Immunoglobulin A vasculitis associated with inflammatory bowel disease: a retrospective cohort study.

Objective: To describe the baseline characteristics and outcome of a series of patients with inflammatory bowel disease (IBD) and immunoglobulin A vasculitis (IgAV). Method: Patients with biopsy-proven IgAV with IBD were identified retrospectively. Data were abstracted from direct medical chart review. Each IBD-IgAV case was matched to two controls with IgAV but without IBD. Results: Nine patients were identified (seven Crohn's disease, two ulcerative colitis). Mean length of time between IBD diagnosis and IgAV onset was 17.3 ± 19.9 years. For patients on biologic treatment for IBD, mean length of time between biologic initiation and IgAV onset was 3.3 ± 3.8 years. Active IBD at IgAV onset was present in 56%. Tumour necrosis factor inhibitors (TNFi) were used for IBD in 89%. At IgAV onset, six patients were on treatment with TNFi; one subsequently discontinued, two switched to another TNFi, and three continued. At the last follow-up, three of five patients who remained on TNFi had full resolution of IgAV despite ongoing TNFi use. No differences were seen between cases with IBD IgAV and matched non-IBD-IgAV controls regarding development of end-stage renal disease, resolution of haematuria or proteinuria, and time to complete IgAV response. Conclusion: Baseline characteristics and outcomes of patients with IBD-IgAV are similar to those with IgAV without IBD. Development of IgAV is not limited to patients with clinically active IBD. Whether TNFi use is related to the pathogenesis of IgAV in some patients with IBD remains unclear. Further research into pathophysiological connections between IBD and IgAV is needed.

Prebiotics and phytogenics functional additives in low fish meal and fish oil based diets for European sea bass (Dicentrarchus labrax): Effects on stress and immune responses.

The use of terrestrial raw materials to replace fish meal (FM) and fish oil (FO) in marine fish diets may affect fish growth performance and health. In the last years functional additives have been profiled as good candidates to reduce the effects on health and disease resistance derived from this replacement, via reinforcement of the fish immune system. In the present study, three isoenergetic and isonitrogenous diets with low FM and FO (10% and 6% respectively) were tested based on supplementation either with 0.5% galactomannanoligosaccharides (GMOS diet) or 0.02% of a mixture of essential oils (PHYTO diet), a non-supplemented diet was defined as a control diet. Fish were fed the experimental diets in triplicate for 9 weeks and then they were subjected to a stress by confinement as a single challenge (C treatment) or combined with an experimental intestinal infection with Vibrio anguillarum (CI treatment). Along the challenge test, selected stress and immunological parameters were evaluated at 2, 24 and 168h after C or CI challenges. As stress indicators, circulating plasma cortisol and glucose concentrations were analyzed as well as the relative gene expression of cyp11b hydroxylase, hypoxia inducible factor, steroidogenic acute regulatory protein, heat shock protein 70 and heat shock protein 90 (cyp11b, hif-1α, StAR, hsp70 and hsp90). As immune markers, serum and skin mucus lysozyme, bactericidal and peroxidase activities were measured, as well as gene expression of Caspase-3 (casp-3) and interleukin 1ß (il-1ß). The use of functional additives induced a significant (p < 0.05) reduction of circulating plasma cortisol concentration when confinement was the unique challenge test applied. Supplementation of PHYTO induced a down-regulation of cyp11b, hif-1α, casp-3 and il-1ß gene expression 2h after stress test, whereas StAR expression was significantly (p < 0.05) up-regulated. However, when combination of confinement stress and infection was applied (CI treatment), the use of PHYTO significantly (p < 0.05) down-regulated StAR and casp-3 gene expression 2h after challenge test, denoting that PHYTO diet reinforced fish capacity of stress response via protection of head kidney leucocytes from stress-related apoptotic processes, with lower caspase-3 gene expression and a higher il-1ß gene expression when an infection occurs. Additionally, dietary supplementation with GMOS and PHYTO compounds increased fish serum lysozyme after infection. Both functional additives entailed a better capability of the animals to cope with infection in European sea bass when fed low FM and FO diets.

