Patients with psoriasis are frequently complicated with metabolic syndrome; however, it is not fully understood how obesity and dyslipidemia contribute to the pathogenesis of psoriasis. To investigate the mechanisms by which obesity and dyslipidemia exacerbate psoriasis using murine models and neonatal human epidermal keratinocytes (NHEKs), we used wild-type and Apoe-deficient dyslipidemic mice, and administered a high-fat diet for 10 weeks to induce obesity. Imiquimod was applied to the ear for 5 days to induce psoriatic dermatitis. To examine the innate immune responses of NHEKs, we cultured and stimulated NHEKs using IL-17A, TNF-α, palmitic acid, and leptin. We found that obesity and dyslipidemia synergistically aggravated psoriatic dermatitis associated with increased gene expression of pro-inflammatory cytokines and chemokines. Treatment of NHEKs with palmitic acid and leptin amplified pro-inflammatory responses in combination with TNF-α and IL-17A. Additionally, pretreatment with palmitic acid and leptin enhanced IL-17A-mediated c-Jun N-terminal kinase phosphorylation. These results revealed that obesity and dyslipidemia synergistically exacerbate psoriatic skin inflammation, and that metabolic-disorder-associated inflammatory factors, palmitic acid, and leptin augment the activation of epidermal keratinocytes. Our results emphasize that management of concomitant metabolic disorders is essential for preventing disease exacerbation in patients with psoriasis.

Bacterial peritonitis is a serious complication of patients undergoing peritoneal dialysis (PD). Although the identification of causative organisms and use of appropriate antibiotics are essential for treatment, rare and fastidious bacteria are sometimes difficult to detect by conventional biochemical assays. Capnocytophaga canimorsus is a fastidious and slow-growing bacterium that forms a part of the normal oral flora of dogs and cats and is extremely rare as a peritonitis-causing organism. This report demonstrates the usefulness of a mass spectrometry-based technique in identifying such a rare organism in PD-related peritonitis and discusses the diagnosis and treatment of C. canimorsus peritonitis. A 49-year-old woman with type 2 diabetes mellitus underwent PD for two years. Repeated exit-site infections led to subcutaneous pathway diversion two months ago. She was hospitalized with fever and abdominal pain as well as cloudy dialysis effluent. Laboratory data revealed increased serum C-reactive protein level and white blood cell (WBC) count in the effluent. Her exit site had no sign of infection, leading to the diagnosis of PD-related peritonitis. Initial therapy with intraperitoneal ceftazidime immediately ameliorated her symptoms, and the WBC count in the effluent normalized in five days. Culture test results of the dialysis effluent on admission were negative with no information regarding the infection route. However, mass spectrometry (MALDI Biotyper, Bruker Daltonics) successfully obtained the specific spectral pattern for C. canimorsus. She had four cats in her house and was advised not to allow the cats in the room where the bag exchange took place. C. canimorsus is a rare cause of peritonitis in PD patients and is usually susceptible to intraperitoneal third-generation cephalosporins. This mass spectrometry-based bacterial identification method could provide more opportunities to identify uncommon causes and promote appropriate antibiotics therapy in PD-related peritonitis.

Background: The adaptor protein Src homology 3 domain-binding protein 2 (SH3BP2) is widely expressed in immune cells. It controls intracellular signaling pathways. The present study was undertaken to investigate the role of SH3BP2 in a murine systemic lupus erythematosus model. Methods: For the lupus model, we used Fas^lpr/lpr mice. Clinical and immunological phenotypes were compared between Fas^lpr/lpr and SH3BP2-deficient Fas^lpr/lpr mice. Splenomegaly and renal involvement were assessed. Lymphocyte subsets in the spleen were analyzed by flow cytometry. To examine the role of SH3BP2 in specific cells, B cell-specific SH3BP2-deficient lupus mice were analyzed; T cells and bone marrow-derived dendritic cells and macrophages were analyzed in vitro. Results: SH3BP2 deficiency significantly reduced lupus-like phenotypes, presented as splenomegaly, renal involvement, elevated serum anti-dsDNA antibody, and increased splenic B220⁺CD4⁻CD8⁻ T cells. Notably, SH3BP2 deficiency in B cells did not rescue the lupus-like phenotypes. Furthermore, SH3BP2 deficiency did not substantially affect the characteristics of T cells and macrophages in vitro. Interestingly, SH3BP2 deficiency suppressed the differentiation of dendritic cells in vitro and reduced the number of dendritic cells in the spleen of the lupus-prone mice. Conclusions: SH3BP2 deficiency ameliorated lupus-like manifestations. Modulating SH3BP2 expression could thus provide a novel therapeutic approach to autoimmune diseases.

Lymphoproliferative disorders (LPDs) are sometimes found in patients with autoimmune diseases receiving immunosuppressive treatments. However, LPDs in patients with Takayasu arteritis (TAK) were not reported previously. A 41-year-old woman with TAK and ulcerative colitis (UC) maintained remission with 5 mg/day of prednisolone (PSL) and 100 mg/day of azathioprine (AZA). However, the follow up colonoscopy showed reddish, submucosal lesion in the rectum, and histological examination revealed medium-to-large-sized atypical lymphocytes proliferating in the mucosal layer. These lymphoid cells were CD20 positive and Epstein–Barr encoding region (EBER) positive, demonstrating EB virus-associated LPD. After the diagnosis, AZA was discontinued and rituximab (RTX) was initiated for treatment of both LPD and TAK. A follow-up colonoscopy after three months showed no abnormal findings and the remission of both UC and TAK was maintained. As an increased risk of LPD has been reported in patients with inflammatory bowel disease receiving thiopurines, LPD in our case might be related with complication of UC and use of AZA. RTX might be one of the treatment options for cases with TAK complicating other iatrogenic immunodeficiency-associated LPD.

腎血管性高血圧はさまざまな疾患を原因とする。今回我々は，潰瘍性大腸炎に腎血管性高血圧を合併した症例を経験した。症例は40 歳男性。造影CT と血管造影で右腎動脈の閉塞と側副血行路の発達を認めた。さらに左腎区域動脈と肝動脈の狭小化，両側内腸骨動脈の閉塞と腹部大動脈の一部壁不整がみられた。FDG-PET で大動脈炎症候群は否定的であった。皮疹や結腸粘膜の生検で血管炎の所見は得られず，診断に苦慮した症例であった。