Antilymphocyte Antibodies Research Articles

Therapeutic sequencing in inflammatory bowel disease: Determining the optimal position of vedolizumab for long-term Crohn's disease control using real-world evidence.

Several biologics are available for the treatment of moderate to severe Crohn's disease, but data to optimize their use are scarce. Vedolizumab (VDZ) is a gut-selective anti-lymphocyte trafficking monoclonal antibody that was approved in 2014 for the treatment of moderate to severe Crohn's disease. Based on real-world evidence, a model was developed to examine the effect of VDZ's position in the treatment sequence on clinical outcomes. The aim of this study was to develop a model using real-world data to investigate how the positioning of VDZ in a sequence of biologic therapies for CD affects clinical effectiveness outcomes of quality-adjusted life-years (QALYS), patient-reported disease activity, and surgery rates. A semi-Markov sequential model was developed to identify the optimal position of VDZ in a treatment sequence that included corticosteroids (CS), two biologics, and best supportive care (BSC). Using real-world data, three sequences were compared: VDZ as first (position), second, and last biologic (with anti-tumor necrosis factor alpha agents adalimumab (ADA) and infliximab (IFX) and the anti-interleukin-12 and -23 agent ustekinumab (UST) as alternative biologic treatments). Published real-world evidence informed model inputs. Vedolizumab sequences were compared and ranked based on QALYS, patient-reported outcomes from Crohn's disease activity index scores, or proportion of patients undergoing surgery by the 10-year time horizon for model simulation. Sensitivity analyses were used to evaluate the impact of model input uncertainty. Vedolizumab as the first biologic was the optimal position for this treatment according to all criteria, including yielding the highest QALYs (5.09) versus VDZ in second (4.97) and third (4.96) biologic sequence positions in sequences containing CS, anti-TNFα (aggregated data), UST, and BSC; 1780/2000 (89%) probabilistic simulations. In sequences containing ADA, VDZ, and UST biologics, ADA and VDZ in the first-line biologic position yielded QALYs of 5.09 versus 5.07, respectively. Adalimumab as the first biologic was best for clinical remission. This simulation model using real-world evidence indicates that positioning VDZ or ADA as the first biologic is likely to lead to improved long-term patient outcomes when compared to administering these treatments later or starting with IFX monotherapy.

Prevalence of anti-lymphocyte IgM autoantibodies driving complement activation in COVID-19 patients.

COVID-19 patients can develop autoantibodies against a variety of secreted and membrane proteins, including some expressed on lymphocytes. However, it is unclear what proportion of patients might develop anti-lymphocyte antibodies (ALAb) and what functional relevance they might have. We evaluated the presence and lytic function of ALAb in the sera of a cohort of 85 COVID-19 patients (68 unvaccinated and 17 vaccinated) assigned to mild (N=63), or moderate/severe disease (N=22) groups. Thirty-seven patients were followed-up after recovery. We also analyzed in vivo complement deposition on COVID-19 patients' lymphocytes and examined its correlation with lymphocyte numbers during acute disease. Compared with healthy donors (HD), patients had an increased prevalence of IgM ALAb, which was significantly higher in moderate/severe disease patients and persisted after recovery. Sera from IgM ALAb+ patients exhibited complement-dependent cytotoxicity (CDC) against HD lymphocytes. Complement protein C3b deposition on patients' CD4 T cells was inversely correlated with CD4 T cell numbers. This correlation was stronger in moderate/severe disease patients. IgM ALAb and complement activation against lymphocytes may contribute to the acute lymphopenia observed in COVID-19 patients.

Effectiveness and safety of vedolizumab induction with or without budesonide in patients with moderately to severely active Crohn’s disease in Europe: a retrospective observational study