Feeding European sea bass (Dicentrarchus labrax) juveniles with a functional synbiotic additive (mannan oligosaccharides and Pediococcus acidilactici): An effective tool to reduce low fishmeal and fish oil gut health effects?

The aim of this study was to assess the effects of dietary mannan oligosaccharides (MOS), Pediococcus acidilactici or their conjunction as a synbiotic in low fish meal (FM) and fish oil (FO) based diets on European sea bass (Dicentrarchus labrax) disease resistance and gut health. For that purpose, sea bass juveniles were fed one of 6 diets containing different combinations of MOS (Biomos® and Actigen©; Alltech, Inc., Kentucky, USA) and Pediococcus acidilactici (BAC, Bactocell®; Lallemand Inc., Cardiff, UK) replacing standard carbohydrates as follows (MOS (%)/BAC (commercial recommendation): high prebiotic level (HP) = 0.6/0, low prebiotic level (LP) = 0.3/0, only probiotic (B) = 0/+, high prebiotic level plus probiotic (HPB) = 0.6/+, low prebiotic level plus probiotic (LPB) = 0.3/+, control (C) = 0/0 for 90 days. After 60 and 90 days of feeding trial, fish were subjected to an experimental infection against Vibrio anguillarum. Additionally, inducible nitric oxide synthase (iNOS) and tumor necrosis factor α (TNFα) gut patterns of immunopositivity and major histocompatibility complex class II (MHCII), transforming growth factor ß (TGF-ß), regulatory T-cell subset (CD4+T lymphocytes) and effector T cell (CD8α+T lymphocytes) gene expression patterns in gut by in situ hybridization were evaluated after 90 days of feeding. The effects of both additives on posterior gut through Gut Associated Lymphoid Tissue (GALT) gene expression was also studied. Fish fed the prebiotic and its combination with P. acidilactici presented increased weight regardless of the dose supplemented after 90 days of feeding, however no effect was detected on somatic indexes. For posterior gut, morphometric patterns and goblet cells density was not affected by MOS, P. acidilactici or its combination. Anti-iNOS and anti-TNFα gut immunopositivity patterns were mainly influenced by MOS supplementation and not by its combination with P. acidilactici. MHCII-ß, TCR-ß, CD4 and CD8-α positive cells distribution and incidence was not affected by diet. Fish fed HP dose presented a clear up-regulation of TNF-α, cyclooxygenase-2 (COX-2), CD4 and IL10, whereas P. acidilactici dietary supplementation increased the number of interleukin-1ß (IL1ß) and COX-2 gene transcripts. Synbiotic supplementation resulted in a reduction of MOS-induced gut humoral proinflammatory response by increasing the expression of some cellular-immune system related genes. Fish mortality after V. anguillarum infection was reduced in fish fed LPB and LP diets compared to fish fed the non-suppelmented diet after 90 days of feeding. Thus, overall pointing to the combination of a low dose of MOS and P. acidilactici as synbiont (LPB) as a viable tool to potentiate European sea bass juvenile's growth and disease resistance when supplemented in low FM and FO diets.

Autoimmune myelofibrosis with pancytopenia as a presenting manifestation of systemic lupus erythematosus responsive to mycophenolate mofetil.

Hematological abnormalities, such as anemia, leucopenia, and thrombocytopenia, secondary to peripheral destruction, are common in systemic lupus erythematosus (SLE). However, cytopenias from autoimmune myelofibrosis (AIMF) are extremely uncommon in SLE, with less than 40 reported cases in the literature. We report the case of a 33-year-old female who presented with bullous skin lesions and pancytopenia as the presenting manifestation of what was ultimately diagnosed as SLE with AIMF. She responded well to glucocorticoids and mycophenolate mofetil.