Clinical Transplants

Immunoglobulin G (IgG) antibodies against donor human leukocyte antigens (HLA) are monitored in the pre-and post-transplant period due to their established role in predicting rejection and renal allograft survival. However, the role of immunoglobulin M (IgM) anti-HLA donor-specific antibodies (DSA) is not fully understood, especially in highly-sensitized patients undergoing direct transplantation. We designed this study to determine whether IgM DSA predicts rejection episodes and/or graft failure. Samples from 92 patients who had undergone HLA-antibody incompatible transplants were tested at 5 time points: days -8 (pre-plasmapheresis), 0, 7, 14, and 30 using Luminex microbead assay with ethylenediaminetetraacetic acid containing wash buffer (LABScreen®, One Lambda, Canoga Park, CA)...

The aim of this study was to determine whether the influenza vaccine induces the development of anti-human leukocyte antigen (HLA) and anti-major histocompatibility complex class I - chain A (MICA) antibodies. We determined the presence or de novo development of anti-HLA and anti-MICA antibodies in 3 groups of patients vaccinated against influenza: A) 42 healthy adults; B) 40 end-stage kidney disease patients; C) 25 kidney transplant recipients; and, D) 22 healthy adults who refused vaccination. Serum samples per subject were obtained: prior to vaccination, one week after vaccination, and on a monthly basis for 6 months...

Single antigen bead (SAB) and complement-binding assays are commonly used to monitor immunization in transplant patients. Like all new diagnostic assays, some considerations have to be appreciated to avoid a biased utilization. By truly decreasing antibody concentration, SAB monitoring in sensitized patients experiencing apheresis offers a good opportunity to explore analytical interference. We explored analytical artifacts by analyzing the role of prozone and saturation effects through a concrete example of a single patient who experienced immunoadsorption...

The highly-sensitized kidney transplant candidate with no available living donors remains at a major disadvantage with decreased access and worse outcomes post-transplant. We have previously reported our initial data on both pre-transplant and post-transplant desensitization. We observed only a modest decline in unacceptable antigens with pretransplant intravenous immunoglobin (IVIG) and rituximab. Due to these observations, we have focused on a peri-operative post-transplant desensitization protocol in our program...

Acute rejection in human leukocyte antigen (HLA)-matched kidney transplant recipients is uncommon and the mechanisms involved are not well understood. Data from 6-antigen HLA-matched recipients transplanted between 1994 and 2014 were analyzed to identify the incidence, risk factors, and outcomes associated with biopsy-proven acute rejection (BPAR). A total of 278 HLA-matched recipients were identified, of which, 155 (55.8%) received a graft from a sibling donor. Ten patients (3.6%) experienced BPAR over a median follow-up of 10 years (0...

Donor-specific anti-human leukocyte antigen antibodies (DSA) are associated with antibody-mediated rejection (AMR) in kidney transplantation, but the spectrum of graft injury seen in patients with DSA ranges from no damage to florid rejection. Since immunoglobulin G (IgG) antibodies with cytotoxic potential can be distinguished by their binding complement fraction C1q, the level of C1q-binding IgG (C1q+) DSA may be useful for stratifying risk or diagnosing AMR. We therefore investigated the value of IgG and C1q+ DSA in predicting pathologic features of AMR on kidney biopsies...

Recent literature suggests that a positive crossmatch adversely impacts outcomes in simultaneous liver-kidney transplant (SLKT). The aim of this study was to evaluate outcomes of SLKT with a positive flow crossmatch (+FCXM) at our center. We retrospectively analyzed all of the SLKTs between January 1, 2000, and September 30, 2010. A total of 2793 kidney transplants and 892 liver transplants were performed in this time period, of which, 31 were SLKT (3%). Seven of the 31 (22%) SLKTs had a +FCXM. There were 3 major adverse events: 1 patient mortality at 9 months with liver failure; 1 allograft nephrectomy for primary nonfunction secondary to hyper-acute rejection; and, 1 recurrent liver allograft rejection with eventual graft loss and death at 26 months post-transplant...

Development of acute antibody-mediated rejection (AMR) is associated with graft loss and can occur both early (<3 months) and late (>3 months) post-transplant. Treatment and prognosis differ in early and late AMR. Herein, we present a single-center experience using high-dose intravenous immunoglobulin (IVIg) (2g/kg) for the treatment of late AMR. All kidney recipients with negative T- and B-cell flow crossmatch at transplant and biopsy-proven late AMR were included (2009-2013, n=126). All patients were treated with IVIg at 2g/kg over divided doses and high-dose intravenous methylprednisolone...

BK polyomavirus infection and de novo donor-human leukocyte antigen (HLA) specific antibodies (dnDSA) are two well-known and distinct complications occurring after kidney transplantation. Recent literature suggests an association between the two events. This study aims to examine the relationship between BK viremia (BKV) and dnDSA and to identify potential risk factors for dnDSA following BKV in kidney transplant recipients. A retrospective review of 1019 recipients from Houston Methodist Hospital was conducted...

