Implementing community-based Dried Blood Spot (DBS) testing for HIV and hepatitis C: a qualitative analysis of key facilitators and ongoing challenges.

BACKGROUND: In 2018, the Community-Based Research Centre (CBRC) invited gay, bisexual, trans, queer men and Two-Spirit and non-binary people (GBT2Q) at Pride Festivals across Canada to complete in-person Sex Now surveys and provide optional dried blood spot (DBS) samples screening for human immunodeficiency virus (HIV) and hepatitis C virus (HCV). As there is a lack of research evaluating the implementation of DBS sampling for GBT2Q in community settings, we aimed to evaluate this intervention, identifying key facilitators and ongoing challenges to implementing community-based DBS screening for HIV/HCV among GBT2Q. METHODS: We conducted sixteen one-on-one interviews with individuals involved with the community-based DBS collection protocol, including research staff, site coordinators, and volunteer DBS collectors. Most individuals involved with DBS collection were "peers" (GBT2Q-identified). The Consolidated Framework for Implementation Research (CFIR) guided our data collection and analysis. RESULTS: Interviewees felt that DBS collection was a low-barrier, cost-effective, and simple way for peers to quickly screen a large number of Sex Now respondents. Interviewees also noted that the community and peer-based aspects of the research helped drive recruitment of Sex Now respondents. Most interviewees felt that the provision of results took too long, and that some Sex Now respondents would have preferred to receive their test results immediately (e.g., rapid or point-of-care testing). CONCLUSION: Peer-based DBS sampling can be an effective and relatively simple way to screen GBT2Q at Pride Festivals for more than one sexually transmitted and blood borne infection.

Dynamic Behaviour of Donor Specific Antibodies in the Early Period Following HLA Incompatible Kidney Transplantation.

In HLA-incompatible kidney transplantation, monitoring donor-specific antibodies (DSA) plays a crucial role in providing appropriate treatment and increases kidney survival times. This work aimed to determine if early post-transplant DSA dynamics inform graft outcome over and above other predictive factors. Eighty-eight cases were classified by unsupervised machine learning into five distinct DSA response groups: no response, fast modulation, slow modulation, rise to sustained and sustained. Fast modulation dynamics gave an 80% rate for early acute rejection, whereas the sustained group was associated with the lowest rejection rates (19%). In complete contrast, the five-year graft failure was lowest in the modulation groups (4-7%) and highest in the sustained groups (25-31%). Multivariable analysis showed that a higher pre-treatment DSA level, male gender and absence of early acute rejection were strongly associated with a sustained DSA response. The modulation group had excellent five-year outcomes despite higher rates of early rejection episodes. This work further develops an understanding of post-transplant DSA dynamics and their influence on graft survival following HLA-incompatible kidney transplantation.

Gay, bisexual, and other men who have sex with men accessing STI clinics: Optimizing HIV PrEP implementation.

BACKGROUND: Gay, bisexual and other men who have sex with men (gbMSM) who attend STI clinics represent an easily accessible population for promoting HIV prevention interventions. We examined characteristics of gbMSM STI clinic attendees to identify those who could most benefit from pre-exposure prophylaxis (PrEP). SETTING: GbMSM STI clinic attendees in British Columbia (BC), Canada. METHODS: A clinical electronic charting system of STI clinics in BC was used to identify gbMSM from 2004 to 2017. Incident HIV cases were defined as testers who had at least one HIV-negative test and a subsequent HIV-positive test. Seroconversion rates were calculated by risk factor variables and by year. Cox proportional hazards regression was used to identify independent predictors of HIV seroconversion. RESULTS: There were 9,038 gbMSM included, of whom 257 HIV seroconverted over the study period and 8,781 remained negative HIV testers, contributing 650.8 and 29,591.0 person-years to the analysis, respectively. The overall rate of seroconversion was 0.85 per 100 person-years (95% CI: 0.75-0.96). Incidence rates were higher among patients reporting >5 partners in the previous six months, inconsistent condom use, or having a partner living with HIV and who had a previous or concurrent diagnosis of rectal gonorrhea or rectal chlamydia. gbMSM presenting with two STIs such as rectal gonorrhea and syphilis (3.59/100 person-years [95%CI: 2.33-5.22]) or rectal chlamydia and syphilis (3.01/100 person-years [95%CI: 2.00-4.29]) had the highest incidence rates. CONCLUSION: gbMSM with preceding or concurrent rectal STI diagnoses or syphilis had higher rates of HIV seroconversion. The data support the inclusion of specific STI diagnoses as an indication for PrEP.

