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The aim of this prospective study was to assess the duration of culture-viable SARS-CoV-2 and to monitor the emergence of mutations in a cohort of 23 kidney transplant recipients (KTRs) from June 2022 to June 2023. Combined nares/oropharyngeal swabs were collected weekly starting as soon as possible after symptom onset. The time from symptom onset to a negative culture was 11 days (interquartile range, 8-14), while the time to negative reverse transcriptase quantitative polymerase chain reaction was 18 days (interquartile range, 15-30). Beyond the first swab, 21.7% had a positive culture, and 8.7% replicated viable virus for longer than 30 days. T cell depletion (rate ratio, 2.5; 95% confidence interval [95% CI], 1.9-3.3; P < .001) and time from transplantation (rate ratio, 0.93; 95% CI, 0.90-0.97; P = .006) were associated with the time of viable virus shedding. A cycle threshold value of 24.2 demonstrated a 91.3% negative predictive value of viability (95% credible interval [95% CrI], 76-100). The odds of viability decreased by 69% per week of infection (odds ratio, 0.31; 95% CrI, 0.12-0.76). Overall, ribonucleic acid sequencing did not show accelerated molecular evolution though mutation rate could be increased in molnupiravir-treated KTRs. In conclusion, viable SARS-CoV-2 is eliminated rapidly, the risk of virus evolution is low, and prolonged self-isolation is generally unnecessary for most KTRs., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Copyright © 2024 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of competing interest ZD: received consultancy fees/lecture fees/fees for attending advisory boards from ALK, Antabio, Foresee Pharmaceuticals, GlaxoSmithKline, Hippo-Dx, QPS-Netherlands, Sanofi-Genzyme; she served as Director Respiratory & Allergy at QPS-NL and this CRO received research grants for clinical trials from HAL Allergy, Janssen Research & Development LLC, Patara pharma, Cerbios, Merck Sharp & Dohme, Novartis, Foresee Pharmaceuticals and ERA4TB (IMI-project). MJ: ALK, Stallergenes-Greer, Chiesi, GSK, Pfizer, Novartis, AstraZeneca and SANOFI. NH: Received honoraria for serving as advisor or consultant for GSK, AstraZeneca, Sanofi, Regeneron, Amgen, Genentech, Novartis and Teva. His institution received research grant support of his behalf from GSK, Genentech, Sanofi, Teva, Novartis, and AstraZeneca. LH: Has received grant funding, participated in advisory boards and given lectures at meetings supported by Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, Circassia, Hoffmann la Roche, GlaxoSmithKline, Novartis, Theravance, Evelo Biosciences, Sanofi, and Teva; he has received grants from MedImmune, Novartis UK, Roche/ Genentech Inc, and Glaxo Smith Kline, Amgen, Genentech/Hoffman la Roche, Astra Zeneca, MedImmune, Glaxo Smith Kline, Aerocrine and Vitalograph; he has received sponsorship for attending international scientific meetings from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK and Napp Pharmaceuticals; he has also taken part in asthma clinical trials sponsored by AstraZeneca, Boehringer Ingelheim, Hoffmann la Roche, and GlaxoSmithKline for which his institution received remuneration; he is the Academic Lead for the Medical Research Council Stratified Medicine UK Consortium in Severe Asthma which involves industrial partnerships with a number of pharmaceutical companies including Amgen, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Hoffmann la Roche, and Janssen. RD: Declares consulting fees from Synairgen, Sanofi and Galapagos, lecture fees from GSK, AZ and