13 results
Filters • 1
Sort By
Results Per Page
Filters
13 results
1
Download the following citations:
Email the following citations:
Print the following citations:
  • Battle R
  • Pritchard D
  • Peacock S
  • Hastie C
  • Worthington J
  • et al.
Int J Immunogenet. 2023 Nov;50 Suppl 2:3-63 doi: 10.1111/iji.12641.

Solid organ transplantation represents the best (and in many cases only) treatment option for patients with end-stage organ failure. The effectiveness and functioning life of these transplants has improved each decade due to surgical and clinical advances, and accurate histocompatibility assessment. Patient exposure to alloantigen from another individual is a common occurrence and takes place through pregnancies, blood transfusions or previous transplantation. Such exposure to alloantigen's can lead to the formation of circulating alloreactive antibodies which can be deleterious to solid organ transplant outcome. The purpose of these guidelines is to update to the previous BSHI/BTS guidelines 2016 on the relevance, assessment, and management of alloantibodies within solid organ transplantation.

  • Al-Awadhi S
  • Raynaud M
  • Louis K
  • Bouquegneau A
  • Taupin JL
  • et al.
Front Immunol. 2023 Oct 2;14:1265796 doi: 10.3389/fimmu.2023.1265796.
INTRODUCTION:

Several studies have investigated the impact of circulating complement-activating anti-human leukocyte antigen donor-specific antibodies (anti-HLA DSAs) on organ transplant outcomes. However, a critical appraisal of these studies and a demonstration of the prognostic value of complement-activating status over anti-HLA DSA mean fluorescence intensity (MFI) level are lacking.

METHODS:

We conducted a systematic review, meta-analysis and critical appraisal evaluating the role of complement-activating anti-HLA DSAs on allograft outcomes in different solid organ transplants. We included studies through Medline, Cochrane, Scopus, and Embase since inception of databases till May 05, 2023. We evaluated allograft loss as the primary outcome, and allograft rejection as the secondary outcome. We used the Newcastle-Ottawa Scale and funnel plots to assess risk of bias and used bias adjustment methods when appropriate. We performed multiple subgroup analyses to account for sources of heterogeneity and studied the added value of complement assays over anti-HLA DSA MFI level.

RESULTS:

In total, 52 studies were included in the final meta-analysis (11,035 patients). Complement-activating anti-HLA DSAs were associated with an increased risk of allograft loss (HR 2.77; 95% CI 2.33-3.29, p<0.001; I²=46.2%), and allograft rejection (HR 4.98; 95% CI 2.96-8.36, p<0.01; I²=70.9%). These results remained significant after adjustment for potential sources of bias and across multiple subgroup analyses. After adjusting on pan-IgG anti-HLA DSA defined by the MFI levels, complement-activating anti-HLA DSAs were significantly and independently associated with an increased risk of allograft loss.

DISCUSSION:

We demonstrated in this systematic review, meta-analysis and critical appraisal the significant deleterious impact and the independent prognostic value of circulating complement-activating anti-HLA DSAs on solid organ transplant risk of allograft loss and rejection.

  • Khan SM
  • Sumbal R
  • Schenk AD
Transplant Proc. 2021 Dec;53(10):3022-3029 doi: 10.1016/j.transproceed.2021.08.052.
BACKGROUND:

The aim of this review is to provide consensus on the impact of antihuman leukocyte antigen (anti-HLA) de novo donor-specific antibodies (dnDSA) on pancreatic allograft loss.

METHODS:

We systematically searched electronic databases through August 2020 using Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology. Articles that provided or allowed estimation of the odds ratio (OR) and 95% confidence interval (CI) for pancreatic allograft loss in patients with and without anti-HLA dnDSA were included.

RESULTS:

Eight studies with a total of 1434 patients were included. Patients with anti-HLA dnDSA had significantly higher odds of graft failure (OR = 4.42, 95% CI [3.15-6.22], I2 = 38%). Pooled data on graft rejection showed that patients with anti-HLA dnDSA have significantly higher odds of rejection than patients without anti-HLA (OR = 3.35, 95% CI [2.28-4.91], I2 = 38%).