Who knows about U = U? Social positionality and knowledge about the (un)transmissibility of HIV from people with undetectable viral loads.

"U = U" is the principle that HIV is untransmittable from people living with an undetectable HIV viral-load. Wide-spread knowledge about U = U is believed to produce public health benefit by reducing HIV-related stigma - promoting wellbeing for people living with HIV. Therefore, we examined the diffusion of U = U with respect to the social position of sexual and gender minority men (SGMM). Participants were SGMM recruited from 16 LGBTQ2S+ pride festivals across Canada. Social position was measured using an index assessing whether participants were (a) trans, (b) a person of colour, (c) Indigenous, (d) born abroad, (e) bisexual or straight, (f) not out, (g) struggling with money, (h) not college educated, (i) and not participating in LGBTQ2S+ Organizations, Queer Pop-ups, or HIV advocacy organizations. Multivariable logistic regression tested whether Index Scores were associated with knowledge about U = U. Among 2681 participants, 72.6% knew about U = U. For HIV-negative/unknown status SGMM, each 1-point increase in Social Positionality Index Scores was associated with a 21% reduction in the odds that they knew about U = U (aOR: 0.79 [0.73, 0.85], per 1-point increase). Results indicate that social marginalization harms the diffusion of HIV-related biomedical knowledge, independent of risk-taking behaviour and other factors.

Democratizing Access to Community-Based Survey Findings Through Dynamic Data Visualizations.

OurStats ( https://www.cbrc.net/ourstats ) is a data visualization dashboard developed by the Community-Based Research Centre (CBRC) to increase access to data from the Sex Now surveys-Canada's largest community-based surveillance study of gay and bisexual men. An evaluation of the OurStats dashboard was conducted using an online survey distributed through the CBRC and Advance Alliance-an alliance of Canada's leading HIV and queer men's health organizations. Since being launched in November 2019 (through December 2019), 350 unique visitors used the OurStats Dashboard (5.8 per day). Based on responses from 10 community partners, all respondents said they would probably/definitely use OurStats again and would probably/definitely recommend it to colleagues; nine felt it was much/somewhat better than traditional academic outputs (e.g., poster presentations, journal articles); and seven felt it was much/somewhat better than traditional knowledge translation outputs (e.g., fliers, posters, and social media posts). Respondents said they would use OurStats to identify needs of gay and bisexual men (n = 9), prepare grant/funding applications (n = 9), prepare presentations about Sex Now data (n = 7), and evaluate the impact of local programs (n = 4). Overall, half felt that OurStats was somewhat/extremely easy to use and half felt that it was somewhat difficult to use. The most commonly identified requested improvement was to provide help documentation that explained how each of the display settings changed the visualizations. From these findings, we conclude that dynamic visualizations for community-based survey data are highly feasible and acceptable, provided appropriate support is available to help community partners use these tools.

Clinical Relevance of Donor-Specific IgM Antibodies in HLA Incompatible Renal Transplantation: A Retrospective Single-Center Study.

