Serum complement inactivation unveiled prepregnancy donor-specific HLA antibodies leading to postpartum kidney graft loss

Nocera, Arcangelo; Cioni, Michela; Tagliamacco, Augusto; Comoli, Patrizia; Innocente, Annalisa; Ceriolo, Paola; Cardillo, Massimo; Ginevri, Fabrizio

doi:10.1111/tri.12521

Cited by 2 publications

(2 citation statements)

References 8 publications

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“…Single antigen results above an MFI cut‐off value of 1000 were considered positive. Before testing, all sera were pretreated with disodium EDTA (final concentration 10 mmol/L, pH 7.4; Sigma‐Aldrich, Milan, Italy) , to rule out underestimation of antibody MFI strength due to complement interference that can resemble a prozone effect .…”

Section: Methodsmentioning

confidence: 99%

Kidney Intragraft Homing of De Novo Donor-Specific HLA Antibodies Is an Essential Step of Antibody-Mediated Damage but Not Per Se Predictive of Graft Loss

Nocera

Tagliamacco

Cioni

et al. 2017

American Journal of Transplantation

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Donor-specific HLA antibody (DSA)-mediated graft injury is the major cause of kidney loss. Among DSA characteristics, graft homing has been suggested as an indicator of severe tissue damage. We analyzed the role of de novo DSA (dnDSA) graft homing on kidney transplantation outcome. Graft biopsy specimens and parallel sera from 48 nonsensitized pediatric kidney recipients were analyzed. Serum samples and eluates from graft biopsy specimens were tested for the presence of dnDSAs with flow bead technology. Intragraft dnDSAs (gDSAs) were never detected in the absence of serum dnDSAs (sDSAs), whereas in the presence of sDSAs, gDSAs were demonstrated in 72% of biopsy specimens. A significantly higher homing capability was expressed by class II sDSAs endowed with high mean fluorescence intensity and C3d- and/or C1q-fixing properties. In patients with available sequential biopsy specimens, we detected gDSAs before the appearance of antibody-mediated rejection. In sDSA-positive patients, gDSA positivity did not allow stratification for antibody-mediated graft lesions and graft loss. However, a consistent detection of skewed unique DSA specificities was observed over time within the graft, likely responsible for the damage. Our results indicate that gDSAs could represent an instrumental tool to identify, among sDSAs, clinically relevant antibody specificities requiring monitoring and possibly guiding patient management.

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Section: Methodsmentioning

confidence: 99%

Kidney Intragraft Homing of De Novo Donor-Specific HLA Antibodies Is an Essential Step of Antibody-Mediated Damage but Not Per Se Predictive of Graft Loss

Nocera

Tagliamacco

Cioni

et al. 2017

American Journal of Transplantation

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“…Anti-HLA class I and class II IgG antibodies were tested with a bead-based detection assay after serum EDTA treatment, to avoid underestimation of antibody MFI strength [23–25]. We used the LABScreen Mixed kit and the Single-Antigen Bead (SAB) assays (One Lambda Inc., CA, USA) to identify HLA class I and class II specificities [12, 22].…”

Section: Methodsmentioning

confidence: 99%

De Novo Donor-Specific HLA Antibodies Developing Early or Late after Transplant Are Associated with the Same Risk of Graft Damage and Loss in Nonsensitized Kidney Recipients

Cioni

Nocera

Innocente

et al. 2017

Journal of Immunology Research

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De novo posttransplant donor-specific HLA-antibody (dnDSA) detection is now recognized as a tool to identify patients at risk for antibody-mediated rejection (AMR) and graft loss. It is still unclear whether the time interval from transplant to DSA occurrence influences graft damage. Utilizing sera collected longitudinally, we evaluated 114 consecutive primary pediatric kidney recipients grafted between 2002 and 2013 for dnDSA occurrence by Luminex platform. dnDSAs occurred in 39 patients at a median time of 24.6 months. In 15 patients, dnDSAs developed within 1 year (early-onset group), while the other 24 seroconverted after the first posttransplant year (late-onset group). The two groups were comparable when considering patient- and transplant-related factors, as well as DSA biological properties, including C1q and C3d complement-binding ability. Only recipient age at transplant significantly differed in the two cohorts, with younger patients showing earlier dnDSA development. Late AMR was diagnosed in 47% of the early group and in 58% of the late group. Graft loss occurred in 3/15 (20%) and 4/24 (17%) patients in early- and late-onset groups, respectively (p = ns). In our pediatric kidney recipients, dnDSAs predict AMR and graft loss irrespective of the time elapsed between transplantation and antibody occurrence.

show abstract

Serum complement inactivation unveiled prepregnancy donor-specific HLA antibodies leading to postpartum kidney graft loss

Cited by 2 publications

References 8 publications

Kidney Intragraft Homing of De Novo Donor-Specific HLA Antibodies Is an Essential Step of Antibody-Mediated Damage but Not Per Se Predictive of Graft Loss

Kidney Intragraft Homing of De Novo Donor-Specific HLA Antibodies Is an Essential Step of Antibody-Mediated Damage but Not Per Se Predictive of Graft Loss

De Novo Donor-Specific HLA Antibodies Developing Early or Late after Transplant Are Associated with the Same Risk of Graft Damage and Loss in Nonsensitized Kidney Recipients

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