CONCLUSION:

The results of our meta-analysis show that anti-HLA dnDSA is strongly associated with pancreas graft failure and rejection. Surveillance for anti-HLA dnDSA is an important component of post-transplant immune monitoring.

  • Liu JY
  • Zhang JM
  • Zhan HS
  • Sun LY
  • Wei L
Transpl Int. 2021 Dec;34(12):2483-2493 doi: 10.1111/tri.14107.

The use of Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs) in adoptive immunotherapy in hematopoietic stem cell transplantation (HSCT) patients with post-transplantation lymphoproliferative disorder (PTLD) has demonstrated safety and effectiveness. EBV-CTLs might also be the effective treatment of refractory PTLD of solid organ transplantation (SOT) recipients. Two independent assessors searched Pubmed, Embase, Cochrane Library, and Web of Science from their inception to November 2020. Eleven studies with 76 patients (42, 55% male) were included. We extracted the data and completed the quality assessments. Most of the studies were from Europe and the USA. Liver and kidney transplantation accounted for most of the transplant types. Thirty-five (46.1%) patients were diagnosed with monomorphic PTLD, and B lymphocyte type was the most common. All the patients received primary treatment for PTLD while it was ineffective. CTLs included autologous EBV-CTLs (15/76, 22%) and HLA-matched third-party EBV-CTLs (61/76, 78%). The response rate for EBV-CTL treatment of refractory PTLD was 66%. Of 50 patients, 36 achieved complete remission and 14 achieved partial remission. EBV-DNA level decreased in 39 patients. Adverse reactions were rare and mild. We conclude that adoptive therapy with EBV-specific CTLs is safe, well-tolerated, and effective in PTLD.

  • Permpalung N
  • Kittipibul V
  • Mekraksakit P
  • Rattanawong P
  • Nematollahi S
  • et al.
Transplantation. 2021 Oct 1;105(10):2291-2306 doi: 10.1097/TP.0000000000003576.
BACKGROUND:

There is no consensus guidance on when to reinitiate Pneumocystis jirovecii pneumonia (PJP) prophylaxis in solid organ transplant (SOT) recipients at increased risk. The 2019 American Society of Transplantation Infectious Diseases Community of Practice (AST IDCOP) guidelines suggested to continue or reinstitute PJP prophylaxis in those receiving intensified immunosuppression for graft rejection, cytomegalovirus (CMV) infection, higher dose of corticosteroids, or prolonged neutropenia.

METHODS:

A literature search was conducted evaluating all literature from existence through April 22, 2020, using MEDLINE and EMBASE. (The International Prospective Register of Systematic Reviews registration number: CRD42019134204).

RESULTS:

A total of 30 studies with 413 276 SOT recipients were included. The following factors were associated with PJP development: acute rejection (pooled odds ratio [pOR], 2.35; 95% confidence interval [CI], 1.69-3.26); study heterogeneity index [I2] = 23.4%), CMV-related illnesses (pOR, 3.14; 95% CI, 2.30-4.29; I2 = 48%), absolute lymphocyte count <500 cells/mm3 (pOR, 6.29; 95% CI, 3.56-11.13; I2 = 0%), BK polyomavirus-related diseases (pOR, 2.59; 95% CI, 1.22-5.49; I2 = 0%), HLA mismatch ≥3 (pOR, 1.83; 95% CI, 1.06-3.17; I2 = 0%), rituximab use (pOR, 3.03; 95% CI, 1.82-5.04; I2 = 0%), and polyclonal antibodies use for rejection (pOR, 3.92; 95% CI, 1.87-8.19; I2 = 0%). On the other hand, sex, CMV mismatch, interleukin-2 inhibitors, corticosteroids for rejection, and plasmapheresis were not associated with developing PJP.

CONCLUSIONS:

PJP prophylaxis should be considered in SOT recipients with lymphopenia, BK polyomavirus-related infections, and rituximab exposure in addition to the previously mentioned risk factors in the American Society of Transplantation Infectious Diseases Community of Practice guidelines.