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). IgM was defined positive if the mean fluorescence values were greater than 2000. Presence of pre- and post-transplant IgM was correlated with early antibody mediated rejection episodes (within 30 days post-transplantation) and graft failure. Statistical analyses were performed using SPSS IBM software. Graft survival estimates were death-censored. The presence of pre-transplant IgM DSA did not predict rejection (p=0.83) or graft failure (p=0.424). The post-transplant IgM DSA levels peaked at day 14 (similar to IgG DSA levels). Presence of IgM DSA post-transplant (de novo and resynthesis) was not associated with rejection (p=0.83). However, post-transplant IgM was associated with graft failure (p=0.037). This study shows additional testing of post-transplant IgM DSA over and above IgG is important as post-transplant IgM DSA is associated with graft failure.

Pregnancy-induced HLA antibodies respond more vigorously after renal transplantation than antibodies induced by prior transplantation.

Acute antibody mediated rejection after HLA-specific antibody incompatible renal transplantation is related to donor specific HLA antibody (DSA) levels. DSA levels may rise sharply after transplant, and aim of this study was to examine changes in DSA levels, particularly according to the primary sensitising event. Changes in 220 HLA specificities in 64 patients over the first 30days after transplantation were evaluated using microbead assays. The greatest increase from pre-treatment to peak DSA levels was seen in pregnancy-stimulated specificities, median (IQR) increase in MFI of 1981 (94-5870). The next highest increase was for those sensitised by transplant with repeat HLA epitope mismatch, at 546 (-308-2698) (p<0.01). The difference was especially marked when the pre-treatment antibody level was low; with pre-treatment MFI <1000, peak level was >1000 in 19/26 (73%) of pregnancy stimulated specificities, compared with 9/29 (31%) for all others (p<0.001). DSA production to specificities stimulated by previous pregnancy was marked, even from very low pre-transplant levels. By contrast, there was a lower rate of antibody resynthesis to specificities repeated from previous transplants, both at antigen and epitope levels.

Antibody-incompatible kidney transplantation in 2015 and beyond.

Rejection caused by donor-specific antibodies (principally ABO and HLA antibodies) has become one of the major barriers to successful long-term transplantation. This review focuses on clinical outcomes in antibody-incompatible transplantation, the current state of the science underpinning clinical observations, and how these may be translated into further novel therapies. The clinical outcomes for allografts facing donor-specific antibodies are at present determined largely by the use of agents developed in the 20th century for the treatment of T-lymphocyte-mediated cellular rejection, such as interleukin-2 agents and anti-thymocyte globulin. These treatments are partially effective, because acute antibody-mediated rejection is mediated to a considerable extent by T lymphocytes. However these treatments are essentially ineffective in chronic antibody-mediated rejection. Future therapies for the prevention and treatment of antibody-mediated rejection are likely to fall into the categories of those that reduce antibody production, extracorporeal antibody removal and disruption of the effector arms of antibody-mediated tissue damage.

Profiling antibodies to class II HLA in transplant patient sera.

Immunizing events including pregnancy, transfusions, and transplantation promote strong alloantibody responses to HLA. Such alloantibodies to HLA preclude organ transplantation, foster hyperacute rejection, and contribute to chronic transplant failure. Diagnostic antibody-screening assays detect alloreactive antibodies, yet key attributes including antibody concentration and isotype remain largely unexplored. The goal here was to provide a detailed profile of allogeneic antibodies to class II HLA. Methodologically, alloantibodies were purified from sensitized patient sera using an HLA-DR11 immunoaffinity column and subsequently categorized. Antibodies to DR11 were found to fix complement, exist at a median serum concentration of 2.3µg/mL, consist of all isotypes, and isotypes IgG2, IgM, and IgE were elevated. Because multimeric isotypes can confound diagnostic determinations of antibody concentration, IgM and IgA isotypes were removed and DR11-IgG tested alone. Despite removal of multimeric isotypes, patient-to-patient antibody concentrations did not correlate with MFI values. In conclusion, allogeneic antibody responses to DR11 are comprised of all antibody isotypes at differing proportions, these combined isotypes fix complement at nominal serum concentrations, and enhancements other than the removal of IgM and IgA multimeric isotypes may be required if MFI is to be used as a means of determining anti-HLA serum antibody concentrations in diagnostic clinical assays.

