Acute cellular rejection (ACR) frequently occurs following lung transplantation (LuTx) and represents a risk factor for the development of chronic lung allograft dysfunction (CLAD) as well as long-term survival. The histopathological diagnosis of ACR carries a burden of interobserver variability. The widespread utilization and cost-effectiveness of immunohistochemistry (IHC) was proven beneficial in diagnosing rejection in human kidney transplantations and LuTx rat models. However, its potential for ACR detection in patients remains unexplored. We analyzed surface markers (CD3, CD4, CD8, CD20, CD68, CD47, PD-1, PD-L1, and CD31/PECAM-1) on lung tissue cryobiopsy samples collected within 6 months post-LuTx from 60 LuTx recipients, 48 of whom were diagnosed with ACR. Additionally, serum samples from 51 patients were analyzed using a multiplex bead-based Luminex assay. The cytokines and markers included PD-L1, IL2, TNFα, IFNγ, and Granzyme B. We observed a significant increase in PD-L1 tissue expression within the rejection group, suggesting a concerted effort to suppress immune responses, especially those mediated by T-cells. Furthermore, we noted significant differences in PECAM-1 levels between ACR/non-ACR. Additionally, peripheral blood C-reactive-protein levels tended to be higher in the ACR group, while Luminex serum analyses did not reveal any significant differences between groups. In conclusion, our findings suggest the potential value of PECAM-1 and PD-L1 markers in diagnosing ACR.
- MeSH
- akutní nemoc MeSH
- antigeny CD274 * metabolismus krev MeSH
- antigeny CD31 * metabolismus MeSH
- biologické markery * krev metabolismus MeSH
- dospělí MeSH
- imunohistochemie MeSH
- lidé středního věku MeSH
- lidé MeSH
- plíce patologie MeSH
- rejekce štěpu * diagnóza krev MeSH
- senioři MeSH
- transplantace plic * škodlivé účinky MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Booster doses of SARS-CoV-2 mRNA vaccines are commonly used in kidney transplant recipients (KTRs). However, there is uncertainty regarding the waning of vaccination responses and immunological safety in KTRs. METHODS: A total of 123 KTRs were included in the final analysis of this prospective observational cohort study. The aim was to evaluate the immunogenicity and immunological safety. SARS-CoV-2 antispike IgG antibodies and anti-HLA antibodies were measured at baseline and then at months 3, 6, and 12 after vaccination with the first booster dose (ie, the third vaccine dose). Antibodies against S1 and S2 subunits of SARS-CoV-2 were evaluated using an immunochemiluminescent assay (cutoff 9.5 AU/mL, sensitivity 91.2%, and specificity 90.2%). Anti-HLA antibodies were analyzed using single-antigen bead technology. RESULTS: Seroconversion was reached in 65% of KTRs previously nonresponding to 2-dose mRNA vaccination; the overall seroconversion rate 3 mo after the first booster dose was 83%. Vaccination induced a durable humoral response, and the antibody levels were stable during the 12-mo study follow-up. Higher age (exponentiated beta coefficient [eβ] 0.97; 95% confidence interval [CI], 0.943-0.997) and a full dose of mycophenolate (eβ 0.296; 95% CI, 0.089-0.984) were negatively associated with SARS-CoV-2 IgG antibody levels, whereas better graft function (eβ1.021; 95% CI, 1.005-1.037) was associated positively. There were no systematic signs of anti-HLA antibody development after vaccination. However, during the follow-up, there was a nonsignificant signal of an increase in anti-HLA antibodies in those who developed COVID-19. CONCLUSIONS: Additional booster doses of SARS-CoV-2 mRNA vaccines induce durable antibody response even in a large subset of previous nonresponders and are not associated with the risk of allosensitization. Furthermore, a signal linking COVID-19 to the development of anti-HLA antibodies was observed, and this should be confirmed and further examined (NCT05483725).
- Publikační typ
- časopisecké články MeSH
PURPOSE: There are no clear guidelines on how to handle immunosuppression in lung transplant recipients (LTRs) infected by SARS-CoV-2. Antimetabolite reduction with corticosteroid escalation is the most frequent strategy. The aim of this study was to determine the effect of this therapeutic approach on the incidence of de novo donor specific-antibodies (dnDSA). METHODS: We retrospectively analysed a cohort of 27 LTRs diagnosed with SARS-CoV-2 infection between September 2020 and April 2021 with available anti-HLA antibodies screening before and after infection. Managed as per the centre's SARS-CoV-2 protocol, the treatment modalities included specific virostatic treatment, convalescent plasma administration, reduction or discontinuation of mycophenolate and transient corticosteroid escalation initiated in the second week post-infection. RESULTS: All 27 patients received virostatics: 15 (55.6%) remdesivir and 12 (44.4%) favipiravir. In addition, 18 patients (66.7%) underwent convalescent plasma therapy. Of the 27 patients, 25 (92.6%) received mycophenolate as a part of their maintenance immunosuppressive regimen, which was temporarily reduced in 10 (37%) and discontinued in 15 LTRs (55.6%), the median resumption times for mycophenolate daily doses of at least 1000 mg being 13 days (IQR 11.0-63.5) and 59 days (IQR 26.0-130.0), respectively. Corticosteroids were escalated in 25 patients (92.6%), of whom 9 (33.3%) received IV methylprednisolone (median 80 mg/day; IQR 80-187.5) and 16 (59.3%) had oral prednisone adjusted (median 20 mg/day; IQR 16.3-38.8). The median time to revert to the corticosteroid dosage of ≤20 mg/day was 42 days (IQR 36.0-87.0). Notably, no dnDSA were detected in any LTR between 1 and 9 months from the onset of the SARS-CoV-2 infection. CONCLUSION: Our findings suggest that antimetabolite cessation with a transient corticosteroid escalation is a safe therapeutic strategy regarding anti-HLA dynamics in SARS-CoV-2 infected LTRs.