BackgroundVedolizumab (VDZ), a gut-selective anti-lymphocyte trafficking integrin antibody, is effective in treating patients with moderately to severely active Crohn’s disease (CD). In this study, we examined the real-world effectiveness and safety of induction therapy using VDZ alone or in combination with budesonide (VDZ + BUD) among patients with CD in Belgium, Israel, and Switzerland.MethodsThis retrospective chart review analysis included adult patients with moderately to severely active CD who started induction treatment with VDZ or VDZ + BUD (January 2015 through January 2019). The primary objective of this study was to assess the effectiveness in terms of clinical remission of VDZ alone or VDZ + BUD using patient-reported outcomes (PRO) of abdominal pain (AP) and/or loose stool frequency (LSF) (PRO-2) at weeks 0, 2, 6, 10, and 14. Regression models were used to assess differences and associations between the treatment groups.ResultsOverall, 123 patients were included (VDZ, n = 73; VDZ + BUD, n = 50). Clinical remission rates at week 14 were 71.4% (50/70) and 68.0% (34/50) with VDZ and VDZ + BUD, respectively. Mean percentage change in AP and LSF from baseline to week 14 was comparable between the groups. Median (95% confidence interval [CI]) time to clinical remission was 91 [70.0–98.0] and 95 [70.0–98.0] days, respectively. One patient in each group discontinued VDZ and 68.0% of patients in the VDZ + BUD group discontinued BUD before week 14. The rates of overall adverse events were similar between the groups (VDZ, 23.3%; VDZ + BUD, 26.0%).ConclusionsIn this retrospective study, VDZ alone and VDZ + BUD showed similar high remission rates in patients with moderately to severely active CD. Prospective randomized studies are needed to conclude on the role of combining VDZ with BUD.Trial registrationNot applicable.

Induction immunosuppression and post-transplant diabetes mellitus: a propensity-matched cohort study.

Post-transplant diabetes mellitus (PTDM) is a common complication among cardiac transplant recipients, causing diabetes-related complications and death. While certain maintenance immunosuppressive drugs increase PTDM risk, it is unclear whether induction immunosuppression can do the same. Therefore, we evaluated whether induction immunosuppression with IL-2 receptor antagonists, polyclonal anti-lymphocyte antibodies, or Alemtuzumab given in the peri-transplant period is associated with PTDM. We used the Scientific Registry of Transplant Recipients database to conduct a cohort study of US adults who received cardiac transplants between January 2008-December 2018. We excluded patients with prior or multiple organ transplants and those with a history of diabetes, resulting in 17,142 recipients. We created propensity-matched cohorts (n=7,412) using predictors of induction immunosuppression and examined the association between post-transplant diabetes and induction immunosuppression by estimating hazard ratios using Cox proportional-hazards models. In the propensity-matched cohort, the average age was 52.5 (SD=13.2) years, 28.7% were female and 3,706 received induction immunosuppression. There were 867 incident cases of PTDM during 26,710 person-years of follow-up (32.5 cases/1,000 person-years). There was no association between induction immunosuppression and post-transplant diabetes (Hazard Ratio= 1.04, 95% confidence interval 0.91 - 1.19). Similarly, no associations were observed for each class of induction immunosuppression agents and post-transplant diabetes. The use of contemporary induction immunosuppression in cardiac transplant patients was not associated with post-transplant diabetes.

Lymphoproliferative disorders after renal transplantation along 2 decades: a large longitudinal study of 21.546 recipients

IntroductionPost transplant lymphoproliferative disorders (PTLD) are heterogeneous lymphoid proliferations in recipients of solid organs which seem to be related to Epstein Barr Virus (EBV). The use of antilymphocyte antibodies, EBV seronegativity in the recipient,acute rejection and CMV infection have been identified as classical risk factors. Material y methodsWe have studied in a retrospective observational study, the incidence of PTLD in a period of 22 years, its relationship with EBV, presence of classical risk factors and outcome in 21546 simple adult renal transplant recipients from cadaveric and living donors, transplanted in 21 hospitals from 1990 to 2009. ResultsA total of 275 recipients developed PTLD (1,2%),195 males (70,9%), 80 females (29,1%) aged 59.2 (p25 44.7 p75 68)years. Two hundred forty-five (89.0%) were 1st transplant recipients and 269 (97,8%) from cadaveric donors. EBV in the tissue was reported in 94 out of the 155 studied recipients (60.6%) and 86.0% of the proliferations were due to B lymphocytes. PTLD median appearance after transplant were 42.months (p25, 75, 12, 77, 5). One hundred eighty-eight recipients out of 275 patients (68.3%) had any classical risk factor and the use of antilymphocyte antibodies was the most frequent.During the follow-up, 172 patients died (62,5%) and 103 (37,5%) had a complete remission. The main cause of death was PTLD progression (n = 91, 52,9%), followed by sepsis (n = 24, 13,9%). The follow-up period post-transplant of the recipients was between 3 and 22 years.The incidence was 0,14% during the first year post-trasplant and 0.98% the cumulative incidence at 10 years.Patient survival after diagnosis was 51%, 44% and 39% after 1, 2 and 5 years, respectively. Finally, overall graft survival was 48%, 39% and 33% at the same periods. ConclusionPTLD has a low incidence in renal transplant recipients. Most of the proliferations are due to B lymphocytes and seem to have a close relationship with EBV. PTLD can develop in the absence of classical risk factors. The prognosis is poor, mainly due to PTLD progression, but the survivors can even maintain their grafts.