Elevated pretransplantation soluble BAFF is associated with an increased risk of acute antibody-mediated rejection.

BACKGROUND: B cells play an important role in renal allograft pathology, particularly in acute and chronic antibody-mediated rejection (AMR). B-cell activating factor belonging to the tumor necrosis factor family (BAFF; also known as BLyS) is a cytokine that enhances B-cell survival and proliferation. METHODS: We analyzed serum BAFF levels in 32 patients undergoing antibody-incompatible (Ai) renal transplantation and 319 antibody-compatible transplant recipients and sought to determine whether there was a correlation with acute rejection and with transplant function and survival. RESULTS: We demonstrate that, in patients undergoing Ai transplantation, elevated serum BAFF levels at baseline (before both antibody removal/desensitization and transplantation) are associated with an increased risk of subsequent AMR. In antibody-compatible transplant recipients at lower risk of AMR, no statistically significant association was observed between pretransplantation serum BAFF and AMR. CONCLUSIONS: These data raise the possibility that, in high immunologic risk patients undergoing Ai transplantation, the presence of elevated pretransplantation serum BAFF might identify those at increased risk of AMR. BAFF neutralization may be an interesting therapeutic strategy to explore in these patients, particularly because such agents are available and have already been used in the treatment of autoimmunity.

Rapid resolution of severe sustained low blood pressure in haemodialysis patients after successful renal transplantation.

BACKGROUND: Low blood pressure occurring in the absence of volume depletion, anti-hypertensive medication, heart failure or cortisol deficiency occurs in ~5-10% of haemodialysis patients, and can result in serious complications. The pathophysiology of this syndrome is poorly understood. METHODS: We describe eight cases with dialysis-associated hypotension who underwent renal transplantation. Four patients were severely hypotensive with a systolic blood pressure (SBP) <100 mmHg before and during dialysis, and four had a SBP usually <100 mmHg during dialysis, but usually >100 mmHg between sessions. All had donor-specific human leukocyte antigen antibodies. Six patients underwent pre-transplant plasmapheresis, which was curtailed in two because of further falls in blood pressure. Two patients experienced clotting of their arteriovenous fistula. In one patient cryofiltration was used, which was tolerated without severe falls in the BP. The remaining patient, who had hypotension-associated retinal vein thrombosis before transplant, was supported with an epinephrine infusion and did not receive plasmapheresis. RESULTS: Post-transplant, the first patient did not receive pressor therapy and died from bowel ischaemia. The other seven patients were supported with inotropes on critical care. The administration of steroids did not reverse hypotension. The mean pre-treatment SBP was 96 mmHg (range 71-110, SEM 5.0). After inotropes were withdrawn and graft function was established, the mean SBP was 127 mmHg (range 113-149, SEM 4.9) (P < 0.01). CONCLUSIONS: Renal transplantation was performed successfully and safely in patients when pressor therapy was used to treat severe dialysis-associated hypotension and, moreover, the blood pressure normalized rapidly after graft function was established.

Cryofiltration in the treatment of cryoglobulinemia and HLA antibody-incompatible transplantation.

