Application, technical issues, and interpretation of C1q for graft outcome

Tyan, Dolly B.

doi:10.1097/mot.0000000000000454

Cited by 9 publications

(11 citation statements)

References 34 publications

(41 reference statements)

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“…Moreover, the SAB assays can be falsely low, while the C1q assay is more accurate. Therefore, the SAB assay has limitations that mislead the interpretation in comparing MFI versus C1q, C3d, or C4d assays [ 73 ]. In contrast to MFI that was reported in most of the studies in this meta-analysis, anti-HLA DSA level determined by titer of antibody correlated with complement-fixing ability [ 22 , 74 ].…”

Section: Discussionmentioning

confidence: 99%

Complement-activating donor-specific anti-HLA antibodies and solid organ transplant survival: A systematic review and meta-analysis

et al. 2018

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BackgroundAnti-human leukocyte antigen donor-specific antibodies (anti-HLA DSAs) are recognized as a major barrier to patients’ access to organ transplantation and the major cause of graft failure. The capacity of circulating anti-HLA DSAs to activate complement has been suggested as a potential biomarker for optimizing graft allocation and improving the rate of successful transplantations.Methods and findingsTo address the clinical relevance of complement-activating anti-HLA DSAs across all solid organ transplant patients, we performed a meta-analysis of their association with transplant outcome through a systematic review, from inception to January 31, 2018. The primary outcome was allograft loss, and the secondary outcome was allograft rejection. A comprehensive search strategy was conducted through several databases (Medline, Embase, Cochrane, and Scopus).A total of 5,861 eligible citations were identified. A total of 37 studies were included in the meta-analysis. Studies reported on 7,936 patients, including kidney (n = 5,991), liver (n = 1,459), heart (n = 370), and lung recipients (n = 116). Solid organ transplant recipients with circulating complement-activating anti-HLA DSAs experienced an increased risk of allograft loss (pooled HR 3.09; 95% CI 2.55–3.74, P = 0.001; I2 = 29.3%), and allograft rejection (pooled HR 3.75; 95% CI: 2.05–6.87, P = 0.001; I2 = 69.8%) compared to patients without complement-activating anti-HLA DSAs. The association between circulating complement-activating anti-HLA DSAs and allograft failure was consistent across all subgroups and sensitivity analyses. Limitations of the study are the observational and retrospective design of almost all included studies, the higher proportion of kidney recipients compared to other solid organ transplant recipients, and the inclusion of fewer studies investigating allograft rejection.ConclusionsIn this study, we found that circulating complement-activating anti-HLA DSAs had a significant deleterious impact on solid organ transplant survival and risk of rejection. The detection of complement-activating anti-HLA DSAs may add value at an individual patient level for noninvasive biomarker-guided risk stratification.Trial registrationNational Clinical Trial protocol ID: NCT03438058.

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Section: Discussionmentioning

confidence: 99%

Complement-activating donor-specific anti-HLA antibodies and solid organ transplant survival: A systematic review and meta-analysis

et al. 2018

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“…Our study shows higher risk of all‐cause mortality and composite outcome in recipients with C1q binding DSA. According to the unfavorable results described in the KTA literature and for other solid organ , the circulating C1q+DSA can theoretically cause kidney allograft injury. Hence, C1q+DSA, especially its post‐transplant form, might be a new target of immunologic risk assessment in SLKT.…”

Section: Discussionmentioning

confidence: 99%

Association between post‐transplant donor‐specific antibodies and recipient outcomes in simultaneous liver–kidney transplant recipients: single‐center, cohort study

et al. 2019

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There is a dearth of published data regarding the presence of post-transplant donor-specific antibodies (DSA), especially C1q-binding DSA (C1q+DSA), and patient and kidney allograft outcomes in simultaneous liver-kidney transplant (SLKT) recipients. We conducted a retrospective cohort study consisted of 85 consecutive SLKT patients between 2009 and 2018 in our center. Associations between presence of post-transplant DSA, including persistent and/or newly developed DSA and C1q+DSA, and all-cause mortality and the composite outcome of mortality, allograft kidney loss, and antibody-mediated rejection were examined using unadjusted and age and sex-adjusted Cox proportional hazards and time-dependent regression models. The mean age at SLKT was 56 years and 60% of the patients were male. Twelve patients (14%) had post-transplant DSA and seven patients (8%) had C1q+DSA. The presence of post-transplant DSA was significantly associated with increased risk of mortality (unadjusted model: Hazard Ratio (HR) = 2.72, 95% confidence interval (CI): 1.06-6.98 and adjusted model: HR = 3.20, 95% CI: 1.11-9.22) and the composite outcome (unadjusted model: HR = 3.18, 95% CI: 1.31-7.68 and adjusted model: HR = 3.93, 95% CI: 1.39-11.10). There was also higher risk for outcomes in recipients with C1q+DSA compared the ones without C1q+DSA. Post-transplant DSA is significantly associated with worse patient and kidney allograft outcomes in SLKT. Further prospective and large cohort studies are warranted to better assess these associations.

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“… 33 Additionally, the C1q assay provides a yes or no answer for complement binding and may be more time and cost efficient than other titration assays using serial dilutions. 34 We therefore chose the C1q assay as the surrogate marker of responsiveness to the desensitization treatment in the current study. Prospective studies to address this issue are ongoing.…”

Section: Discussionmentioning

confidence: 99%

Treatment of allosensitized patients receiving allogeneic transplantation

et al. 2021

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Donor-specific anti-HLA antibodies (DSA) are a major cause of engraftment failure in patients receiving haploidentical stem cell transplantation (HaploSCT). Effective treatments are needed for these patients who often have no other donor options and/or are in need to proceed urgently to transplantation. We studied a multimodality treatment with alternate day plasma exchange, rituximab, intravenous gamma globulin (IvIg) and an irradiated donor buffy coat for patients with DSA at two institutions. Thirty-seven patients with a median age of 51 years were treated with this desensitization protocol. Treatment outcomes were compared with a control group of HaploSCT patients without DSA (N=345). Majority of patients in the DSA group were females (83.8% vs. 37.1% in controls, p<0.001) and received stem cells from a child as donor (67.6% vs. 44.1%, p=0.002). Mean DSA level before and after desensitization was 10,198 and 5,937 MFI, respectively with mean differences of 4,030 MFI. Fourteen of 30 tested patients (46.7%) had C1q positivity while 8 of 29 tested patients (27.6%) remained positive after desensitization. In multivariable analysis, patients with initial DSA >20,000 MFI and with persistent C1q+ after desensitization had a significantly lower engraftment rate, resulted in a significantly higher non-relapse mortality (NRM) and worse overall survival (OS) than controls whereas graft outcome and survivals of patients with initial DSA <20,000 MFI and those with negative C1q after treatment were comparable with controls. In conclusion, treatment with plasma exchange, rituximab, IvIg and donor buffy coat is effective in promoting engraftment in patients with DSA up to 20,000 MFI.

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Application, technical issues, and interpretation of C1q for graft outcome

Cited by 9 publications

References 34 publications

Complement-activating donor-specific anti-HLA antibodies and solid organ transplant survival: A systematic review and meta-analysis

Complement-activating donor-specific anti-HLA antibodies and solid organ transplant survival: A systematic review and meta-analysis

Association between post‐transplant donor‐specific antibodies and recipient outcomes in simultaneous liver–kidney transplant recipients: single‐center, cohort study

Treatment of allosensitized patients receiving allogeneic transplantation

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