Prevalence and complement activation of anti-lymphocyte IgM antibodies in hospitalized COVID-19 patients

Abstract Recent studies have shown that a proportion of COVID-19 patients develop auto-antibodies against a wide range of secreted and membrane proteins, some of which are expressed by lymphocytes. It is unclear, however, if and what proportion of patients might develop anti-lymphocyte antibodies (ALAb) and whether they might have cytotoxic function. We systematically characterized the presence, isotype and lytic function of ALAb in a cohort of 85 COVID-19 patients during hospital admission from May 2020 to June 2022. As controls we analyzed 20 healthy donors (HD) and seven Flu infected volunteers. Patients were assigned into mild (N=65), or moderate/severe (N=20) groups, based on oxygen requirements, and 37 patients were followed up after recovery. We found that 27% of COVID-19 patients had IgM ALAb (binding CD4, CD8 and/or B cells), compared to 15% of the control populations. IgM ALAb prevalence was independent of disease severity and persisted during early convalescence. Sera from some of the IgM ALAb positive COVID-19 patients, and not from the controls, induced complement dependent cytotoxicity (CDC) of HD PBMCs, mostly targeting B cells. Complement activation was corroborated by detecting complement deposition ex vivo on lymphocytes from 70% of COVID-19 acutely infected patients. The level of C3b deposition on CD4 T cells inversely correlated with CD4 numbers in blood of moderate/severe patients. Our findings indicate that the antibody mediated auto-immune response found in COVID-19 patients includes targeting of lymphocytes with potential contribution to the observed lymphopenia. This work was supported by the Divisions of Intramural Research of NIAID and NIBIB of the NIH

Major histocompatibility complex (MHC) antigens polymorphism and alloimmunization study in thalassemia patients with febrile non-hemolytic transfusion reaction (FNHTR).

HLA alloimmunization is one of the most troublesome consequence of regular transfusion which is itself a mainstay measure to provide longevity to the thalassemia patients. Febrile non-hemolytic transfusion reaction (FNHTR) is one of the most common complication which might be related to the HLA alloimmunization. Here, we studied the HLA antigenic system and alloimmunization rate in the Iranian β-thalassemia patients who suffered from FNHTR compare to the β-thalassemia patients without FNHTR. Total of 60 β-thalassemia patients with FNHTR (case group) and 20 β-thalassemia patients without FNHTR (control group) randomly have been selected and enrolled in the study. All were tested for HLA-A and -B loci by PCR-SSP method and also for the presence of anti-lymphocyte antibodies by LIFT method. Comparisons between two groups were performed by Pearson's χ2 test. Totally, a significant predominance was noted for two HLA alleles, HLA-A*24 (P=0.029) and B*55 (P=0.034) which have higher prevalence in control group. Although no significant association was found between the presence of anti-leukocyte antibodies and the development of FNHTR, the HLA-A*32 (P=0.047) allele was considered as possible genetic markers in the susceptibility to the development of anti-leukocyte antibodies. Here some evidences about the possible role of HLA polymorphism in susceptibility to FNHTR are provided. Those results indicated that HLA-A*24 and HLA-B*55 might play protective role on inducing FNHTR in β-thalassemia patients. Further studies which investigate the allele level of HLA-I alongside with specific reactivity of HLA-I antibodies might reveal more deep data about these phenomena.

New Complement Dependent Cytotoxicity Assay and its application to COVID-19 patient sera harboring anti-lymphocyte antibodies.