Cryofiltration is a technique in which plasma is separated from blood and chilled, leading to the formation of "cryogel", a composite of heparin, fibronectin, fibrinogen, immunoglobulins, and other proteins. This is retained by further filtration and plasma is returned to the patient. There may be a role for cryofiltration in the treatment of cryoglobulinemia or where the application of other forms of plasmapheresis or immunoadsorption is limited. Five patients received six courses of cryofiltration. Two patients had cryoglobulinemia and three were treated before HLA antibody-incompatible renal transplantation. The treatment was associated with few adverse effects, and it was possible to treat up to 120 mL/kg plasma per session. There was a good clinical response in four patients. One patient was switched back to double filtration plasmapheresis (DFPP) because cryofiltration seemed to remove HLA antibodies less effectively, but the other two transplants have excellent function. In the cryoglobulinemia patients there was excellent clearance of cryoglobulins during each treatment (mean decrease of 78.2 (SD 14.1)% per treatment). Compared with DFPP, fewer immunoglobulins were removed and the mean percentage reductions in immunoglobulin G per treatment were 36.0 (4.0)% for cryoglobulinemia and 59.2 (2.5)% for DFPP (P < 0.01), with respective mean plasma volumes of 64.2 (10.3) and 71.1 (6.8) mL/kg treated. Cryofiltration offers a treatment choice in patients with cryoglobulinemia and in those who may not be able to tolerate high-volume DFPP. The technique used in the patients described here was less effective than DFPP; however, use of an alternative fractionator and treatment of higher plasma volumes may enhance the efficiency of cryofiltration.

Double filtration plasmapheresis in antibody-incompatible kidney transplantation.

Double filtration plasmapheresis (DFPP) was used in preference to plasma exchange in our program of antibody-incompatible transplantation, to treat higher volumes of plasma. Forty-two patients had 259 sessions of DFPP, 201 pre-transplant and 58 post-transplant. At the first treatment session, the mean plasma volume treated was 3.81 L (range 3-6 L), 55.5 mL/kg (range 36.2-83.6 mL/kg). Serum IgG fell by mean 59.4% (SD 10.2%), and IgM by 69.3% (SD 16.1%). Nine patients did not require increases in plasma volumes treated, and six did not tolerate higher plasma volumes. In the remaining patients, the mean maximum plasma volume treated pre-transplant was 6.67 L (range 4-15 L), 96.1 mL/kg (range 60.2-208.9 mL/kg). The complement dependent cytotoxic crossmatch was positive in 14 cases pre-treatment, and remained positive in six (42.8%) cases. The flow cytometric crossmatch was positive in 29 cases pre-treatment, and in 21 (72.4%) after DFPP. Post-transplant, DFPP was ineffective at reducing donor specific antibody levels during periods of rapid donor specific antibody synthesis. Post-transplant, the one year graft survival rate was 94%, although there was a high rate of early rejection. In summary, DFPP enabled the treatment of plasma volumes that were almost double those that would have been feasible with plasma exchange. Despite this, most patients were transplanted with a positive crossmatch, and DFPP post-transplant was unable to control rising antibody levels.

Soluble CD30 and Cd27 levels in patients undergoing HLA antibody-incompatible renal transplantation.

HLA antibody-incompatible transplantation has a higher risk of rejection when compared to standard renal transplantation. Soluble CD30 (sCD30) has been shown in many, but not all, studies to be a biomarker for risk of rejection in standard renal transplant recipients. We sought to define the value of sCD30 and soluble CD27 (sCD27) in patients receiving HLA antibody-incompatible transplants. Serum taken at different time points from 32 HLA antibody-incompatible transplant recipients was retrospectively assessed for sCD30 and sCD27 levels by enzyme-linked immunosorbent assay (ELISA). This was compared to episodes of acute rejection, post-transplant donor-specific antibody (DSA) levels and 12 month serum creatinine levels. No association was found between sCD27 and sCD30 levels and risk of acute rejection or DSA levels. Higher sCD30 levels at 4-6 weeks post-transplantation were associated with a higher serum creatinine at 12 months. Conclusion patients undergoing HLA antibody-incompatible transplantation are at a high risk of rejection but neither sCD30 (unlike in standard transplantation) nor sCD27 was found to be a risk factor. High sCD30 levels measured at 4-6 weeks post-transplantation was associated with poorer graft function at one year.

The histological development of acute antibody-mediated rejection in HLA antibody-incompatible renal transplantation.

