Variability of antigenicity/allergenicity in different strains of Alternaria alternata

Biochemical and immunological properties were studied in crude mould extracts from 10 different strains of Alternaria alternata. The mould strains were grown on completely synthetic medium and harvested under identical conditions. The biochemical and immunological analyses (protein content, carbohydrate content, IEF, RAST-inhibition, CIE/CRIE and the content of a major allergen) showed significant variations between the individual strains of A. alternata. 32 antigens were identified in the CIE pattern of A. alternata and 19 different allergens were identified in CRIE analysis (1 major, 7 intermediate and 6 minor allergens). There was a significant variation in the content of the major A. alternata allergen (Ag-8, partially identical to Alt-I) between the different individual strains. Furthermore, a considerable variation in the content of Ag-8 was observed for a specific strain cultivated at different occasions under identical cultivation conditions during a time period of 3 years.     

Chemokines and soluble adhesion molecules in renal transplant recipients with cytomegalovirus infection

Cytomegalovirus (CMV) infection is associated with leucocyte infiltration in various organs, which supports a role for chemokines and adhesion molecules in the pathogenesis of CMV infection. In a prospectively conducted study of renal transplant recipients, 10 patients with CMV disease, five patients with asymptomatic CMV infection and 10 patients who did not have any CMV infection were included. During CMV infection, and in particular during CMV disease, plasma levels of the chemokines IL-8, macrophage inflammatory protein-1alpha (MIP-1alpha) and monocyte chemotactic protein-1 (MCP-1) and the soluble adhesion molecules vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and L-selectin increased and were positively correlated with the degree of CMV pp65 antigenaemia. Furthermore, a decrease in plasma levels of these chemokines and adhesion molecules was observed following ganciclovir therapy in the patients with CMV disease. This could suggest a role for these molecules in the pathogenesis of CMV infection.     

Impact of Systemic Inflammation on the Progression of Gestational Diabetes Mellitus

With increasing rates of obesity and new diagnostic criteria for gestational diabetes mellitus (GDM), the overall prevalence of GDM is increasing worldwide. Women with GDM have an increased risk of maternal and fetal complications during pregnancy as well as long-term risks including higher prevalence of type 2 diabetes mellitus and cardiovascular disease. In recent years, the role of immune activation and inflammation in the pathogenesis of GDM has gained increasing attention. This monograph explores the current state of the literature as regards the expression of markers of inflammation in the maternal circulation, placenta, and adipose tissue of women with GDM.     

Dominant ARL3-related retinitis pigmentosa

Purpose: To clinically and genetically characterise a second family with dominant ARL3-related retinitis pigmentosa due to a specific ARL3 missense variant, p.(Tyr90Cys).

Methods: Clinical examination included optical coherence tomography, electroretinography, and ultra-wide field retinal imaging with autofluorescence. Retrospective data were collected from the registry of inherited retinal diseases at Oslo university hospital. DNA was analysed by whole-exome sequencing and Sanger sequencing. The ARL3 missense variant was visualized in a 3D-protein structure.

Results: The phenotype was non-syndromic retinitis pigmentosa with cataract associated with early onset of decreased central vision and central retinal thinning. Sanger sequencing confirmed the presence of a de novo ARL3 missense variant p.(Tyr90Cys) in the index patient and his affected son. We did not find any other cases with rare ARL3 variants in a cohort of 431 patients with retinitis pigmentosa-like disease. By visualizing Tyr90 in the 3D protein structure, it seems to play an important role in packing of the α/β structure of ADP-ribosylation factor-like 3 (ARL3). When changing Tyr90 to cysteine, we observe a loss of interactions in the core of the α/β structure that is likely to affect folding and stability of ARL3.

Conclusion: Our study confirms that the ARL3 missense variant p.(Tyr90Cys) causes retinitis pigmentosa. In 2016, Strom et al. reported the exact same variant in a mother and two children with RP, labelled ?RP83 in the OMIM database. Now the questionmark can be removed, and ARL3 should be added to the list of genes that may cause non-syndromic dominant retinitis pigmentosa.     

Cytokine responses,microbial aetiology and short‐term outcome in community‐acquired pneumonia

Background

The inflammatory response to community‐acquired pneumonia (CAP) is orchestrated through activation of cytokine networks and the complement system. We examined the association of multiple cytokines and the terminal complement complex (TCC) with microbial aetiology, disease severity and short‐term outcome.

Materials and methods

Plasma levels of 27 cytokines and TCC were analysed in blood samples obtained at hospital admission, clinical stabilization and 6‐week follow‐up from 247 hospitalized adults with CAP. Fourteen mediators were included in final analyses. Adverse short‐term outcome was defined as intensive care unit (ICU) admission and 30‐day mortality.

Results

Cytokine and TCC levels were dynamic in the clinical course of CAP, with highest levels seen at admission for most mediators. Admission levels of cytokines and TCC did not differ between groups of microbial aetiology. High admission levels of IL‐6 (odds ratio [OR] 1.47, 95% confidence interval [CI] 1.18‐1.84, P = .001), IL‐8 (OR 1.79, 95% CI 1.26‐2.55, P = .001) and MIP‐1β (OR 2.28, 95% CI 1.36‐3.81, P = .002) were associated with a CURB‐65 severity score of ≥3, while IL‐6 (OR 1.37, 95% CI 1.07‐1.74, P = .011) and MIP‐1β (OR 1.86, 95% CI 1.03‐3.36, P = .040) were associated with a high risk of an adverse short‐term outcome.

Conclusions

In this CAP cohort, admission levels of IL‐6, IL‐8 and MIP‐1β were associated with disease severity and/or adverse short‐term outcome. Still, for most mediators, only nonsignificant variations in inflammatory responses were observed for groups of microbial aetiology, disease severity and short‐term outcome.     

Common variable immunodeficiency revisited: normal generation of naturally occurring dendritic cells that respond to Toll‐like receptors 7 and 9

Patients with common variable immunodeficiency (CVID) have reduced numbers and frequencies of dendritic cells (DCs) in blood, and there is also evidence for defective activation through Toll‐like receptors (TLRs). Collectively, these observations may point to a primary defect in the generation of functional DCs. Here, we measured frequencies of plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) in peripheral blood of 26 CVID patients and 16 healthy controls. The results show that the patients have reduced absolute counts of both subsets. However, the decreased numbers in peripheral blood were not reflected in reduced frequencies of CD34⁺ pDC progenitors in the bone marrow. Moreover, studies at the single cell level showed that DCs from CVID patients and healthy controls produced similar amounts of interferon‐α or interleukin‐12 and expressed similar levels of activation markers in response to human cytomegalovirus and ligands for TLR‐7 and TLR‐9. The study represents the most thorough functional characterization to date, and the first to assess bone marrow progenitor output, of naturally occurring DCs in CVID. In conclusion, it seems unlikely that CVID is secondary to insufficient production of naturally occurring DCs or a defect in their signalling through TLR‐7 or TLR‐9.