Abstract Complement dependent cytotoxicity (CDC) is one of the ways IgM and IgG antibodies can mediate the lysis of target cells, being IgM the antibody (Ab) isotype with the highest CDC activity. In a cohort of hospitalized COVID-19 patients we identified that 27% carried IgM anti-lymphocyte Ab in their sera. To quantify the sera potential lytic activity against healthy donor (HD) PBMC we developed a flow-based CDC assay with an internal negative control. The assay allows for normalization of the results and therefore inter-experiment data comparison without the need of using counting beads. In short, after CFSE labelling, 2 million PBMC are incubated with either complete media (CM) or with the different experimental conditions (Ab, sera, plasma), then they are washed thoroughly before adding them to equal numbers of unlabeled PBMC (internal negative control). This mixture of hot CFSE+ and cold CFSE-targets is then incubated with rabbit complement for an hour, stained and flow. A “ratio tube” containing the mixture with the CM incubated CFSE cells, is left without rabbit complement at 4 degrees and used to calculate the initial CFSE+/CFSE− ratio. We calculate the percentage of CDC lysis based on the CFSE+/CFSE− ratio in each tube after normalizing it to the ratio tube. Deploying this assay, we found CDC activity against B and T cells in five and two COVID-19 patients’ sera, respectively, out of 23 patients tested. This improved CDC assay shows high reproducibility and allows for quick, reliable, and easy test of multiple conditions. This work was supported by the Divisions of Intramural Research of NIAID, NIH

P415 Real-world data in Inflammatory Bowel Diseases on vedolizumab therapy: Interim analysis of the non-interventional LISTEN II study

Abstract Background Vedolizumab (VDZ) is a gut-selective anti-lymphocyte trafficking integrin antibody and is approved for treating patients with moderately to severely active UC (ulcerative colitis) and CD (Crohn’s disease) intravenously (IV) or subcutaneously (SC). The LISTEN II study aims to determine patient characteristics and effectiveness in patients treated with VDZ in a real-world setting. Methods LISTEN II is a multicentre, prospective non-interventional study in Germany. Adult patients with UC or CD, for whom the physician has decided to either initiate VDZ IV or switch from IV to SC, are included. Data on patient characteristics, modalities of VDZ use and disease activity (pMayo, HBI) are followed up quarterly for up to one year per routine practice. In addition, patient reported outcomes (PROs) confirmed as relevant in the previous LISTEN I study (e.g. rectal bleeding and general wellbeing) are recorded via an app (ePRO). Results Data of 198 UC patients (50% female, 6.0 years median disease duration) and 116 CD patients (56% female, 10.9 years median disease duration) with a mean age of 40 years were included in this interim analysis. VDZ treatment was newly initiated IV in 164 UC patients and 98 CD patients (start) and switched from IV to SC by 34 UC and 18 CD patients (switch) at study inclusion. At baseline corticosteroids were documented as used in 70% and 56% of UC and CD start-patients in the year prior to enrollment. Burden of disease was classified as high (pMayo>4) in 51% of UC patients at baseline and decreased to 15% at 3 months. For CD patients, proportion of high burdened patients (HBI>7) was 27% at baseline and 12% at month 3 (Figure 1). In this period, total mean pMayo score decreased in UC patients from 4.3±2.5 (start: 4.9±2.1; switch: 1.0±1.3) to 2.2±2.2 (start: 2.5±2.2; switch:1.0±1.6) and total mean HBI score from 5.4±4.4 (start: 5.8±4.5; switch: 3.5±3.7) to 3.3±3.4 (start: 3.4±3.4, switch: 2.8±3.3) in CD patients (Figure 2). UC patients using the ePRO (N=152, mean age: 39 years, 49% female) reported from ePRO initiation up to month 3 a mean score decrease for rectal bleeding (range 0-3) from 1.3 to 0.6, for general well-being (range 0-4) from 1.7 to 1.3 and for impact on work productivity (range 0-10) from 3.7 to 2.3 points. Conclusion LISTEN II real-world data support the effectiveness of VDZ treatment in UC and CD patients. Patients starting VDZ IV showed a higher disease activity at baseline which decreased under VDZ treatment. Switching of VDZ IV to SC was mainly performed in patients with low disease burden under VDZ treatment, resulting in maintained therapeutic effectiveness. Also PROs of UC patients show an improvement supporting benefit with VDZ treatment.