BACKGROUND: The aim of this study was to examine the development of acute antibody-mediated rejection in HLA antibody-incompatible renal transplantation in relation to the Banff 07 histological classification. METHODS: Renal biopsies were scored using the Banff 07 diagnostic criteria, and paraffin-embedded sections were stained with the pan-leucocyte marker CD45. RESULTS: Thirty-six patients had 72 renal biopsies. In biopsies performed 30 min after graft reperfusion, the mean number of CD45+ cells per glomerulus was higher than in control grafts (P < 0.04) and was associated with the donor-specific antibody (DSA) level at transplantation measured by microbeads (P < 0.01), and eight out of nine patients with greater than five CD45+ cells per glomerulus had early post-transplant rejection or oliguria, compared to 11 out of 20 with less than five cells per glomerulus (P < 0.01). In the first 10 days post-transplant, although peritubular capillary (PTC) leucocyte margination grade 3 and C4d deposition were specific for rejection, their sensitivities were low. PTC C4d staining was only seen in two out of 11 biopsies taken in the first 5 days after transplant, even in the presence of rejection, but was present in the majority of later biopsies with rejection. In biopsies stained for CD3, CD68 and CD20, it was notable that CD20+ cells were not seen during acute rejection, the infiltrates comprising CD3+ and CD68+ leucocytes. CONCLUSIONS: Glomerular margination of leucocytes occurred early after transplantation and was associated with DSA level and early graft dysfunction. The Banff 07 PTC margination scoring system was easy to apply, especially when CD45 staining was used, and PTC margination grade 3 was always associated with clinical rejection.

Survival and transplantation in end-stage renal disease: a prospective study of a multiethnic population.

INTRODUCTION: Accurate assessment of determinants of patient survival in end-stage renal disease is important for counselling, clinical management and resource planning. To address this we have analysed survival and risk factors for survival for patients treated for end-stage renal disease in a multi-ethnic UK population. METHODS: A multicentre prospective observational cohort study was performed in four teaching hospital renal units serving a total population of four million people. A total of 884 consecutive patients treated with renal replacement therapy were studied. Cox proportional hazard modelling and adjusted survival curves were used to assess the impact of a range of variables on patients surviving dialysis for more than 90 days. Further analysis was undertaken to determine the likelihood of transplantation in different ethnic groups. RESULTS: Survival was 29% after a mean and median follow up of 4.6 and 4.2 years, respectively. Factors associated with worse survival included the following: age; for each decade of life the relative risk (RR) of death was 1.52 (95% confidence intervals 1.41-1.65, p < 0.0001); comorbidity, one or two comorbid conditions, RR = 1.56 (95% CI 1.24-1.95, p < 0.001) and three or more comorbid conditions, RR = 2.34 (1.68-3.27, p < 0.001). Factors associated with better survival included the following: south-Asian ethnicity, RR = 0.6 (0.46-0.80, p < 0.001); renal transplantation, RR = 0.20 (95% CI 0.11-0.59, p < 0.0001) and glomerulonephritis as the primary renal disease, RR = 0.70 (0.50-0.97, p = 0.04). Factors associated with likelihood of transplantion were having a functioning fistula/peritoneal dialysis catheter at start of dialysis (RR 1.91, 95% CI 1.24-2.94, p = 0.003) and glomerulonephritis (RR 9.54, 95% CI 2.43-37.64, p = 0.001). Patients were less likely to receive if they were black (RR 0.10, 95% CI 0.02-0.34, p < 0.001), South Asian (RR 0.64, 95% CI 0.42-0.97, p = 0.037), diabetic (RR 0.06, 95% CI 0.01-0.23, p < 0.001) and had one or two comorbid conditions (RR 0.51, 95% CI 0.32-0.82, p = 0.06). Every decade increase in age was also associated with a lesser likelihood of transplantation (RR 0.55, 95% CI 0.49-0.61, p < 0.001). Discussion. Risk stratification at commencement of chronic dialysis may predict long-term survival in different patient groups. As expected ethnic minorities are less likely to receive a transplant and this should be addressed by the new waiting list prioritization. The better survival on dialysis in this population of patients with south-Asian ethnicity is unexplained and this requires further investigation.