Airways Vista and he holds shares from Synairgen. DR: No COIs related to this work. SQ: ALK, Allergy Therapeutics, AstraZeneca, Chiesi, GSK, Leti, Mundipharma, Novartis, Sanofi-Genzyme, Teva. VB: Has worked as advisor, supervisor, investigator of pharmaceutical studies, unrestricted grants, and others with: AstraZeneca, GSK, MSD & Shering Plough, ALK-Abello; Chiesi,Novartis, Pharmaxis, Pfizer, Boehringer Ingelheim, Aerocrine, Teva, Sanofi, Birk NPC as. MG: No COIs related to this work. IP: In the last 5 years IDP has received speaker’s honoraria for speaking at sponsored meetings from Astra Zeneca, Boehringer Ingelheim, Aerocrine, Almirall, Novartis, Teva, Chiesi, Sanofi/Regeneron, Menarini and GSK and payments for organising educational events from AZ, GSK, Sanofi/Regeneron and Teva. He has received honoraria for attending advisory panels with Genentech, Sanofi/ Regeneron, Astra Zeneca, Boehringer Ingelheim, GSK, Novartis, Teva, Merck, Circassia, Chiesi and Knopp and payments to support FDA approval meetings from GSK. He has received sponsorship to attend international scientific meetings from Boehringer Ingelheim, GSK, AstraZeneca, Teva and Chiesi. He has received a grant from Chiesi to support a phase 2 clinical trial in Oxford. DAA: Has received honoraria as grants/contracts from Sociedad Española de Alergología e Inmunología Clínica (SEAIC), as consulting fees from ALK-Abelló, AstraZeneca, Chiesi and Gebro, as speaker from AstraZeneca, Chiesi, Gebro, GSK, Leti Pharma, Mundipharma, Novartis, Roxall, Sanofi. AS: GSK support for an asthma biologic clinical trial 2021-ongoing. PB: Has received honoraria for presentations and consultancy fees from AstraZeneca, Boehringer Ingelheim, Chiesi, ELPEN, GSK, Menarini, Novartis, Sanofi, and Gilead. AB: Takeda, Novartis, Viatris, ALK, Zentiva, MERCK, Stallergenes Greer, Ewopharma, Astra Zeneca, Chiesi, S&D Pharma, Mundipharma, Berlin Chemie. WB: GlaxoSmithKline, Sanofi, Regeneron. JK: Grants and/or personal fees from ALK, Chiesi, GSK, Novartis, AstraZeneca, Sanofi, Boerhinger, Teva, Viatris, Stallergen, Abbot, all outside the submitted work. SL: Honorarium AstraZeneka, GSK, Chiesi Hellas, Sanofi, Elpen, Menarini, Guidoti. MVM: No COIs related to this work. PP: ALK, AstraZeneca, Stallergenes. HP: No COIs related to this work. AS: Reports lecture fees and/or consultancies from AstraZeneca, Chiesi, B.I., GSK, Merck, Novartis, Zambon, Sanofi. HS: No COIs related to this work. IS: No COIs related to this work. BT: No COIs related to this work. MKV: GlaxoSmithKline, AstraZeneca. Diego Conti: No COIs related to this work. WF: The department of Otorhinolaryngology of the Amsterdam University Medical centre, location AMC received grants for research in Rhinology from: ALK, AllergyTherapeutics, Novartis, EU, GSK, MYLAN, Sanofi-Aventis, and Zon-MW; personal COIs: for consultation and/or speaker fees from Dianosic, GSK, Novartis and Sanofi-Aventis/Regeneron. SL: Advisory Board Sanof-Aventis, GSK and Leo-Pharma. Honoraria by DBV Technologies, Allergopharma, Leti, Nutricia, Sanofi-Aventis. GKS: Honoraria for articles, speaker and advisory boards: ALK, AstraZeneca, Capnia, Church & Dwight, Circassia, Noucor, GSK, Meda/Mylan/Viatris, Merck, Sanofi- Regeneron, Stallergenes. Scientific Chief Editor, Rhinology Section, Frontiers in Allergy. Board Member, Lead for Allergic Rhinitis, EUFOREA. Chair of Data Monitoring Board for Paediatric AR trials of HDM SLIT. EVS: No COIs related to this work. PH: Recipient of research grants, honoraria and/or lecture fees of Sanofi, Regeneron, Viatris, GSK, and Novartis. LB: No COIs related to this work.

