Effects of temperature on viral load, inclusion body formation, and host response in Pacific Herring with viral erythrocytic necrosis (VEN).

OBJECTIVE: The primary objective of this study was to determine the effects of temperature on viral erythrocytic necrosis (VEN) progression under controlled conditions. Secondarily, this study was intended to evaluate the combined effects of temperature and VEN on the Pacific Herring Clupea palasii transcriptome. METHODS: The effects of temperature on VEN progression were assessed by waterborne exposure of laboratory-reared, specific-pathogen-free Pacific Herring to tissues homogenates containing erythrocytic necrosis virus (ENV) at 6.9, 9.0, or 13.5°C. RESULT: Exposure of Pacific Herring to ENV resulted in the establishment of infections characterized by high infection prevalence (89%; 40/45) and mean viral loads (5.5 log10 [gene copies/µg genomic DNA]) in kidney tissues at 44 days postexposure. Mean viral loads were significantly higher in fish from the ambient (mean = 9.0°C) and warm (mean = 13.5°C) treatments (6.1-6.2 log10 [gene copies/total genomic DNA]) than in fish from the cool (mean = 6.9°C) treatment (4.3 log10 [gene copies/µg genomic DNA]). Similarly, the peak proportion of diseased fish was directly related to temperature, with cytoplasmic inclusion bodies detected in 21% of fish from the cool treatment, 52% of fish from the ambient treatment, and 60% of fish from the warm treatment. The mean VEN load in each fish (enumerated as the percentage of erythrocytes with cytoplasmic inclusions) at 44 days postexposure increased with temperature from 15% in the cool treatment to 36% in the ambient treatment and 32% in the warm treatment. Transcriptional analysis indicated that the number of differentially expressed genes among ENV-exposed Pacific Herring increased with temperature, time postexposure, and viral load. Correlation network analysis of transcriptomic data showed robust activation of interferon and viral immune responses in the hepatic tissue of infected individuals independent of other experimental variables. CONCLUSION: Results from this controlled laboratory study, combined with previous observations of natural epizootics in wild populations, support the conclusion that temperature is an important disease cofactor for VEN in Pacific Herring.

Serology in autoimmune pancreatitis.

Autoimmune pancreatitis (AIP) is the pancreatic manifestation of a systemic immune-driven, inflammatory process that can involve organs such as the bile duct, salivary glands and lymph nodes, in addition to the pancreas. Many of the presenting signs and symptoms of AIP, including painless jaundice, weight loss and mild epigastric pain, are characteristic of pancreatic adenocarcinoma; thus, obtaining an accurate diagnosis to avoid unnecessary surgery is imperative. AIP responds very well to steroid treatment, although it may recur in up to 20% to 40% of cases. The diagnostic criteria for AIP are histological, radiographic, clinical and laboratory-based in nature. Although no international consensus on diagnostic criteria has yet been made, some of the diagnostic features of AIP include elevated gamma globulin, immunoglobulin, and, in particular, immunoglobulin G4 fraction (IgG4). The search for a distinct serological marker of AIP has included antibodies to a wide range of antigenic stimuli. To date, there have been studies of AIP and antibodies to lactoferrin, carbonic anhydrase isoforms II and IV, pancreatic secretory trypsin inhibitor (PSTI or SPINK) as well as to less sensitive or specific markers of autoimmunity, such as antinuclear antibody and rheumatoid factor. Although there are some preliminary strengths of association with PSTI antibodies, none of these biomarkers appears to be sensitive or specific enough to serve as distinctive evidence of AIP. At the current time, elevations of IgG4 to greater than 280 mg/dL remain the most reliable and reproducible indicator that a patient has AIP.