Frequency of MIC Antibody in Rejected Renal Transplant Patients without HLA Antibody

Mizutani, Kazuo; Terasaki, Paul I.; Shih, Remi; Pei, Rui; Ozawa, Miyuki; Lee, Jar-How

doi:10.1016/j.humimm.2006.02.007

Cited by 66 publications

(50 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Anti-MICA Abs have been associated with renal allograft dysfunction, rejection, and graft failure in adults [26][27][28][29] ; however, anti-MICA Abs are not routinely measured in clinical practice. We found similar association of de novo MICA Ab development with AR in our single-center cohort (P=0.03), and patients who developed graft loss also had increased titers of MICA Abs detected before graft loss.…”

Section: Discussionmentioning

confidence: 99%

The Clinical Impact of Humoral Immunity in Pediatric Renal Transplantation

Chaudhuri

Ozawa

Everly

et al. 2013

Journal of the American Society of Nephrology

Self Cite

View full text Add to dashboard Cite

The development of anti-donor humoral responses after transplantation associates with higher risks for acute rejection and 1-year graft survival in adults, but the influence of humoral immunity on transplant outcomes in children is not well understood. Here, we studied the evolution of humoral immunity in lowrisk pediatric patients during the first 2 years after renal transplantation. Using data from 130 pediatric renal transplant patients randomized to steroid-free (SF) or steroid-based (SB) immunosuppression in the NIH-SNSO1 trial, we correlated the presence of serum anti-HLA antibodies to donor HLA antigens (donorspecific antibodies) and serum MHC class 1-related chain A (MICA) antibody with both clinical outcomes and histology identified on protocol biopsies at 0, 6, 12, and 24 months. We detected de novo antibodies after transplant in 24% (23% of SF group and 25% of SB group), most often after the first year. Overall, 22% developed anti-HLA antibodies, of which 6% were donor-specific antibodies, and 6% developed anti-MICA antibody. Presence of these antibodies de novo associated with significantly higher risks for acute rejection (P=0.02), chronic graft injury (P=0.02), and decline in graft function (P=0.02). In summary, antibodies to HLA and MICA antigens appear in approximately 25% of unsensitized pediatric patients, placing them at greater risk for acute and chronic rejection with accelerated loss of graft function. Avoiding steroids does not seem to modify this incidence. Whether serial assessments of these antibodies after transplant could guide individual tailoring of immunosuppression requires additional study.

show abstract

Section: Discussionmentioning

confidence: 99%

The Clinical Impact of Humoral Immunity in Pediatric Renal Transplantation

Chaudhuri

Ozawa

Everly

et al. 2013

Journal of the American Society of Nephrology

Self Cite

View full text Add to dashboard Cite

show abstract

“…5 MICA antigens are polymorphic and elicit antibody production after solid organ transplantation, which may be associated with organ allograft rejection. 6,7 MICA products are expressed constitutively in gut epithelium, endothelial cells, and fibroblasts and induced by stress in other cell types. 2,8,9 Because MICA gene products are augmented by stress in epithelia 10 and are recognized by a subpopulation of intestinal ␥␦ T cells, 11 they may play a role in triggering aGVHD.…”

Section: Introductionmentioning

confidence: 99%

Donor-recipient mismatches in MHC class I chain-related gene A in unrelated donor transplantation lead to increased incidence of acute graft-versus-host disease

Parmar

Lima

Zou

et al. 2009

Blood

View full text Add to dashboard Cite

The polymorphic products of major histocompatibility complex class I-related chain A (MICA) genes are important in solid organ transplantation rejection. MICA expression is limited to gut epithelium and may play a role in triggering acute graft-versus-host disease (aGVHD). A total of 236 recipients of unrelated donor transplantation were studied. Donor-recipient human leukocyte antigen (HLA) match was 10/10 human leukocyte antigen (HLA-A, -B, -C, -DRB1, -DQB1) in 73% and MICA mismatch in 8.4%. Because of physical vicinity of the loci, MICA mismatch was significantly associated with mismatch at HLA-B and HLA-C. A higher rate of grade II-IV aGVHD was seen in MICA-mismatched patients (80% vs 40%, P ‫؍‬ .003) irrespective of degree of HLA matching (HLA 10/10 match: 75% vs 39%, P ‫؍‬ .02) and HLA any mismatch (83% vs 46%, P ‫؍‬ .003). The rate of grade II-IV gastrointestinal aGVHD was also higher in MICA-mismatched patients (35% vs 17%, P ‫؍‬ .05). We conclude that MICA may represent novel a transplantation antigen recognized by human allogeneic T cells. This study was registered at ClinicalTrials.gov (Identifier NCT00506922).

show abstract

“…The presence of antibodies against these antigens has been demonstrated to be associated with inferior kidney graft outcomes (Rebellato et al, 2006). Relatively high frequencies (26%) of anti-MICA antibodies have been reported in recipients with anti-HLA antibodies who lost their kidney grafts because of AMR (Mizutani et al, 2005;Mizutani et al, 2006). In summary, non-HLA antigens are expressed on graft EC but not on lymphocytes, which are routinely used for CM.…”

Section: Antibodies Against Mhc Class I Chain-related Antigens (Mic)mentioning

confidence: 99%

“…Yet, how strong must the DSA signal that is produced by a SA Luminex assay be to generate a positive FCCM? In order to address this question, correlation analyses between MFI values that are detected by SA beads and signals that are detected by lymphocyte FCCM must be performed (Lobashevsky & Higgins, 2009;Martin et al, 2003;Mizutani et al, 2006;Ozawa et al, 2006;Poli et al, 2009;Qasi Y et al, 2006;Stegall et al, 2009;Zachary et al, 2005Zachary et al, , 2009). At our transplant center, the positive MFI thresholds for anti-HLA class I and class II antibodies, which are detected via SA technology and produce positive FCCMs, are 2800 and 3500, respectively (predictive value >95%) (Figure 6).…”

Section: Solid-phase Alloantibody Analysismentioning

confidence: 99%

Characteristics, Detection, and Clinical Relevance of Alloantibodies in Kidney Transplantation

Lobashevsky¹

2011

Kidney Transplantation - New Perspectives

View full text Add to dashboard Cite

Frequency of MIC Antibody in Rejected Renal Transplant Patients without HLA Antibody

Cited by 66 publications

References 16 publications

The Clinical Impact of Humoral Immunity in Pediatric Renal Transplantation

The Clinical Impact of Humoral Immunity in Pediatric Renal Transplantation

Donor-recipient mismatches in MHC class I chain-related gene A in unrelated donor transplantation lead to increased incidence of acute graft-versus-host disease

Characteristics, Detection, and Clinical Relevance of Alloantibodies in Kidney Transplantation

Contact Info

Product

Resources

About