  • Honeyman C
  • Stark HL
  • Fries CA
  • Gorantla VS
  • Davis MR
  • et al.
J Plast Reconstr Aesthet Surg. 2021 Feb;74(2):316-326 doi: 10.1016/j.bjps.2020.08.052.
INTRODUCTION:

A solid organ transplant (SOT) recipient, already taking immunosuppression, may represent the ideal candidate for vascularised composite allograft transplantation (VCA). However, concerns have been raised about the potential risk of SOT loss or the need for increased immunosuppression to sustain the VCA. This systematic review examines all published cases of SOT recipients who have received a VCA to establish associated morbidity and immunosuppression requirements.

METHODS:

A systematic review was performed in accordance with the PRISMA guidelines. The PubMed, MEDLINE and EMBASE databases were searched for original articles published between January 1997 and May 2019. Only articles relating to patients who had received both a VCA and SOT with a reported follow up of greater than six months were included.

RESULTS:

Fifteen articles were identified, including data from 39 VCAs in 37 patients. There was no increase in the number of SOT rejection episodes, complications such as post-transplant lymphoproliferative disorder or graft versus host disease, de novo donor specific HLA antibodies or short-term risks to the recipient when compared with SOT in isolation. One child required a sustained increase in their baseline immunosuppression following bilateral hand transplantation.

CONCLUSIONS:

In this small heterogeneous cohort, the addition of a VCA to a SOT does not appear to increase the short-term risks to the SOT or the patient with comparable results to SOT in isolation. However, data are often poorly reported and longer-term follow up and uniform reporting of outcomes would be beneficial to more accurately assess the safety profile of combining VCA with SOT.

  • Amoroso A
  • Magistroni P
  • Vespasiano F
  • Bella A
  • Bellino S
  • et al.
Transplantation. 2021 Jan 1;105(1):193-200 doi: 10.1097/TP.0000000000003507.
BACKGROUND:

SARS-CoV-2 infection is heterogeneous in clinical presentation and disease evolution. To investigate whether immune response to the virus can be influenced by genetic factors, we compared HLA and AB0 frequencies in organ transplant recipients and waitlisted patients according to presence or absence of SARS-CoV-2 infection.

METHODS:

A retrospective analysis was performed on an Italian cohort composed by transplanted and waitlisted patients in a January 2002 to March 2020 time frame. Data from this cohort were merged with the Italian registry of COVID+ subjects, evaluating infection status of transplanted and waitlisted patients. A total of 56 304 cases were studied with the aim of comparing HLA and AB0 frequencies according to the presence (n = 265, COVID+) or absence (n = 56 039, COVID-) of SARS-CoV-2 infection.

RESULTS:

The cumulative incidence rate of COVID-19 was 0.112% in the Italian population and 0.462% in waitlisted/transplanted patients (OR = 4.2; 95% CI, 3.7-4.7; P < 0.0001). HLA-DRB1*08 was more frequent in COVID+ (9.7% and 5.2%: OR = 1.9, 95% CI, 1.2-3.1; P = 0.003; Pc = 0.036). In COVID+ patients, HLA-DRB1*08 was correlated to mortality (6.9% in living versus 17.5% in deceased: OR = 2.9, 95% CI, 1.15-7.21; P = 0.023). Peptide binding prediction analyses showed that these DRB1*08 alleles were unable to bind any of the viral peptides with high affinity. Finally, blood group A was more frequent in COVID+ (45.5%) than COVID- patients (39.0%; OR = 1.3; 95% CI, 1.02-1.66; P = 0.03).

CONCLUSIONS:

Although preliminary, these results suggest that HLA antigens may influence SARS-CoV-2 infection and clinical evolution of COVID-19 and confirm that blood group A individuals are at greater risk of infection, providing clues on the spread of the disease and indications about infection prognosis and vaccination strategies.

