejection and have poor clinical results. Effective intervention against humoral immune response can improve renal allograft survival.
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C4d deposition in peritubular capillaries in renal allograft biopsies is a significant marker for diagnosis of antibody-mediated rejection. However, it is unclear whether C4d deposition could be derived from BK virus infection. We present a case of BK virus nephropathy with strong C4d deposition 10 months after kidney transplantation. The diagnosis of BK virus nephropathy was missed out, whereas strong C4d deposition was noted in the first biopsy and therefore anti-rejection therapy was started. The deterioration of renal function led to a evaluate the possibility of BK virus nephropathy with second graft biopsy and further studies of BK virus replication status. Second graft biopsy revealed BK virus nephropathy without rejection. Finally, discontinuation of immunosuppressants and addition of anti-viral therapy for BK virus resulted in recovery of renal function, despite development of pancytopenia and subsequent fungal infection after leflunomide therapy. As in this case, initial focal pathologic changes from BK virus nephropathy could be overlooked by light microscopy. In addition, even though C4d positivity in peritubular capillaries is a good marker for diagnosis of antibody-mediated rejection, the meticulous examinations of the localization of C4d is needed, considering BK virus activates complement pathways and therefore leads to deposition of C4d mainly in tubular basement membrane. Based on our case of BK virus nephropathy with strong C4d deposition, we suggest that C4d deposition could be derived from BK virus nephropathy and therefore, it should be differentiated from acute antibody- mediated rejection in a renal allograft recipient.
Subject(s)
Basement Membrane , Biopsy , BK Virus , Capillaries , Complement C4b , Complement System Proteins , Immunosuppression Therapy , Immunosuppressive Agents , Isoxazoles , Kidney Transplantation , Light , Microscopy , Pancytopenia , Peptide Fragments , Rejection, Psychology , Transplantation, Homologous , TransplantsABSTRACT
BACKGROUND: Deposition of C4d along the peritubular capillaries is generally associated with an antibody-mediated response. We evaluated, with performing C4d immunostaining, the diagnostic accuracy of the cases that were previously diagnosed as antibody-mediated rejection (ABMR) when based only on the histologic findings, and we examined possible correlation of C4d with HLA-DR. METHODS: Forty-five renal transplantation biopsies, which showed ABMR-like histology, were obtained. The expressions of C4d and HLA-DR in the transplant rejection cases were investigated using immunofluorescent and/or immunohistochemical staining. RESULTS: There were 14 discordant cases among a total of 45 cases when C4d was used as a diagnostic marker and the original slides were reviewed. These total cases consisted of the C4d negative cases in two cases of hyperacute rejection and all the cases of ABMR and ABMR with chronic/sclerosing allograft nephropathy (CAN) and two C4d positive cases (one each of acute cellular rejection (ACR) and CAN according to their original diagnosis) and all these cases were then revised according to Banff 07. The expression of HLA-DR tended to be correlated with the log-transformed duration of grafts until three years after the transplantation. CONCLUSION: This study demonstrates that C4d together with the histologic findings should be used for making the diagnosis of ABMR. The tubular HLA-DR expression over time should be studied to further understand the mechanism of graft rejection.