Diagnosis of the autoimmune disease type 1 diabetes (T1D) is preceded by the appearance of circulating autoantibodies to pancreatic islets. However, almost nothing is known about events leading to this islet autoimmunity. Previous epidemiological and genetic data have associated viral infections and antiviral type I interferon (IFN) immune response genes with T1D. Here, we first used DNA microarray analysis to identify IFN-β–inducible genes in vitro and then used this set of genes to define an IFN-inducible transcriptional signature in peripheral blood mononuclear cells from a group of active systemic lupus erythematosus patients (n = 25). Using this predefined set of 225 IFN signature genes, we investigated the expression of the signature in cohorts of healthy controls (n = 87), patients with T1D (n = 64), and a large longitudinal birth cohort of children genetically predisposed to T1D (n = 109; 454 microarrayed samples). Expression of the IFN signature was increased in genetically predisposed children before the development of autoantibodies (P = 0.0012) but not in patients with established T1D. Upregulation of IFN-inducible genes was transient, temporally associated with a recent history of upper respiratory tract infections (P = 0.0064), and marked by increased expression of SIGLEC-1 (CD169), a lectin-like receptor expressed on CD14+ monocytes. DNA variation in IFN-inducible genes altered T1D risk (P = 0.007), as exemplified by IFIH1, one of the genes in our IFN signature for which increased expression is a known risk factor for disease. These findings identify transient increased expression of type I IFN genes in preclinical diabetes as a risk factor for autoimmunity in children with a genetic predisposition to T1D.

Objective: To describe the impact of pandemic (H1N1) 2009 influenza (nH1N1) on Indigenous people in the Top End of the Northern Territory at community, hospital and intensive care unit (ICU) levels. Design, setting and participants: We analysed influenza notifications for the Top End from 1 June to 31 August 2009, as well as data on patients admitted through Top End emergency departments with an influenza‐like illness. In addition, data on patients with nH1N1 who were admitted to Royal Darwin Hospital (RDH) and the RDH ICU were prospectively collected and analysed. Main outcome measures: Age‐adjusted notification rates for nH1N1 cases, Top End hospital admission rates for patients with nH1N1 and RDH ICU admission rates for patients with nH1N1, stratified by Indigenous status. Results: There were 918 nH1N1 notifications during the study period. The age‐adjusted hospital admission rate for nH1N1 was 82 per 100 000 (95% CI, 68–95) estimated resident population (ERP) overall, with a markedly higher rate in the Indigenous population compared with the non‐Indigenous population (269 per 100 000 versus 29 per 100 000 ERP; adjusted incidence rate ratio, 12 [95% CI, 7.8–18]). Independent predictors of ICU admission compared with hospitalisation were hypoxia (adjusted odds ratio [aOR], 4.5; CI, 1.5–13.1) and chest x‐ray infiltrates (aOR, 4.3; CI, 1.5–12.6) on hospital admission. Conclusions: Pandemic (H1N1) 2009 influenza had a disproportionate impact on Indigenous Australians in the Top End, with hospitalisation rates higher than those reported elsewhere in Australia and overseas. These findings have implications for planning hospital and ICU capacity during an influenza pandemic in regions with large Indigenous populations. They also confirm the need to improve health and living circumstances and to prioritise vaccination in this population.

ABO-incompatible (ABOi) kidney transplantation is an established therapy, though its implementation to date has been in part limited

Antineutrophil cytoplasm antibody (ANCA)–associated vasculitis (AAV) commonly results in glomerulonephritis, in which neutrophils and monocytes have important roles. The heterodimer calprotectin (S100A8/S100A9, mrp8/14) is a Toll-like receptor-4 ligand found in neutrophils and monocytes and is elevated in inflammatory conditions. By immunohistochemistry of renal biopsies, patients with focal or crescentic glomerular lesions were found to have the highest expression of calprotectin and those with sclerotic the least. Serum levels of calprotectin as measured by ELISA were elevated in patients with active AAV and the levels decreased but did not normalize during remission, suggesting subclinical inflammation. Calprotectin levels in patients with limited systemic disease increased following treatment withdrawal and were significantly elevated in patients who relapsed compared with those who did not. As assessed by flow cytometry, patients with AAV had higher monocyte and neutrophil cell surface calprotectin expression than healthy controls, but this was not associated with augmented mRNA expression in CD14+ monocytes or CD16+ neutrophils. Thus, serum calprotectin is a potential disease biomarker in patients with AAV, and may have a role in disease pathogenesis.