| 1. |
- Jordan, Stanley C., et al.
(författare)
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Imlifidase desensitization in crossmatch-positive, highly-sensitized kidney transplant recipients : Results of an international phase 2 trial (Highdes)
- 2021
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Ingår i: Transplantation. - 0041-1337 .- 1534-6080. ; 105:8, s. 1808-1817
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Highly-HLA sensitized patients have limited access to life-saving kidney transplantation due to a paucity of immunologically suitable donors. Imlifidase is a cysteine protease that cleaves IgG leading to a rapid decrease in antibody level and inhibition of IgG-mediated injury. This study investigates the efficacy and safety of imlifidase in converting a positive crossmatch test to negative, allowing highly sensitized patients to be transplanted with a living or deceased donor kidney.METHODS: This open-label, single arm, phase 2 trial conducted at five transplant centers, evaluated the ability of imlifidase to create a negative crossmatch test within 24 hours. Secondary endpoints included post-imlifidase DSA levels compared to pre-dose levels, renal function, and pharmacokinetic/pharmacodynamic profiles. Safety endpoints included adverse events and immunogenicity profile.RESULTS: 89.5% of the transplanted patients demonstrated conversion of baseline positive crossmatch to negative within 24 hours after imlifidase treatment. DSA most often rebounded 3-14 days post-imlifidase dose, with substantial interpatient variability. Patient survival was 100% with graft survival of 88.9% at 6 months. 38.9% had early biopsy proven antibody mediated rejection with onset 2-19 days post-transplantation. Serum IgG levels began to normalize after ~3-7 days post-transplantation. Anti-drug antibody levels were consistent with previous studies. Seven adverse events in six patients were classified as possibly or probably related to treatment and were mild-moderate in severity.CONCLUSIONS: Imlifidase was well tolerated, converted positive crossmatches to negative, and enabled patients with a median cPRA of 99.83% to undergo kidney transplantation resulting in good kidney function and graft survival at 6 months.
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| 2. |
- Kjellman, Christian, et al.
(författare)
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Outcomes at 3 years posttransplant in imlifidase-desensitized kidney transplant patients
- 2021
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Ingår i: American Journal of Transplantation. - : Elsevier. - 1600-6135 .- 1600-6143. ; 21:12, s. 3907-3918
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Tidskriftsartikel (refereegranskat)abstract
- Imlifidase is a cysteine proteinase which specifically cleaves IgG, inhibiting Fc-mediated effector function within hours of administration. Imlifidase converts a positive crossmatch to a potential donor (T cell, B cell, or both), to negative, enabling transplantation to occur between previously HLA incompatible donor-recipient pairs. To date, 39 crossmatch positive patients received imlifidase prior to a kidney transplant in four single-arm, open-label, phase 2 studies. At 3 years, for patients who were AMR+ compared to AMR-, death-censored allograft survival was 93% vs 77%, patient survival was 85% vs 94%, and mean eGFR was 49 ml/min/1.73 m2 vs 61 ml/min/1.73 m2 , respectively. The incidence of AMR was 38% with most episodes occurring within the first month post-transplantation. Sub-analysis of patients deemed highly sensitized with cPRA ≥ 99.9%, and unlikely to be transplanted who received crossmatch-positive, deceased donor transplants had similar rates of patient survival, graft survival, and eGFR but a higher rate of AMR. These data demonstrate that outcomes and safety up to 3 years in recipients of imlifidase-enabled allografts is comparable to outcomes in other highly sensitized patients undergoing HLA-incompatible transplantation. Thus, imlifidase is a potent option to facilitate transplantation among patients who have a significant immunologic barrier to successful kidney transplantation.
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| 3. |
- Almstrand, Ann-Charlotte, et al.
(författare)
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An explorative study on respiratory health among operators working in polymer additive manufacturing
- 2023
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Ingår i: Frontiers in Public Health. - : Frontiers Media S.A.. - 2296-2565. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Additive manufacturing (AM), or 3D printing, is a growing industry involving a wide range of different techniques and materials. The potential toxicological effects of emissions produced in the process, involving both ultrafine particles and volatile organic compounds (VOCs), are unclear, and there are concerns regarding possible health implications among AM operators.The objective of this study was to screen the presence of respiratory health effects among people working with liquid, powdered, or filament plastic materials in AM. MethodsIn total, 18 subjects working with different additive manufacturing techniques and production of filament with polymer feedstock and 20 controls participated in the study. Study subjects filled out a questionnaire and underwent blood and urine sampling, spirometry, impulse oscillometry (IOS), exhaled NO test (FeNO), and collection of particles in exhaled air (PEx), and the exposure was assessed. Analysis of exhaled particles included lung surfactant components such as surfactant protein A (SP-A) and phosphatidylcholines. SP-A and albumin were determined using ELISA. Using reversed-phase liquid chromatography and targeted mass spectrometry, the relative abundance of 15 species of phosphatidylcholine (PC) was determined in exhaled particles. The results were evaluated by univariate and multivariate statistical analyses (principal component analysis). ResultsExposure and emission measurements in AM settings revealed a large variation in particle and VOC concentrations as well as the composition of VOCs, depending on the AM technique and feedstock. Levels of FeNO, IOS, and spirometry parameters were within clinical reference values for all AM operators. There was a difference in the relative abundance of saturated, notably dipalmitoylphosphatidylcholine (PC16:0_16:0), and unsaturated lung surfactant lipids in exhaled particles between controls and AM operators. ConclusionThere were no statistically significant differences between AM operators and controls for the different health examinations, which may be due to the low number of participants. However, the observed difference in the PC lipid profile in exhaled particles indicates a possible impact of the exposure and could be used as possible early biomarkers of adverse effects in the airways.
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| 4. |
- Järnum, S., et al.
(författare)
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Effects of IdeS on HLA-SAB, C1q-SAB and CDC-XM
- 2018
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Ingår i: American Journal of Transplantation. - : John Wiley & Sons. - 1600-6135 .- 1600-6143. ; 18:S4: Oral Abstracts, s. 370-371
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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