P629 Real-life treatment persistence and treatment outcomes of Finnish patients with Inflammatory Bowel Disease receiving vedolizumab as first-line biological treatment

Abstract Background Vedolizumab is a gut selective anti-lymphocyte trafficking monoclonal antibody directed towards the integrin α 4β 7. The efficacy and safety of vedolizumab in the treatment of adults with moderately to severely active Crohn’s disease (CD) or ulcerative colitis (UC) are well-established in randomized clinical trials and real-world evidence studies. However, real-world data are limited on vedolizumab therapy used on biological naïve CD and UC patients. Here, we analyse treatment persistence, treatment outcomes, and reasons for treatment discontinuation of vedolizumab as a first-line biological treatment in CD and UC patients in a Finnish real-world setting. Methods This was an observational, retrospective, multi-centre registry study. The cohort included all adult (≥ 18 years of age) patients with a diagnosis of CD or UC who initiated vedolizumab as a first-line biological treatment between May 2014, and June 2020, in the five Finnish university hospital districts. Clinical data were collected from electronic health records. The Prescription Register by the Finnish Social Insurance Institution was the data source for prescribed IBD treatments. Treatment persistence was defined as the time from initiation to discontinuation of therapy. P-values were calculated by using paired t-test. Results The cohort consisted of 54 CD and 69 UC patients treated with vedolizumab as a first-line biological treatment. The mean ages were 61.9 and 56.8 years for CD and UC at the time of vedolizumab start, respectively. Disease duration was 10.9 years in CD and 10.5 years in UC. Altogether, 35.8% of patients had a history of cancer. At month 12, treatment persistence was 84.9% (n=44) in CD and 64.7% (n=41) in UC cohorts (Figure 1). Most vedolizumab discontinuations (CD, n=11; UC, n=26) were due to lack of efficacy, and treatment discontinuations due to adverse events were rare (n<5). Vedolizumab was associated with favourable treatment outcomes, as indicated by efficacy improvements at 12 months compared with baseline in Harvey-Bradshaw Index (CD, 3.2 vs 4.9, p=0.025), Partial Mayo Score (UC, 3.8 vs 5.1, p=0.021), Physician’s Global Assessment (CD, 0.9 vs 1.8, p<0.001; and UC, 0.4 vs 2.1, p<0.001) scores, and positive endoscopic Mayo Score (UC, 0.7 vs 2.2, p<0.001) and biochemical outcomes. Conclusion Vedolizumab showed high treatment persistence and positive treatment outcomes such as improvements in efficacy, endoscopic activity, and biochemical parameters when used as the first-line biological treatment.

631P A meta-analysis of the outcome of post-transplant lymphoproliferative disorder in adult patients after hematopoietic stem cell transplant

Post-transplant lymphoproliferative disorder is a fatal complication that can occur early after solid organ or hematopoietic stem cell transplantation (HSCT). It represents a spectrum of Epstein Barr virus (EBV)-related clinical diseases, from benign mononucleosis like illness to malignancies like non-Hodgkin's lymphoma. Some of the established risk factors for PTLD are HLA mismatching, T-cell depletion, and the use of anti-lymphocyte antibodies as conditioning or immunosuppression for the treatment of graft-versus-host disease.