Antibody-mediated rejection (AMR) remains a problem without a reliable treatment in the care of kidney transplant patients. We proposed and tested a program of screening for donor specific antibodies (DSA) to initiate treatment of patients before AMR was detected and to prevent its occurrence. Starting in April 2012, we stratified patients into high-, medium-, and low-risk groups for the development of DSA and instituted a program of screening for and treatment of these antibodies. We used a historic control group of patients transplanted at our center as a comparator and looked at rates of DSA testing and development as well as rates of development of AMR, cell-mediated rejection, and graft loss...

The relationship between circulating pre-transplant immunoglobulin G (IgG) antibodies to donor human leukocyte antigen (HLA) -C locus determined antigens alone and acute rejection, kidney allograft function, and graft survival is not fully defined. Also, the impact of circulating pre-transplant IgG antibodies to donor HLA-C locus antigens alone on these outcomes has not been compared with the impact of circulating pre-transplant IgG antibodies to donor HLA-A or -B locus antigens. We conducted a retrospective review of records of 1252 kidney allograft recipients transplanted at our center between January 2010 and January 2016 to identify patients with circulating pre-transplant IgG antibodies directed at kidney donor HLA-A, -B, or -C locus determined antigens...

We report three interesting cases concerning antibody-mediated rejection (AMR), associated or not with anti-donor-specific antibodies, and detection of implicated molecular epitopes. The first report presents a case of intra-allele sensitization. The second case presents an interesting case concerning Luminex mean fluorescence intensity (MFI) levels considered to be low risk antibodies (<1000), but producing AMR. The third case occurred after a second kidney transplantation mediated by antibodies directed against HLA-C antigens (MFI<1000) in the previous transplantation (which was considered to be an indicator of low-risk of AMR)...

A significant barrier to long-term transplant success is the development of de novo donor-specific human leukocyte antigen (HLA) antibodies. The best approach to minimize the risk of developing such antibodies is an HLA identical transplant, but the likelihood of finding such an organ is very low. The alternative is to identify "permissible mismatches" - HLA antigen mismatches that are less likely to induce an immune response. In the past few years, it has become clear that matching at the "epitope level" is the likely solution; however, we are still struggling with how to define HLA epitopes...

Organ transplantation overcomes conservative therapy to improve patient longevity. Despite the improvement of donor-recipient compatibility tests and intensified immunosuppressive agents, long-term graft survival remains poor because of acute and chronic injury driven by immunologic and non-immunologic factors. The significant immunological barrier for graft longevity is antibody-mediated rejection. Antibodies reactive to donor-specific human leukocyte antigens (HLA) have been shown to have adverse effects on the transplanted organ...

Antibody-mediated rejection in solid organ transplantation is associated with significant organ dysfunction and allograft loss. Donor-specific antibodies against human leukocyte antigens (HLAs) have been a major focus for research, clinical testing, and therapies. Recently, non-HLA autoantibodies to various endothelial antigens including angiotensin II type 1 receptor, endothelin-1 type A receptor, Major Histocompatibility Complex Class 1-Related Chain A, perlecan, and collagen V are emerging as both potential mediators of allograft dysfunction and targets for intervention...

Poor long-term graft survival remains a major problem in the field of organ transplantation. This could be attributed at least in part, to the lack of reliable biomarkers that allow for accurate, noninvasive monitoring of graft status and individualized immunosuppressive therapy. To this end, cytokines and chemokines have been investigated in a number of studies to evaluate their potential to serve as diagnostic and prognostic markers for kidney transplantation. Based on our review of recent publications, urinary chemokine C-C motif ligand 2, chemokine C-XC motif ligand (CXCL) 9, and CXCL10 are identified as potential novel biomarkers of renal graft outcomes...

The results from continued research regarding the role of anti-human leukocyte antigen (anti-HLA) antibodies and donor-specific antibodies (DSA) in transplantation has strengthened the association between DSA and allograft rejection. The formation of de novo DSAs is particularly detrimental to allograft function and survival. Paradoxically, grafts of patients without DSA may fail and patients with DSA may continue to have extended post-transplant graft function. An explanation for this inconsistency in outcomes must be found to utilize anti-HLA DSA as a biomarker of allograft rejection...

Long-term outcomes for pediatric patients with intestinal failure have significantly improved with advances in management of parenteral nutrition and the associated comorbidities. These changes have been driven by the development of multidisciplinary intestinal rehabilitation teams. Overall survival and transplant-free survival rates have increased while the introduction of new management strategies has decreased complications such as central line infections and intestinal failure associated liver disease. Factors have been identified that aid in prediction of duration of parenteral nutrition and time to enteral autonomy...

This review summarizes bioengineering innovations in the treatment of patients with short bowel syndrome. Bioengineering approaches aim to increase the overall intestinal tissue mass. While the morphology of the intestine is clearly altered by these interventions, it remains to be shown that the overall function of the intestine is improved. Continued innovations will likely bring about new therapeutic options for patients with short bowel syndrome. Careful evaluations of the impact of these interventions await controlled clinical trials...

BACKGROUND: Human leukocyte antigen (HLA) antibodies are a major cause of graft loss in mismatched transplant recipients. However, the time to graft loss resulting from antibody induced injury is unpredictable. The unpredictable nature of antibodies may be related to the subclass of antibodies. In this study, HLA immunoglobulin G (IgG) subclasses were investigated to determine whether a unique IgG subclass composition could better identify those patients at eminent risk for graft loss...