Allergen specific immunotherapy (AIT) is the only causal therapeutic option for allergic airway diseases including asthma and allergic rhinitis. AIT has been shown to restore the allergen immune tolerance, can modify both the early and late-onset allergen-specific airway hyperreactivity, helps to achieve disease control/remission and prevents new sensitisations. Recent real life data on long-term effectiveness of house dust mite (HDM) AIT in a large group of patients with HDM-driven asthma further underscored its unique therapeutic potential as well as confirmed previous data with pollen AIT. More widespread use of this causal treatment in select patient populations should further move this promising therapeutic field. In this mini-review, we discuss updates on new insights based on real world patient data., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Data on the immune response to SARS-CoV-2 in kidney transplant recipients are scarce. Thus, we conducted a single-center observational study to assess the anti-SARS-CoV-2 IgG seroprevalence in outpatient kidney transplant recipients (KTR; n = 1037) and healthcare workers (HCW; n = 512) during the second wave of the COVID-19 pandemic in fall 2020 and evaluated the clinical variables affecting antibody levels. Antibodies against S1 and S2 subunit of SARS-CoV-2 were evaluated using immunochemiluminescent assay (cut off 9.5 AU/ml, sensitivity of 91.2% and specificity of 90.2%). Anti-SARS-CoV-2 IgG seroprevalence was lower in KTR than in HCW (7% vs. 11.9%, p = .001). Kidney transplant recipients with SARS-CoV-2 infection were younger (p = .001) and received CNI-based immunosuppression more frequently (p = .029) than seronegative KTR. Anti-SARS-CoV-2 IgG positive symptomatic KTR had a higher BMI (p = .04) than asymptomatic KTR. Interestingly, anti-SARS-CoV-2 IgG levels were higher in KTR than in HCW (median 31 AU/ml, IQR 17-84 vs. median 15 AU/ml, IQR 11-39, p < .001). The presence of moderate to severe symptoms in KTR was found to be the only independent factor affecting IgG levels (Beta coefficient = 41.99, 95% CI 9.92-74.06, p = .011) in the multivariable model. In conclusion, KTR exhibit a well-preserved symptom-dependent humoral response to SARS-CoV-2 infection., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Steroid avoidance in immunosuppression in kidney transplantation offers several metabolic advantages, however it is associated with higher early acute rejection rate. Cellular and molecular mechanisms of this phenomenon remain poorly understood., Methods: In this single center observational study, low-risk kidney transplant recipients randomized into large multicenter prospective ADVANCE trial with steroid avoidance/early withdrawal and center standard of care treated patients were monitored for 12months. The expressions of 28 transcripts, associated with alloimmune response and operational tolerance, were evaluated in the peripheral blood using RT-qPCR at 0, 7, 14, 90 and 365 postoperative days (POD) and in the protocol graft biopsy at 3months while lymphocyte subpopulations were analyzed by flow-cytometry within the follow-up., Results: Both steroid avoidance and withdrawal regimens were associated with significantly higher granzyme B (GZMB) transcript at POD 14 and perforin 1 (PRF1) transcript at POD 7. The higher interleukin 2 (IL-2) expression at POD 7 was detected only in the steroid avoidance group. Initial steroids decreased the expression SH2D1B transcript at POD14 and there were no further differences in other operational tolerance transcripts among groups. The statistically significant decrease in absolute numbers of peripheral NK cells in the first 14days was observed in the standard of care group only. There were no differences in analyzed intrarenal transcripts in 3-month biopsies among groups., Conclusions: The enhanced expression of some of Th1 associated transcripts and limited effects on NK cells of steroid avoidance immunosuppression suggest higher susceptibility for early acute rejection., (Copyright © 2017. Published by Elsevier B.V.)

Background: Our retrospective study included a cohort of 47 patients who underwent living donor kidney transplantation.The pre-transplant frequencies of donor-specific Interferon-gamma (IFN-γ) producing cells were define dusing enzyme-linked immunosorbent spot (ELISpot) assay and correlated with incidence of acute cellular(ACR), antibody-mediated rejection (AMR) and kidney graft survival up to one year after transplantation., Results: We found a statistically significant correlation between the frequencies of IFN-γ-producing cells and the number of mismatches in HLA antigens between patients and their respective donors – for Class I – A and B (r = 0.399, p b 0.01) and for Class I and Class II antigens – A, B and DR (r = 0.409, p b 0.01). No significant relationship was observed between the numbers of IFN-γ-secreting cells and incidence of acute rejection (neither ACR, nor AMR). However, there was a trend of elevated frequencies of IFN-γ-producing cells in patients who developed ACR or AMR in comparison with kidney recipients free of rejection (91 ± 82 and 114 ± 75 vs. 72 ± 70/5 × 10(4) peripheral blood mononuclear cells respectively). Patients with concurrent acute cellular and antibody-mediated rejection had also higher numbers of IFN-γ-producing memory/effector cells compared to patients with cellular rejection only., Conclusion: Pre-transplant determination of the numbers of IFN-γ-producing donor-specific memory cells using the ELISpot technique may provide clinically relevant results when evaluating the risk of development of acute cellular and antibody-mediated rejection. These frequencies are influenced by the degree of HLA mismatching between patients and their respective kidney donors.