P1623: ROLE OF HLA GENES IN DEVELOPMENT OF HLA-ALLOIMMUNIZATION IN BLOOD RECIPIENTS

Background: The main adverse effects of HLA-alloimmunization are transfusion failure and the need for additional platelet transfusions, febrile reactions, and the threat of fatal bleeding. The individual prediction of the risk of alloimmunization remains an unresolved problem. It seems relevant to study the relationship between the HLA genotype and the probability of alloimmunization of recipients as a result of blood transfusions. Aims: Assess the genetic predisposition of recipients to the development of HLA alloimmunization. Methods: Immunohematological and genetic studies were performed in 61 patients (22 men and 39 women) who received from 6 to 32 transfusions of blood components (median 11) during the previous treatment in a hematology clinic in 2019-2021. All blood components were leukoreduced. Patient age ranged from 3 to 78 years (median 48 years). Acute leukemia was diagnosed in 34 patients, myelodysplastic syndrome - in 10, aplastic anemia - in 8, other blood diseases - in 9. Typing of HLA DRB1, DQA1, DQB1 gene was performed by real-time polymerase chain reaction using equipment and reagents from DNA- technology (Russia). Statistical analysis was performed using the chi-square test. Results: Based on the results of the study of antilymphocyte antibodies, patients were divided into two groups: HLA-nonimmunized (n=31) and HLA-immunized (n=30). The Panel Reactive Antibody in 3 out of 30 alloimmunized patients was 25-49%, in 12 - 50-74%, in 15 patients - 75-100%. When analyzing the results of immunogenetic examination, statistical differences were established in the frequency of detection of HLA-alleles and haplotypes in the genotypes of HLA-alloimmunized and nonimmunized recipients (Table). Table. - Frequency of detection of HLA-DRB1-DQA1-DQB1 haplotypes in HLA-alloimmunized and HLA-non-alloimmunized patients HLA-DRB1-DQA1-DQB1 haplotypes Frequency of detection of HLA haplotypes p HLA-nonalloimmunized patients, n=31 HLA- alloimmunized patients, n=30 абс. % абс. DRB1*15-DQA1*01:02-DQB1*06:02-8 14 45.2 7 23.3 0.12 DRB1*01-DQA1*01:01-DQB1*05:01 12 38.7 9 30 0.65 DRB1*03-DQA1*05:01-DQB1*02:01 2 6.5 8 26.7 0.07 DRB1*04-DQA1*03:01-DQB1*03:02 1 3.2 9 30 0.01 DRB1*07-DQA1*02:01-DQB1*02:01 4 12.9 6 20 0.69 DRB1*13-DQA1*01:03-DQB1*06:02-8 3 9.7 7 23.3 0.27 DRB1*16-DQA1*01:02-DQB1*05:02 6 19.4 0 0 0.03 DRB1*11-DQA1*05:01-DQB1*03:01 3 9.7 4 13.3 0.96 Summary/Conclusion: A genetically determined predisposition to the development of HLA-alloimmunization as a result of blood transfusions is associated with the presence of HLA-alleles DRB1*04, DQA1*03:01, DQA1*05:01 and HLA-haplotype DRB1*04-DQA1*03:01-DQB1*03:02 in the genotypes of recipients. The probability of antibody production is reduced in patients with HLA-alleles DRB1*16, DQA1*01:02, DQB1*05:02 and HLA-haplotype DRB1*16-DQA1*01:02-DQB1*05:02.

Enfermedad linfoproliferativa difusa postrasplante renal: estudio longitudinal de 21.546 receptores durante 2 décadas en España

IntroductionPosttransplant lymphoproliferative disorders (PTLD) are heterogeneous lymphoid proliferations in recipients of solid organs which seem to be related to Epstein-Barr virus. The use of antilymphocyte antibodies, Epstein-Barr virus seronegativity in the recipient, acute rejection and CMV infection have been identified as classical risk factors. Material and methodsWe have studied, in a retrospective observational study, the incidence of PTLD in a period of 22 years, its relationship with Epstein-Barr virus, presence of classical risk factors and outcome in 21,546 simple adult renal transplant recipients from cadaveric and living donors, transplanted in 21 hospitals from 1990 to 2009. ResultsA total of 275 recipients developed PTLD (1.2%), 195 males (70.9%), 80 females (29.1%), aged 59.2 (p25 44.7; p75 68) years. Two hundred forty-five (89.0%) were first transplant recipients and 269 (97.8%) from cadaveric donors. Epstein-Barr virus in the tissue was reported in 94 out of the 155 studied recipients (60.6%) and 86.0% of the proliferations were due to B lymphocytes. PTLD median appearance after transplant were 42 (p25 12; p75 77.5) months. One hundred eighty-eight recipients out of 275 patients (68.3%) had any classical risk factor and the use of antilymphocyte antibodies was the most frequent. During the follow-up, 172 patients died (62.5%) and 103 (37.5%) had a complete remission. The main cause of death was PTLD progression (n=91, 52,9%), followed by sepsis (n=24, 13.9%). The follow-up period post-transplant of the recipients was between 3 and 22 years.The incidence was 0.14% during the first year post-trasplant and 0.98% the cumulative incidence at 10 years.Patient survival after diagnosis was 51, 44 and 39% after one, 2 and 5 years, respectively. Finally, overall graft survival was 48, 39 and 33% at the same periods. ConclusionPTLD has a low incidence in renal transplant recipients. Most of the proliferations are due to B lymphocytes and seem to have a close relationship with Epstein-Barr virus. PTLD can develop in the absence of classical risk factors. The prognosis is poor, mainly due to PTLD progression, but the survivors can even maintain their grafts.

