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Aspergillus fumigatus can cause different clinical manifestations/phenotypes in lung transplant (LTx) recipients and patients with chronic respiratory diseases. It can also precipitate chronic lung allograft dysfunction (CLAD) in LTx recipients. Many host factors have been linked with the severity of A. fumigatus infection, but little is known about the contribution of different A. fumigatus strains to the development of different phenotypes and CLAD. We used multi-locus microsatellite typing (MLMT) to determine if there is a relationship between strain (i.e., genotype) and phenotype in 60 patients post LTx or with chronic respiratory disease across two time periods (1 November 2006–31 March 2009 and 1 November 2015–30 June 2017). The MLMT (STRAf) assay was highly discriminatory (Simpson’s diversity index of 0.9819–0.9942) with no dominant strain detected. No specific genotype–phenotype link was detected, but several clusters and related strains were associated with invasive aspergillosis (IA) and colonisation in the absence of CLAD. Host factors were linked to clinical phenotypes, with prior lymphopenia significantly more common in IA cases as compared with A. fumigatus-colonised patients (12/16 [75%] vs. 13/36 [36.1%]; p = 0.01), and prior Staphylococcus aureus infection was a significant risk factor for the development of IA (odds ratio 13.8; 95% confidence interval [2.01–279.23]). A trend toward a greater incidence of CMV reactivation post-A. fumigatus isolation was observed (0 vs. 5; p = 0.06) in LTx recipients. Further research is required to determine the pathogenicity and immunogenicity of specific A. fumigatus strains.

Many distinct regions of 3p show frequent allelic losses in a wide range of tumour types. Previously, the BLU candidate tumour suppressor gene (TSG) encoded by a gene-rich critical deleted region in 3p21.3 was found to be inactivated rarely in lung cancer, although expression was downregulated in a subset of lung tumour cell lines. To elucidate the role of BLU in tumorigenesis, we analysed BLU promoter methylation status in tumour cell lines and detected promoter region hypermethylation in 39% lung, 42% breast, 50% kidney, 86% neuroblastoma and 80% nasopharyngeal (NPC) tumour cell lines. Methylation of the BLU promoter region correlated with the downregulation of BLU transcript expression in tumour cell lines. Expression was recovered in tumour cell lines treated with 5-aza 2-deoxycytidine. Exogenous expression of BLU in neuroblastoma (SK-N-SH) and NSCLC (NCI-H1299) resulted in reduced colony formation efficiency, in vitro . Furthermore, methylation of the BLU promoter region was detected in primary sporadic SCLC (14%), NSCLC (19%) and neuroblastoma (41%). As frequent methylation of the RASSF1A 3p21.3 TSG has also been reported in these tumour types, we investigated whether BLU and RASSF1A methylation were independent or related events. No correlation was found between hypermethylation of RASSF1A and BLU promoter region CpG islands in SCLC or neuroblastoma. However, there was association between RASSF1A and BLU methylation in NSCLC ( P =0.0031). Our data suggest that in SCLC and neuroblastoma, RASSF1A and BLU methylations are unrelated events and not a manifestation of a regional alteration in epigenetic status, while in NSCLC there may be a regional methylation effect. Together, these data suggest a significant role for epigenetic inactivation of BLU in the pathogenesis of common human cancers and that methylation inactivation of BLU occurs independent of RASSF1A in SCLC and neuroblastoma tumours.

Aspergillus fumigatus can cause different clinical manifestations/phenotypes in lung transplant (LTx) recipients and patients with chronic respiratory diseases. It can also precipitate chronic lung allograft dysfunction (CLAD) in LTx recipients. Many host factors have been linked with the severity of A. fumigatus infection, but little is known about the contribution of different A. fumigatus strains to the development of different phenotypes and CLAD. We used multi-locus microsatellite typing (MLMT) to determine if there is a relationship between strain (i.e., genotype) and phenotype in 60 patients post LTx or with chronic respiratory disease across two time periods (1 November 2006–31 March 2009 and 1 November 2015–30 June 2017). The MLMT (STRAf) assay was highly discriminatory (Simpson’s diversity index of 0.9819–0.9942) with no dominant strain detected. No specific genotype–phenotype link was detected, but several clusters and related strains were associated with invasive aspergillosis (IA) and colonisation in the absence of CLAD. Host factors were linked to clinical phenotypes, with prior lymphopenia significantly more common in IA cases as compared with A. fumigatus-colonised patients (12/16 [75%] vs. 13/36 [36.1%]; p = 0.01), and prior Staphylococcus aureus infection was a significant risk factor for the development of IA (odds ratio 13.8; 95% confidence interval [2.01–279.23]). A trend toward a greater incidence of CMV reactivation post-A. fumigatus isolation was observed (0 vs. 5; p = 0.06) in LTx recipients. Further research is required to determine the pathogenicity and immunogenicity of specific A. fumigatus strains.

Objectives Infections are a major cause of mortality after allogeneic haemopoietic stem cell transplantation (alloHSCT), and immune recovery is necessary for prevention. Novel transplant procedures have changed the epidemiology of infections but contemporary data on functional immune recovery are limited. In this pilot study, we aimed to measure immune recovery in the current era of alloHSCT. Methods Twenty, 13, 11, 9 and 9 alloHSCT recipients had blood collected at baseline (time of conditioning) and 3‐, 6‐, 9‐, and 12‐months post‐alloHSCT, respectively. Clinical data were collected, and immune recovery was measured using immunophenotyping, lymphocyte proliferation, cytokine analysis and antibody isotyping. Results Median absolute T‐ and B‐cell counts were below normal from baseline until 9‐ to 12‐months post‐alloHSCT. Median absolute CD4+ T‐cell counts recovered at 12‐months post‐alloHSCT. Positive proliferative responses to Aspergillus, cytomegalovirus (CMV), Epstein‐Barr virus (EBV), influenza and tetanus antigens were detected from 9 months. IL‐6 was the most abundant cytokine in cell cultures. In cultures stimulated with CMV, EBV, influenza and tetanus peptides, the CD4+ T‐cell count correlated with IL‐1β (P = 0.045) and CD8+ T‐cell count with IFNγ (P = 0.013) and IL‐1β (P = 0.012). The NK‐cell count correlated with IL‐1β (P = 0.02) and IL‐17a (P = 0.03). Median serum levels of IgG1, IgG2 and IgG3 were normal while IgG4 and IgA were below normal range throughout follow‐up. Conclusions This pilot study demonstrates that immune recovery can be measured using CD4+ T‐cell counts, in vitro antigen stimulation and selected cytokines (IFNγ, IL‐1β, IL‐4, IL‐6, IL‐17, IL‐21, IL‐31) in alloHSCT recipients. While larger studies are required, monitoring immune recovery may have utility in predicting infection risk post‐alloHSCT. Infection is a major problem in allogeneic stem cell transplant recipients. Immune‐based risk stratification is required to guide the duration of anti‐microbial prophylaxis administration and timing of re‐vaccination. This proof of concept study demonstrates that immune recovery can be measured using CD4+ T‐cell counts, pathogen specific immune responses and selected cytokines (IFN‐gamma, IL‐1‐beta, IL‐4, IL‐6, IL‐17, IL‐21, IL‐31). Immune parameters measured may have utility in infection‐risk stratification and provides a framework for larger cohort studies.

The ACCC launched legal action on Wednesday against Mr [Richard Pratt]'s privately-owned Visy Group companies - Visy Industries Pty Ltd, Visy Industries Australia Pty Ltd and Visy Board Pty Ltd - following a year-long investigation into the $1.8 billion packaging industry.