Genetic polymorphism related to monocyte-macrophage function is associated with graft-versus-host disease

Despite detailed human leukocyte antigen (HLA) matching and modern immunosuppressive therapy, severe graft-versus-host disease (GvHD) remains a major hurdle for successful allogeneic hematopoietic stem cell transplantation (HSCT). As the genetic diversity in GvHD complicates the systematic discovery of associated variants across populations, we studied 122 GvHD-associated single nucleotide polymorphisms (SNPs) in 492 HLA-matched sibling HSCT donor-recipient pairs from Finland and Spain. The association between these candidate SNPs and grade III-IV acute GvHD and extensive chronic GvHD was assessed. The functional effects of the variants were determined using expression and cytokine quantitative trait loci (QTL) database analyses. Clear heterogeneity was observed in the associated markers between the two populations. Interestingly, the majority of markers, such as those annotated to IL1, IL23R, TLR9, TNF, and NOD2 genes, are related to the immunological response by monocytes-macrophages to microbes, a step that precedes GvHD as a result of intestinal lesions. Furthermore, cytokine QTL analysis showed that the GvHD-associated markers regulate IL1 beta, IFN gamma, and IL6 responses. These results support a crucial role for the anti-microbial response in GvHD risk. Furthermore, despite apparent heterogeneity in the genetic markers associated with GvHD, it was possible to identify a biological pathway shared by most markers in both populations.Peer reviewe

Indoor microbiota in severely moisture damaged homes and the impact of interventions

Background: The limited understanding of microbial characteristics in moisture-damaged buildings impedes efforts to clarify which adverse health effects in the occupants are associated with the damage and to develop effective building intervention strategies. The objectives of this current study were (i) to characterize fungal and bacterial microbiota in house dust of severely moisture-damaged residences, (ii) to identify microbial taxa associated with moisture damage renovations, and (iii) to test whether the associations between the identified taxa and moisture damage are replicable in another cohort of homes. We applied bacterial 16S rRNA gene and fungal ITS amplicon sequencing complemented with quantitative PCR and chemical-analytical approaches to samples of house dust, and also performed traditional cultivation of bacteria and fungi from building material samples. Results: Active microbial growth on building materials had significant though small influence on the house dust bacterial and fungal communities. Moisture damage interventions-including actual renovation of damaged homes and cases where families moved to another home-had only a subtle effect on bacterial community structure, seen as shifts in abundance weighted bacterial profiles after intervention. While bacterial and fungal species richness were reduced in homes that were renovated, they were not reduced for families that moved houses. Using different discriminant analysis tools, we were able identify taxa that were significantly reduced in relative abundance during renovation of moisture damage. For bacteria, the majority of candidates belonged to different families within the Actinomycetales order. Results for fungi were overall less consistent. A replication study in approximately 400 homes highlighted some of the identified taxa, confirming associations with observations of moisture damage and mold. Conclusions: The present study is one of the first studies to analyze changes in microbiota due to moisture damage interventions using high-throughput sequencing. Our results suggest that effects of moisture damage and moisture damage interventions may appear as changes in the abundance of individual, less common, and especially bacterial taxa, rather than in overall community structure.Peer reviewe

Use of host- and bacteria-derived salivary markers in detection of periodontitis: A cumulative approach

In the present study, we propose a novel diagnostic approach, using 3 different salivary markers, representing periodontal pathogen burden, inflammation, and tissue degradation, for detecting periodontitis. The salivary concentrations of Porphyromonas gingivalis, interleukin-1β, and matrix metalloproteinase-8, available from salivary specimens of 165 subjects (84 subjects with advanced periodontitis and 81 controls), were calculated together to obtain a cumulative risk score (CRS). In the calculation of CRS, the concentrations of each marker were divided into tertiles, and cumulative sub-score per each subject were calculated by the multiplication of the tertile values. Three CRS groups, indicating the lowest, medium, or highest risk, were formed with the cumulative sub-scores. Logistic regression analysis and ROC curves were performed to study the association of CRS with periodontitis. The results indicate that CRS, calculated from the 3 salivary biomarkers, is associated with advanced periodontitis more strongly than any of the markers individually. CRS offers a novel, non-invasive model for advanced periodontitis risk categorization that is especially useful in large population surveys where a periodontal examination is not feasible