Rises and falls in donor-specific and third-party HLA antibody levels after antibody incompatible transplantation.

BACKGROUND: After human leukocyte antigen (HLA) antibody-incompatible transplantation, donor specific and third party HLA antibodies may be found, and their levels fall in a donor-specific manner during the first month. However, these changes have not been previously described in detail. METHODS: Donor-specific HLA antibody (DSA) and third-party HLA antibody (TPA) levels were measured using the microbead method in 44 presensitized patients who had renal transplantation. RESULTS: DSA+TPA fell in the first 4 days after transplantation, and greater falls in DSA indicated absorption by the graft. This occurred for class I (57.8% fall compared with 20.2% for TPA, P<0.0005), HLA DR (63.0% vs. 24.3%, P<0.0004), and for HLA DP/DQ/DRB3-4 (34% vs. 17.5%, P=0.014). Peak DSA levels occurred at a mean of 13 days posttransplant, and they were higher than pretreatment in 25 (57%) patients and lower in 19 (43%) patients (P=ns). The risk of rejection was associated with peak DSA levels; 15 of 25 (60%) patients with DSA at median fluorescence intensity (MFI) more than 7000U experienced rejection, compared with 4 of 7 (57%) patients with peak DSA MFI 2000 to 7000U, and 2 of 12 (17%) patients with peak DSA MFI less than 2000U (P<0.02). DSA levels subsequently fell in a donor specific manner compared to TPA. CONCLUSION: DSA levels may change markedly in the first month after antibody incompatible transplantation, and the risk of rejection was associated with higher pretreatment and peak levels.

New choices for patients needing kidney transplantation across antibody barriers.

Antibodies in the blood of a kidney transplant recipient can provide a barrier to transplantation, which is additional to the usual possibility of cellular rejection. The antibodies most frequently encountered are ABO (blood group) and human leucocyte antigen (HLA) (tissue-type) antibodies. About 250 living donor transplants each year in the United Kingdom have been stopped because of an antibody barrier. It is now possible to offer a choice of treatment modalities to these people, including exchange transplantation and antibody-incompatible transplantation. It is likely that both schemes will complement each other and both are available in the United Kingdom.

Blood levels of donor-specific human leukocyte antigen antibodies after renal transplantation: resolution of rejection in the presence of circulating donor-specific antibody.

BACKGROUND: Accommodation to antibody is an important mechanism in successful ABO-incompatible transplantation, but its importance in human leukocyte antigen (HLA) antibody-incompatible transplantation is less clear, as sensitive techniques facilitating daily measurement of donor-specific HLA antibodies (DSAs) have only recently been developed. METHODS: We report 24 patients who had HLA antibody-incompatible kidney transplantation (21 living donors, 3 deceased), 21 of whom had pretransplant plasmapheresis. Eight had positive complement-dependent cytotoxic (CDC) crossmatch (XM) pretransplant plasmapheresis, nine had positive flow cytometric (FC) XM, and seven had DSA detectable by microbead analysis only. After transplant, DSA levels were monitored closely with microbead assays. RESULTS: Rejection occurred in five of eight (62.5%) CDC-positive cases, in three of nine (33%) FC-positive cases, and in two of seven (29%) of microbead-only cases at a median of 6.5 days after transplantation. Resolution occurred at a median of 15 days after transplantation, in 8 of 10 cases when the microbead level of DSA had median fluorescence intensity (MFI) >2000 U, in 6 of 10 when the microbead MFI >4000 U. In 8 of 10 cases, the microbead MFI at the time of resolution was greater than at the onset. DSA did not always cause clinical rejection. In five cases with a posttransplant DSA peaking at MFI >2000 U on microbead assay, rejection did not occur. CONCLUSION: These data suggest that the dominant method of successful transplantation was function of the transplant in the presence of circulating DSA, and they also define the period during which this occurred.