Prevalence of Anti-lymphocyte Antibodies in Patients with Good Syndrome and Partial RAG Deficiency

Good syndrome (GS) is a rare adult-onset progressive combined immunodeficiency typically characterized by thymoma, hypogammaglobulinemia and variable CD4+ lymphocytopenia. Of note, opportunistic infections and autoimmune complications have been increasingly recognized in these patients, implying underlying immune dysregulation. Autoantibody profiling, including the prevalence of antibodies targeting cytokines (associated with thymoma) and lymphocytes (associated with pathogenic lymphocytopenia) remains unclear.

Abstract 11003: Racial Disparities in Induction Immunosuppression Use Among Heart Transplant Recipients in the United States

Introduction: Black heart transplant recipients have higher rates of acute rejection, graft failure, and mortality compared to other races. Induction immunosuppression in the immediate peri-transplant period may lower the risk of acute rejection among high-risk patients, including Black transplant recipients. However, it is not known whether the odds of receiving this treatment are different across races. Therefore, we evaluated whether there are disparities in the use of induction immunosuppression following heart transplants among Black patients compared to other races. Methods: We conducted a cross-sectional study of U.S. adults in the Scientific Registry of Transplant Recipients who received their first heart transplant between 2008 - 2018. We used mixed-effects logistic regression to compare the odds of receiving induction immunosuppression agents (IL-2 receptor antagonists, polyclonal anti-lymphocyte antibodies, and CD52 monoclonal antibodies) across different races. Results: Among 23,935 adult heart transplant recipients, 5,160 (21.6%) were Black, including 2,797 (54.2%) who received induction immunosuppression, and 18,775 (78.4%) were non-Black, including 9,499 (50.6%) who received induction immunosuppression. After accounting for demographic and clinical characteristics and treatment center, Black race was associated with 28% higher odds (Odds Ratio=1.28, 95% CI 1.17-1.40) of induction immunosuppression use compared to other races. Similar results were observed when race was further stratified (Table 1). Conclusions: In our study, Black heart transplant recipients were more likely to receive induction immunosuppression than transplant recipients of other races. However, further research on post-transplant clinical outcomes including survival following induction immunosuppression among Black patients is needed to formulate treatment guidelines.

Pneumocystis jirovecii: The Changing Landscape for Prophylaxis.

Pneumocystis jirovecii: The Changing Landscape for Prophylaxis.

Rituximab identified as an independent risk factor for severe PJP: A case-control study.

ObjectivePneumocystis jirovecii pneumonia (PJP) was reported among immunosuppressed patients with deficits in cell-mediated immunity and in patients treated with immunomodulatory drugs. The aim of this study was to identify risk-factors for PJP in noninfected HIV patients.MethodsThis retrospective, test negative, case-control study was conducted in six hospitals in Israel, 2006–2016. Cases were hospitalized HIV-negative patients with pneumonia diagnosed as PJP by bronchoalveolar lavage. Controls were similar patients negative for PJP.ResultsSeventy-six cases and 159 controls were identified. Median age was 63.7 years, 65% males, 34% had hematological malignancies, 11% inflammatory diseases, 47% used steroids and 9% received antilymphocyte monoclonal antibodies. PJP was independently associated with antilymphocyte monoclonal antibodies (OR 11.47, CI 1.50–87.74), high-dose steroid treatment (OR 4.39, CI 1.52–12.63), lymphopenia (OR 8.13, CI 2.48–26.60), low albumin (OR 0.15, CI 0.40–0.54) and low BMI (OR 0.80, CI 0.68–0.93).ConclusionIn conclusion, rituximab, which is prescribed for a wide variety of malignant and inflammatory disorders, was found to be significant risk-factor for PJP. Increased awareness of possible PJP infection in this patient population is warranted.

Immunosuppressive Management of Pediatric Kidney Transplant Recipients.

Kidney transplantation is a preferable treatment of children with end-stage kidney disease. All kidney transplant recipients, including pediatric need immunosuppressive medications to prevent rejection episodes and graft loss. Induction therapy is used temporarily only immediately following transplantation while maintenance immunosuppressive drugs are started and given long-term. There is currently no consensus regarding the use of induction therapy in children; its use should be decided based on the immunological risk of the child. The recent progress shows that the recommended strategy is to use as maintenance immunosuppressive therapy a combination of a calcineurin inhibitor (preferably tacrolimus) with an antiproliferative drug (preferably mycophenolate mofetil) with steroids that can be withdrawn early or late in low-risk children. The mTOR-inhibitors (sirolimus, everolimus) are used rarely in pediatrics because of common side effects and no evidence of a benefit over calcineurin inhibitors. The use of calcineurin inhibitors, mycophenolate, and mTOR-inhibitors should be followed by therapeutic drug monitoring. Immunosuppressive therapy of acute rejection consists of high-dose steroids and/or anti-lymphocyte antibodies (T-cell mediated rejection) or plasma exchange, intravenous immunoglobulines and/or rituximab (antibodymediated rejection). The future strategies for research are mainly precise characterisation of children needing induction therapy, more specific indications for mTOR-inhibitors and for the far future, the possibility to reach the immuno tolerance.

