Hyper-IgG4 disease: report and characterisation of a new disease

BACKGROUND: We highlight a chronic inflammatory disease we call 'hyper-IgG4 disease', which has many synonyms depending on the organ involved, the country of origin and the year of the report. It is characterized histologically by a lymphoplasmacytic inflammation with IgG4-positive cells and exuberant fibrosis, which leaves dense fibrosis on resolution. A typical example is idiopathic retroperitoneal fibrosis, but the initial report in 2001 was of sclerosing pancreatitis. METHODS: We report an index case with fever and severe systemic disease. We have also reviewed the histology of 11 further patients with idiopathic retroperitoneal fibrosis for evidence of IgG4-expressing plasma cells, and examined a wide range of other inflammatory conditions and fibrotic diseases as organ-specific controls. We have reviewed the published literature for disease associations with idiopathic, systemic fibrosing conditions and the synonyms: pseudotumour, myofibroblastic tumour, plasma cell granuloma, systemic fibrosis, xanthofibrogranulomatosis, and multifocal fibrosclerosis. RESULTS: Histology from all 12 patients showed, to varying degrees, fibrosis, intense inflammatory cell infiltration with lymphocytes, plasma cells, scattered neutrophils, and sometimes eosinophilic aggregates, with venulitis and obliterative arteritis. The majority of lymphocytes were T cells that expressed CD8 and CD4, with scattered B-cell-rich small lymphoid follicles. In all cases, there was a significant increase in IgG4-positive plasma cells compared with controls. In two cases, biopsies before and after steroid treatment were available, and only scattered plasma cells were seen after treatment, none of them expressing IgG4. Review of the literature shows that although pathology commonly appears confined to one organ, patients can have systemic symptoms and fever. In the active period, there is an acute phase response with a high serum concentration of IgG, and during this phase, there is a rapid clinical response to glucocorticoid steroid treatment. CONCLUSION: We believe that hyper-IgG4 disease is an important condition to recognise, as the diagnosis can be readily verified and the outcome with treatment is very good

Mitochondrial plasticity in brachiopod (Liothyrella spp.) smooth adductor muscle as a result of season and latitude

Habitat temperature and mitochondrial volume density (Vv(mt,mf)) are negatively correlated in fishes, while seasonal acclimatization may increase Vv(mt,mf) or the surface density of the mitochondrial cristae (Sv(im,mt)). The effect of temperature on invertebrate mitochondria is essentially unknown. A comparison of two articulate brachiopod species, Liothyrella uva collected from Rothera Station, Antarctica in summer 2007, and Liothyrella neozelanica collected from Fiordland, New Zealand in winter 2007 and summer 2008, revealed a higher Vv(mt,mf) in the Antarctic brachiopod. The Sv(im,mt) was, however, significantly lower, indicating the Antarctic brachiopods have more, less reactive mitochondria. L. uva, from the colder environment, had larger adductor muscles in both absolute and relative terms than the temperate L. neozelanica. Furthermore, a seasonal comparison (winter vs. summer) in L. neozelanica showed that the absolute and relative size of the adductor increased in winter, Vv(mt,mf) was unchanged, and Sv(im,mt) was significantly increased. Thus, seasonal acclimatization to the cold resulted in the same number of more reactive mitochondria. L. neozelanica was clearly able to adapt to seasonal changes using a different mechanism, i.e. primarily through regulation of cristae surface area as opposed to mitochondrial volume density. Furthermore, given the evolutionary age of these living fossils (i.e. approximately 550 million years), this suggests that mitochondrial plasticity has roots extending far back into evolutionary history

Mitochondrial Acclimation Capacities to Ocean Warming and Acidification Are Limited in the Antarctic Nototheniid Fish, Notothenia rossii and Lepidonotothen squamifrons

Antarctic notothenioid fish are characterized by their evolutionary adaptation to the cold, thermostable Southern Ocean, which is associated with unique physiological adaptations to withstand the cold and reduce energetic requirements but also entails limited compensation capacities to environmental change. This study compares the capacities of mitochondrial acclimation to ocean warming and acidification between the Antarctic nototheniid Notothenia rossii and the sub-Antarctic Lepidonotothen squamifrons, which share a similar ecology, but different habitat temperatures. After acclimation of L. squamifrons to 9°C and N. rossii to 7°C (normocapnic/hypercapnic, 0.2 kPa CO2/2000 ppm CO2) for 4-6 weeks, we compared the capacities of their mitochondrial respiratory complexes I (CI) and II (CII), their P/O ratios (phosphorylation efficiency), proton leak capacities and mitochondrial membrane fatty acid compositions. Our results reveal reduced CII respiration rates in warm-acclimated L. squamifrons and cold hypercapnia-acclimated N. rossii. Generally, L. squamifrons displayed a greater ability to increase CI contribution during acute warming and after warm-acclimation than N. rossii. Membrane unsaturation was not altered by warm or hypercapnia-acclimation in both species, but membrane fatty acids of warm-acclimated L. squamifrons were less saturated than in warm normocapnia-/hypercapnia-acclimated N. rossii. Proton leak capacities were not affected by warm or hypercapnia-acclimation of N. rossii. We conclude that an acclimatory response of mitochondrial capacities may include higher thermal plasticity of CI supported by enhanced utilization of anaplerotic substrates (via oxidative decarboxylation reactions) feeding into the citrate cycle. L. squamifrons possesses higher relative CI plasticities than N. rossii, which may facilitate the usage of energy efficient NADH-related substrates under conditions of elevated energy demand, possibly induced by ocean warming and acidification. The observed adjustments of electron transport system complexes with a higher flux through CI under warming and acidification suggest a metabolic acclimation potential of the sub-Antarctic L. squamifrons, but only limited acclimation capacities for N. rossii