The role of complement‐fixing donor‐specific antibodies identified by a C1q assay after heart transplantation

Farrero, Marta; Pando, Marcelo J.; Luo, Chwan Yau; Luikart, Helen; Valantine, Hannah A.; Khush, Kiran K.

doi:10.1111/ctr.13121

Cited by 20 publications

(19 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We found the presence of preformed IgG+ DSA at transplant to be associated with pAMR development, as has been reported by others; however, we also observed that 86% of patients who developed pAMR2 had new C1q+ DSA at the time of diagnosis, supporting the hypothesis that complement fixation plays an important role in the pathology of pAMR . It is possible that the lower incidence of AMR in this study is the result of our institutional policy to ensure a C1q‐DSA‐negative VXM at the time of donor acceptance, although further study is warranted.…”

Section: Discussionsupporting

confidence: 89%

Pathological antibody‐mediated rejection in pediatric heart transplant recipients: Immunologic risk factors, hemodynamic significance, and outcomes

Hollander

Peng

Mills

et al. 2018

Pediatric Transplantation

View full text Add to dashboard Cite

Biopsy-diagnosed pAMR has been observed in over half of pediatric HT recipients within 6 years of transplantation. We report the incidence and outcomes of pAMR at our center. All endomyocardial biopsies for all HT recipients transplanted between 2010 and 2015 were reviewed and classified using contemporary ISHLT guidelines. Graft dysfunction was defined as a qualitative decrement in systolic function by echocardiogram or an increase of ≥3 mm Hg in atrial filling pressure by direct measurement. Among 96 patients, pAMR2 occurred in 7 (7%) over a median follow-up period of 3.1 years, while no cases of pAMR3 occurred. A history of CHD, DSA at transplant, and elevated filling pressures were associated with pAMR2. Five-sixths (83%) of patients developed new C1q+ DSA at the time of pAMR diagnosis. There was a trend toward reduced survival, with 43% of patients dying within 2.3 years of pAMR diagnosis.

show abstract

Section: Discussionsupporting

confidence: 89%

Pathological antibody‐mediated rejection in pediatric heart transplant recipients: Immunologic risk factors, hemodynamic significance, and outcomes

Hollander

Peng

Mills

et al. 2018

Pediatric Transplantation

View full text Add to dashboard Cite

show abstract

“…The reason for this significant difference in age is unclear, with similar findings in other studies relating to both heart and kidney transplantation. 23 , 24 The frequency of antibodies targeting HLA class II antigens compared to HLA class I was statistically significant ( P =.005), a phenomenon which was previously reported by other investigators. 16 , 22 The literature also shows a higher proportion of antibodies targeting the HLA-DQ and DR antigens, 16 , 22 which was also demonstrated during our analysis, particularly with regards to HLA-DQ.…”

Section: Discussionsupporting

confidence: 80%

Donor–specific HLA-DQ antibodies may contribute to poor graft outcome after heart transplantation

Omrani¹,

Al-Awwami

Buraiki

et al. 2018

Annals of Saudi Medicine

View full text Add to dashboard Cite

BACKGROUNDHLA-DQ donor-specific antibodies (DSA) are implicated in allograft dysfunction after renal and lung transplantation. Limited data exists on the impact of HLA-DQ antibodies on heart transplant patients.OBJECTIVETo investigate the impact of DSA formation on allograft function and outcomes in heart transplant patients.DESIGNRetrospective cohort study.SETTINGCollating post-transplantation patient data from computerized database in a tertiary hospital in Riyadh, Saudi Arabia from January 2006 to October 2014.PATIENTS AND METHODSWe excluded recipients with positive preoperative complement-dependent-cytotoxicity crossmatch grafts and those with preformed DSA. Anti-HLA antibodies were identified using Luminex-based assay in sera collected before transplantation with a routine endomyocardial biopsy the first year and then annually.MAIN OUTCOME MEASURESPrimary outcome measures were all-cause mortality, development of antibody mediated rejection, treated acute cellular rejection (ACR) and cardiac allograft vasculopathy (CAV).SAMPLE SIZE127 patients.RESULTSDSA formation occurred in 43/127 (34%), with 33/43 (77%) targeting HLA-DQ antigens alone (n=7) or in combination with -DR, -A or B antibodies (n=26). Most (76%) were male and the mean (SD) age was 36 (14) years. Ten patients developed -A, -B or -DR antibodies without -DQ antibodies also present. Treated ACR (P=.011), reduced left ventricular ejection fraction (P<.001), CAV development (P=.003), and all-cause mortality (P=.01) were all significantly more prevalent in the DSA-positive cohort.CONCLUSIONHLA-DQ donor-specific antibodies were the most common type detected and may play a significant role in poor outcomes post-cardiac transplantation. This emphasizes the importance of HLA-DQ matching and monitoring for DSA formation in order to minimize post-transplantation immunological risk.LIMITATIONSRetrospective design comes with inherent biases, results from single institute, with a particularly young cohort.

show abstract

“…A multitude of factors contribute to accelerated allograft rejection in allosensitized recipients, such as acute complement fixation by preformed DSAs 40‐42 and rapid memory cell recall responses 43‐46 . In the present investigation, we employed a sensitized mouse model of islet transplantation to (1) investigate underlying antidonor immune responses driving islet allograft rejection in sensitized recipients and (2) devise a donor apoptotic cell–based combination regimen that promotes long‐term allograft survival in these recipients.…”

Section: Discussionmentioning

confidence: 99%

Donor apoptotic cell–based therapy for effective inhibition of donor-specific memory T and B cells to promote long-term allograft survival in allosensitized recipients

Dangi

Lee

et al. 2020

American Journal of Transplantation

View full text Add to dashboard Cite

Recipient allosensitization is a potential barrier to transplantation. 1 Blood transfusions, prior transplantation, and pregnancies may all result in allospecific memory T and B cells as well as antibodies. 2 In contrast to naïve T cells, memory T cells have a low activation threshold and thus are capable of mounting a rapid and exaggerated immune response when restimulated. 3,4 Additionally, memory B cells and preformed alloantibodies can also mediate allograft rejection. 5,6 Memory B cell differentiation has been associated with a rapid recall antibody

show abstract

The role of complement‐fixing donor‐specific antibodies identified by a C1q assay after heart transplantation

Abstract: Routine monitoring of DSA post-transplant, and their characterization using the C1q assay, may provide prognostic information for acute rejection after heart transplantation.

Cited by 20 publications

References 41 publications

Pathological antibody‐mediated rejection in pediatric heart transplant recipients: Immunologic risk factors, hemodynamic significance, and outcomes

Pathological antibody‐mediated rejection in pediatric heart transplant recipients: Immunologic risk factors, hemodynamic significance, and outcomes

Donor–specific HLA-DQ antibodies may contribute to poor graft outcome after heart transplantation

Donor apoptotic cell–based therapy for effective inhibition of donor-specific memory T and B cells to promote long-term allograft survival in allosensitized recipients

Contact Info

Product

Resources

About