- MeSH
- antilymfocytární sérum MeSH
- antimetabolity MeSH
- COVID-19 * epidemiologie MeSH
- hormony kůry nadledvin terapeutické užití MeSH
- imunosupresiva terapeutické užití MeSH
- incidence MeSH
- lidé MeSH
- plíce MeSH
- příjemce transplantátu MeSH
- protilátky MeSH
- retrospektivní studie MeSH
- SARS-CoV-2 MeSH
- sérologická léčba covidu-19 MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Protilátkami zprostředkovaná (humorální) rejekce je závažná komplikace, která je asociována se zhoršenou prognózou přežití transplantovaných orgánů. Její diagnostika byla dlouho zaměřena na detekci protilátek specifických proti HLA antigenům, nicméně se v posledních letech ukázalo, že při rozvoji této rejekce mohou hrát roli i protilátky proti antigenům, které jsou kódovány geny mimo HLA komplex. Non HLA antigeny jsou polymorfní molekuly, a proto mohou být rozpoznány imunitním systémem příjemců orgánů. Tyto antigeny se vyskytují na povrchu endoteliálních a epiteliálních buněk, ale mohou být lokalizovány i intracelulárně a uvolňovat se v případě buněčné lýze. Mezi non HLA antigeny patří molekuly MICA – major-histocompatibility-complex (MHC) class I-related chain A, receptor angiotensinu II-R1, kolagen, K-α1 tubulin, srdeční myosin, vimentin a další. Non HLA protilátky se mohou vyskytovat před transplantací, ale rovněž mohou být produkovány i de novo. Diagnostika non HLA protilátek se provádí za využití xMap technologie (Luminex) nebo endoteliálním crossmatch (křížová zkouška) a dalšími technikami. Nicméně všechny metodiky i interpretace výsledků non HLA má svá úskalí.
Antibody-mediated (humoral) rejection (AMR) is a serious complication that is associated with a worse prognosis of survival of transplanted organs. The diagnosis of AMR has been long time focused on the detection of antibodies specific to HLA antigens, however, in recent years it has become clear that antibodies against antigens encoded by genes outside the HLA complex can also play a role in the development of AMR. Non-HLA antigens are polymorphic molecules and therefore can be recognised by the immune system of organ transplant recipients. These antigens are expressed on the surface of endothelial and epithelial cells, but can also be localised intracellularly and released in case of cell lysis. Non-HLA antigens include molecules MICA – major-histocompatibility-complex (MHC) class I-related chain A, angiotensin II-R1 receptor (ATR1), collagen, K-α1 tubulin, cardiac myosin, vimentin and others. Non-HLA antibodies can occur before transplantation, but may also be produced de novo. The diagnosis of non-HLA antibodies is carried out using xMap technology (Luminex), the so-called endothelial crossmatch and other techniques, however, all methodologies and interpretation of results have their pitfalls.
- Klíčová slova
- non HLA protilátky, technologie Luminex,
- MeSH
- autoprotilátky klasifikace škodlivé účinky toxicita MeSH
- HLA antigeny * imunologie MeSH
- lidé MeSH
- rejekce štěpu diagnóza etiologie komplikace MeSH
- testování histokompatibility metody MeSH
- transplantace orgánů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
- Klíčová slova
- non HLA protilátky, technologie Luminex,
- MeSH
- autoprotilátky * klasifikace škodlivé účinky toxicita MeSH
- HLA antigeny imunologie MeSH
- lidé MeSH
- rejekce štěpu diagnóza etiologie komplikace MeSH
- testování histokompatibility metody MeSH
- transplantace orgánů * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
The ELISpot assay is a sensitive technique applied to assess cytokine-producing memory/effector T cells and human leukocyte antigens (HLA)-specific IgG-producing B cells. Besides the fact that the method is laborious and is difficult to standardise between laboratories, it may provide valuable information on the immune response of recipients before and after organ transplantation. In this article, we briefly review the recent literature and discuss the clinical significance of the ELISpot assay in predicting the risk and incidence of allograft rejection and survival.
- MeSH
- ELISPOT MeSH
- interferon gama MeSH
- lidé MeSH
- rejekce štěpu * MeSH
- T-lymfocyty MeSH
- transplantace ledvin * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