Author details unavailable

ClinicalTrials.gov. 2020.
COVID-19 is a global major public health emergency that disproportionately affects patients with risk factors such as advanced age, heart and lung disease, diabetes, hypertension, as well as compromised immunity. Despite the recent worldwide emergence of this disease and its rapid progression to a pandemic, very little is known about the risks facing solid organ recipients. The study aims to elucidate the prevalence of symptomatic, subclinical, and asymptomatic infection in the transplanted population by assessing their immunological response to SARS-CoV-2 infection. This will be studied seroepidemiologically in the whole cohort and retrospectively in transplanted patients admitted to hospital for COVID-19. Primary objective: to elucidate the cumulative prevalence of SARS-CoV-2 infection in the transplanted population related to symptoms and hospitalizations; to assess the magnitude of immunological response and seroconversion kinetics for COVID-19. Secondary objectives: To examine the influence of medical parameters on COVID-19 infection and immune response such as: age, comorbidities current and recent pharmacological treatment, organ transplanted, and blood type, HLA genotype. Study design: Part 1: Longitudinal cohort study for seroepidemiology and disease burden. Part 2: Retrospective case-series for seroconversion kinetics and clinical course assessment. Study population: All solid organ transplanted patients in the Transplant Institute, Sahlgrenska University hospital, catchment area. https://clinicaltrials.gov/show/NCT04407221
  • Tait BD
  • Süsal C
  • Gebel HM
  • Nickerson PW
  • Zachary AA
  • et al.
Transplantation. 2013 Jan 15;95(1):19-47 doi: 10.1097/TP.0b013e31827a19cc.
Clinical Appraiser: Mr Simon Knight, Centre for Evidence in Transplantation, The Royal College of Surgeons of England.
Methodological Appraisers:
  • Rhiannon Deierhoi Reed, University of Alabama at Birmingham, Comprehensive Transplant Institute, USA
  • Katriona O'Donoghue, Centre for Evidence in Transplantation, The Royal College of Surgeons of England
Overall Guideline Assessment: ★★★★★☆☆ (5 of 7)
Appraiser 1 Appraiser 2 Appraiser 3
4 6 4
Recommendation for future use
Appraiser 1 Appraiser 2 Appraiser 3
Yes with modifications Yes Yes with modifications
Domain 1 - Scope and Purpose 89%
Appraiser 1 Appraiser 2 Appraiser 3
1. The overall objective(s) of the guideline is (are) specifically described 7 6 7
2. The health question(s) covered by the guideline is (are) specifically described 7 6 7
3. The population (patients, public, etc.) to whom the guideline is meant to apply is specifically described 4 6 7
Domain 2 - Stakeholder Involvement 43%
Appraiser 1 Appraiser 2 Appraiser 3
4. The guideline development group includes individuals from all the relevant professional groups 4 7 6
5. The views and preferences of the target population (patients, public, etc.) have been sought 1 1 1
6. The target users of the guideline are clearly defined 2 6 4
Domain 3 - Rigour of Development 35%
Appraiser 1 Appraiser 2 Appraiser 3
7. Systematic methods were used to search for evidence 2 4 1
8. The criteria for selecting the evidence are clearly described 1 2 1
9. The strengths and limitations of the body of evidence are clearly described 5 7 6
10. The methods for formulating the recommendations are clearly described 3 6 4
11. The health benefits, side effects, and risks have been considered in formulating the recommendations 5 2 6
12. There is an explicit link between the recommendations and the supporting evidence 4 7 2
13. The guideline has been externally reviewed by experts prior to its publication 1 1 1
14. A procedure for updating the guideline is provided 1 2 1
Domain 4 - Clarity of Presentation 91%
Appraiser 1 Appraiser 2 Appraiser 3
15. The recommendations are specific and unambiguous 6 6 7
16. The different options for management of the condition or health issue are clearly presented 6 7 6
17. Key recommendations are easily identifiable 6 7 7
Domain 5 - Applicability 22%
Appraiser 1 Appraiser 2 Appraiser 3
18. The guideline describes facilitators and barriers to its application 2 3 4
19. The guideline provides advice and/or tools on how the recommendations can be put into practice 1 2 4
20. The potential resource implications of applying the recommendations have been considered 1 1 1
21. The guideline presents monitoring and/ or auditing 4 4 1
Domain 6 - Editorial Independence 89%
Appraiser 1 Appraiser 2 Appraiser 3
22. The views of the funding body have not influenced the content of the guideline 4 7 7
23. Competing interests of guideline development group members have been recorded and addressed 6 7 7
BACKGROUND:

The introduction of solid-phase immunoassay (SPI) technology for the detection and characterization of human leukocyte antigen (HLA) antibodies in transplantation while providing greater sensitivity than was obtainable by complement-dependent lymphocytotoxicity (CDC) assays has resulted in a new paradigm with respect to the interpretation of donor-specific antibodies (DSA). Although the SPI assay performed on the Luminex instrument (hereafter referred to as the Luminex assay), in particular, has permitted the detection of antibodies not detectable by CDC, the clinical significance of these antibodies is incompletely understood. Nevertheless, the detection of these antibodies has led to changes in the clinical management of sensitized patients. In addition, SPI testing raises technical issues that require resolution and careful consideration when interpreting antibody results.