Prominent antibody mediated auto-immune response in idiopathic CD4 lymphopenic patients

Abstract Patients with Idiopathic CD4 Lymphocytopenia (ICL) have low circulating CD4 T cell numbers, accompanied sometimes by low numbers of CD8, B and/or NK cells, making them susceptible to opportunistic infections. The etiology is unknown and there is no familiar linkage. In spite of their immune deficiency 32% of ICL patients have clinically defined auto-immune disease. To analyze the presence of auto-antibodies in these patients we hybridized sera from 34 patients and 15 healthy control (HC) to a 9,000 proteins human array. When identifying positive targets as the ones with Z score ≥4 we found that all 34 ICL patients, unrelated to their autoimmune disease manifestations, had IgG antibodies against tens of proteins while the HC had none. There was considerable variability in both numbers and identities of targets. We next evaluated whether some of these antigens might be displayed on the T cell membrane. Using a flow-based assay we tested sera from 72 ICL patients and found that 50% of them had either IgG, mostly but not exclusively IgG1 and/or IgG4 isotypes, or IgM antibodies against T cell membrane proteins. Functionally, 50% of the plasma with IgG1 or IgG3 antibodies induced antibody dependent cell mediated cytotoxicity against healthy T-lymphocytes. In addition, sera from 20% of the patients with anti-lymphocyte antibodies induced complement deposition on healthy CD3 T cells and some of them induced complement dependent cytotoxicity. Furthermore, we observed complement deposition (C1q, C4c and C3b) on CD4 T cells in 14% of the 72 ICL patients when analyzed directly ex vivo. Our data support a high prevalence and pathogenicity of autoantibodies in ICL, which offers a potential therapeutic target.

SUN-357 RABBIT ANTI-THYMOCYTE GLOBULIN INDUCTION THERAPY IN RENAL TRANSPLANTATION

Rabbit anti-thymocyte globulin (rATG) is a preparation of polyclonal antilymphocyte antibodies. It is used not only as an induction therapy to decrease delayed function or rejection of the graft, but also to reverse rejection, with slightly higher rates of complications such as infections and malignancy. The purpose of this study is to review the experience on the use of thymoglobulin as induction treatment in patients with renal transplantation in Cuenca, Ecuador. A retrospective study was conducted in a series of cases (June-September 2019) in the Departament of Nephrology. Universe consisted of 10 patients who underwent renal transplantation from cadaveric donors. All patients received Thymoglobulin induction (daily dose 1,5mg/Kg; 4 patients for 3 days and 6 patients for 5 days), tacrolimus (initial dose 0,075mg/kg per day; if renal function allowed it, dose was adjusted at day five after surgery, increasing it to 1mg/kg per day), mycophenolate (2g/day), and methylprednisolone (inicial daily dose 250mg intravenous for 3 days, then progressive decrease until reaching 20mg daily at first month of follow-up). Leukocyte, lymphocyte, platelet, hemoglobin, urea and creatinine levels were evaluated at five, ten and thirty days after transplantation. Patients age ranked between 20-60 years old (average of 38) and where predominantly female (70%). Hemodialysis (60%). Hypertension was the first cause of renal disease (30%) and cold ischemia time was between 5 to 10 hours. There was an average 50% histocompatibility between donor and recipient. Peak panel-reactive antibody presented in 4% cases. Marked lymphopenia and anemia were evidenced at 5 days with recovery at 10 and 30 days after transplantation. None showed platelet disease. Recovery of renal function became evident from day 5 (1.6mg/dl) presenting at 30 days an improved function of 1.27mg/dl. Infection rate was 50%. In this study, the use of thymoglobulin dose for 3 to 5 days does not represent a risk for infections, so it is considered effective and safe.