Background: Grasses belong to major sources of inhaled allergens. The knowledge of particular molecules responsible for hypersensitivity is of crucial importance for better understanding of individual differences among single allergic subjects and allergic populations living in various world-areas., Methods: Specific-IgE-antibodies against Phl p 1, Phl p 5, Phl p 7, Phl p 12 were detected in a group of 130 Phleum-allergic-subjects (82 children, 48 adults)., Results: Phl p 1 antibodies were detected in most pediatric and adult patients, however, the children were associated with higher RAST classes more often. Anti-Phl p 5-antibodies were found more frequently in adults. An increase was observed in the number of pediatric patients reacting to Phl p 7 and Phl p 12. There were no differences in concentrations of specific-IgE against Phl p 5, Phl p 7 and Phl p 12 depending on age. Almost 10% of allergic children produced antibodies directed exclusively against minor allergens or did not produce specific-IgE-antibodies against tested molecules. Part of the patients reacted to profilin and calcium-binding protein originating from only one source (Phl p 12/Bet v 2 and Phl p 7/Bet v 4)., Conclusions: Antibodies against Phl p 1 and Phl p 5 can be used as a marker of allergy to grasses in adult patients. Children reacted exclusively to minor allergens more frequently than adults. Prolonged allergen exposure is evidently necessary to induce sensitization to Phl p 5. A high level of homology between profilins and calcium-binding proteins enables only one allergen to be used for diagnostic purposes but a possibility of a reaction to species-bound epitopes should be taken into account.

Unlabelled: Our retrospective study was aimed to assess the relevance of pre- and post-transplant measurements of serum concentrations of the soluble CD30 molecule (soluble CD30, sCD30) and the cytokine Hepatocyte growth factor (HGF) for prediction of the risk for development of antibody-mediated rejection (AMR) in kidney transplant patients. Evaluation of sCD30, HGF levels and the presence of HLA-specific antibodies in a cohort of 205 patients was performed before, 2weeks and 6months after transplantation. Patients were followed up for kidney graft function and survival for two years. We found a tendency of higher incidence of AMR in retransplanted patients with elevated pre-transplant sCD30 (≥100U/ml) (p=0.051), however no such correlation was observed in first-transplant patients. Kidney recipients with simultaneously high sCD30 and HLA-specific antibodies (sCD30+/Ab+) before transplantation had significantly lower AMR-free survival compared to the other patient groups (p<0.001). HGF concentrations were not associated with the incidence of AMR at any time point of measurement, nevertheless, the combined analysis HGF and sCD30 showed increased incidence of AMR in recipients with elevated pretransplant sCD30 and low HGF levels., Conclusion: the predictive value of pretransplant sCD30 for the development of antibody-mediated rejection after transplantation is significantly potentiated by the co-presence of HLA specific antibodies. The role of HGF as a rejection-protective factor in patients with high pretransplant HGF levels would need further investigation., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: The aim of our study is to investigate correlations of T(H)1/T(H)2 cytokine gene polymorphisms and bronchoalveolar lavage fluid (BALF) cytokine values in interstitial lung diseases (ILD)., Methods: In 16 sarcoidosis, 7 idiopathic pulmonary fibrosis (IPF) and 8 hypersensitivity pneumonitis (HP) patients we evaluated IL-1 alpha, -1R, -1RA, -2, -4, -4R alpha, -6, -10, -12, IFN-gamma, TGF-beta1 and TNF-alpha gene polymorphisms in peripheral blood, and MCP-1,MIP-1 alpha, MIP-1 beta, RANTES, ENA-78, FGF, G-CSF, GM-CSF, IFN-gamma, IL-1 alpha, IL-1RA, IL-1 beta, -2, -4, -5, -6, -8, -10, -17, TNF-alpha, Tpo and VEGF values in BALF., Results: We found higher TNF-alpha values in IL-1R pst 1970 TT homozygotes regardless of diagnosis (p=0.0126). In the sarcoidosis group IL-4R alpha(+1902)AA and IL-10(-1082)G allele correlated with higher BALF ENA-78 levels (p=0.0258, p=0.0230). In the HP group the IL-6(-174)CG and IL-6(nt565)AG correlated with higher ENA-78 BALF levels (p=0.0253). In the IPF group the IL-1 beta +3962 CC homozygotes had lower IL-1RA BALF values (p=0.046). BALF chemokine values did not differ between ILD subgroups, except for IL-8, which was higher in stage III sarcoidosis patients compared to stage I., Conclusion: Our results show a probable influence of gene polymorphisms, namely IL-4R alpha and IL-10 on ENA-78 BALF levels in sarcoidosis, IL-6 on ENA-78 BALF levels in HP and IL-1-beta on IL-1RA BALF values in the IPF group. The TNF-alpha BALF values correlated with IL-1R pst 1970 gene polymorphisms.