METHODS:

With this background, The Transplantation Society convened a group of laboratory and clinical experts in the field of transplantation to prepare a consensus report and make recommendations on the use of this new technology based on both published evidence and expert opinion. Three working groups were formed to address (a) the technical issues with respect to the use of this technology, (b) the interpretation of pretransplantation antibody testing in the context of various clinical settings and organ transplant types (kidney, heart, lung, liver, pancreas, intestinal, and islet cells), and (c) the application of antibody testing in the posttransplantation setting. The three groups were established in November 2011 and convened for a "Consensus Conference on Antibodies in Transplantation" in Rome, Italy, in May 2012. The deliberations of the three groups meeting independently and then together are the bases for this report.

RESULTS:

A comprehensive list of recommendations was prepared by each group. A summary of the key recommendations follows. Technical Group: (a) SPI must be used for the detection of pretransplantation HLA antibodies in solid organ transplant recipients and, in particular, the use of the single-antigen bead assay to detect antibodies to HLA loci, such as Cw, DQA, DPA, and DPB, which are not readily detected by other methods. (b) The use of SPI for antibody detection should be supplemented with cell-based assays to examine the correlations between the two types of assays and to establish the likelihood of a positive crossmatch (XM). (c) There must be an awareness of the technical factors that can influence the results and their clinical interpretation when using the Luminex bead technology, such as variation in antigen density and the presence of denatured antigen on the beads. Pretransplantation Group: (a) Risk categories should be established based on the antibody and the XM results obtained. (b) DSA detected by CDC and a positive XM should be avoided due to their strong association with antibody-mediated rejection and graft loss. (c) A renal transplantation can be performed in the absence of a prospective XM if single-antigen bead screening for antibodies to all class I and II HLA loci is negative. This decision, however, needs to be taken in agreement with local clinical programs and the relevant regulatory bodies. (d) The presence of DSA HLA antibodies should be avoided in heart and lung transplantation and considered a risk factor for liver, intestinal, and islet cell transplantation. Posttransplantation Group: (a) High-risk patients (i.e., desensitized or DSA positive/XM negative) should be monitored by measurement of DSA and protocol biopsies in the first 3 months after transplantation. (b) Intermediate-risk patients (history of DSA but currently negative) should be monitored for DSA within the first month. If DSA is present, a biopsy should be performed. (c) Low-risk patients (nonsensitized first transplantation) should be screened for DSA at least once 3 to 12 months after transplantation. If DSA is detected, a biopsy should be performed. In all three categories, the recommendations for subsequent treatment are based on the biopsy results.

CONCLUSIONS:

A comprehensive list of recommendations is provided covering the technical and pretransplantation and posttransplantation monitoring of HLA antibodies in solid organ transplantation. The recommendations are intended to provide state-of-the-art guidance in the use and clinical application of recently developed methods for HLA antibody detection when used in conjunction with traditional methods.

  • Howell WM
  • Harmer A
  • Briggs D
  • Dyer P
  • Fuggle SV
  • et al.
Int J Immunogenet. 2010 Dec;37(6):435-7 doi: 10.1111/j.1744-313X.2010.00955.x.

Ongoing technological developments in antibody detection and characterisation allowing relative quantitation of HLA-specific antibody levels, combined with crossmatch results, now allow a graded assessment of patient potential donor immunological risk for allotransplantation, rather than a simple 'positive' or 'negative' categorization of crossmatch results. These developments have driven a thorough revision of the British Society for Histocompatibility & Immunogenetics and British Transplantation Society Guidelines for the Detection and Characterisation of Clinically Relevant Antibodies in Allotransplantation. These newly published revised Guidelines contain a number of recommendations as to best practice for antibody detection and crossmatching for the transplantation of a wide range of solid organs and tissues. These recommendations are briefly summarized in this article.