Unlabelled: The aim of our retrospective study was to evaluate the clinical significance of measurement of the soluble CD30 (sCD30) molecule for the prediction of antibody-mediated (humoral) rejection (HR). Sixty-two kidney transplant recipients (thirty-one C4d-positive and thirty-one C4d-negative patients) were included into the study. Soluble CD30 levels were evaluated before transplantation and during periods of graft function deterioration. The median concentrations of the sCD30 molecule were identical in C4d-positive and C4d-negative patients before and after transplantation (65.5 vs. 65.0 and 28.2 vs. 36.0 U/ml, respectively). C4d+ patients who developed DSA de novo had a tendency to have higher sCD30 levels before transplantation (80.7+/-53.6 U/ml, n=8) compared with C4d-negative patients (65.0+/-33.4 U/ml, n=15). Soluble CD30 levels were evaluated as positive and negative (>or=100 U/ml and <100 U/ml respectively) and the sensitivity, specificity and accuracy of sCD30 estimation with regard to finding C4d deposits in peritubular capillaries were determined. The sensitivity of sCD30+ testing was generally below 40%, while the specificity of the test, i.e. the likelihood that if sCD30 testing is negative, C4d deposits would be absent, was 82%. C4d+ patients who developed DSA de novo were evaluated separately; the specificity of sCD30 testing for the incidence of HR in this cohort was 86%., Conclusion: We could not confirm in our study that high sCD30 levels (>or=100 U/ml) might be predictive for the incidence of HR. Negative sCD30 values might be however helpful for identifying patients with a low risk for development of DSA and antibody-mediated rejection.

Introduction: Idiopathic pulmonary fibrosis (IPF) is a serious disease with unknown cause and the influence of cytokine gene polymorphisms is presumed in the etiology and pathogenesis of the disease. We used high-resolution computed tomography (HRCT) as a marker of disease stage and progression and compared the alveolar and interstitial score with IL-1, IL-4, IL-12, IL-1RA and IL-4RA cytokine gene polymorphisms., Subjects and Methods: The IPF patients were all Caucasians from the Czech Republic and consisted of 20 females and 10 males, with a mean age of 65 years, range 36-85. The HRCT results were evaluated by an experienced viewer using the interstitial and alveolar score scales, which were based on the IPF HRCT description system from Gay SE, Kazerooni EA, Tows GB, Lynch JP, Gross BH, Cascade PN, et al. [Idiopathic pulmonary fibrosis. Predicting response to therapy and survival. Am J Respir Crit Care Med 1998;157:1063-72]. We evaluated the polymorphisms of cytokine genes utilizing a PCR with sequence-specific primers method., Results: The HRCT alveolar score was more pronounced in IL-4 RA (+1902) AG heterozygotes. The HRCT interstitial score was less severe in the IL-12 (-1188) AA homozygotes. According to progression of the HRCT interstitial score, the CC homozygosity at IL-1 RA (mspa 111100), the AA homozygosity at IL-4 RA (+1902) and CC homozygosity at IL-4(+33) positions were more frequent in patients with stable disease compared to those with progressive disease., Conclusions: We assume from our data that the polymorphisms of IL-4, IL-4RA, IL-1RA and IL-12 genes (genes of cytokines with regulatory activity) might influence the phenotype of IPF as shown by measurable changes in HRCT investigations.

Recent literary data suggest that high pre- and post-transplant serum levels of the soluble CD30 (sCD30) molecule may be a risk factor for acute rejection and worse prognosis of the transplanted kidney. The aim of our study was to correlate the concentrations of sCD30 and the presence of HLA antibodies as defined by flow cytometry and ELISA with the clinical course and graft prognosis after transplantation. One hundred and seventeen kidney transplant patients were included into the study. The incidence of rejection episodes, graft function and graft survival for up to 1 year post-transplant were evaluated. Soluble CD30 levels before transplantation were virtually the same in patients who experienced rejection and in non-rejecting patients. In both patient groups, a significant decrease of sCD30 was detected 2 weeks after transplantation (104.4 U/ml before vs. 37.0 U/ml post-transplant, P < 0.001). However, there was a substantial difference in the level of decrease of sCD30 between rejecting and non-rejecting patients. Patients without rejection had lower sCD30 values (31.2 U/ml post-transplant) compared to patients who experienced rejection episodes (62.9 U/ml), P < 0.04. Multifactorial analysis showed that antibodies to HLA class II antigens and elevated concentrations of sCD30 shortly after transplantation were associated with increased risk for acute rejection in the first post-transplant year. Measurement of soluble CD30 after transplantation, taken into consideration with the presence of HLA class II antibodies, might be helpful for evaluating the potential risk for acute rejection.