Our results demonstrated that IL-9 exerted pro-atherosclerotic effects in ApoE-/- mice at least partially by inducing VCAM-1 expression, which mediated inflammatory cell infiltration into atherosclerotic lesions.
Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is characterized by a wide range of dermatological and musculoskeletal manifestations, and its outcome has recently been improved greatly by optimizing management. However, the treatment strategies are not standardized and require further refinement. Secukinumab, a fully human monoclonal antibody targeting IL-17A, is approved for the treatment of autoimmune psoriasis, psoriatic arthritis (PsA), and ankylosing spondylitis (AS). Here, a 53-year-old man was diagnosed with AS, and he presented scattered pustulosis in both hands and feet with a 5-year history of recurrent lumbosacral area pain and abnormal pain in the neck and front chest area. Secukinumab improved the patient’s cutaneous lesion and prevented musculoskeletal pain by substituting adalimumab. Although only a few cases have been reported that secukinumab can effectively treat SAPHO syndrome complicated with AS, the efficacy remains controversial. Therefore, we hope to provide a novel valuable therapeutic strategy for SAPHO syndrome management, particularly in patients with skin lesions.
BACKGROUND:
Aberrant amino acid metabolism is implicated in cardiac hypertrophy, while the involvement of tryptophan metabolism in pathological cardiac hypertrophy remains elusive. Herein, we aimed to investigate the effect and potential mechanism of IDO1 (indoleamine 2,3-dioxygenase) and its metabolite kynurenine (Kyn) on pathological cardiac hypertrophy.
METHODS:
Transverse aortic constriction was performed to induce cardiac hypertrophy in IDO1-knockout (KO) mice and AAV9-cTNT-shIDO1 mice. Liquid chromatography–mass spectrometry was used to detect the metabolites of tryptophan-Kyn pathway. Chromatin immunoprecipitation assay and dual luciferase assay were used to validate the binding of protein and DNA.
RESULTS:
IDO1 expression was upregulated in both human and murine hypertrophic myocardium, alongside with increased IDO1 activity and Kyn content in transverse aortic constriction-induced mice’s hearts using liquid chromatography–mass spectrometry analysis. Myocardial remodeling and heart function were significantly improved in transverse aortic constriction-induced IDO1-KO mice, but were greatly exacerbated with subcutaneous Kyn administration. IDO1 inhibition or Kyn addition confirmed the alleviation or aggravation of hypertrophy in cardiomyocyte treated with isoprenaline, respectively. Mechanistically, IDO1 and metabolite Kyn contributed to pathological hypertrophy via the AhR (aryl hydrocarbon receptor)-GATA4 (GATA binding protein 4) axis.
CONCLUSIONS:
This study demonstrated that IDO1 deficiency and consequent Kyn insufficiency can protect against pathological cardiac hypertrophy by decreasing GATA4 expression in an AhR-dependent manner.
Hemophagocytic lymphohistiocytosis (HLH) is a severe and life-threatening hyperinflammatory condition characterized by excessive activation of macrophages and T cells and resulted in multi-organ dysfunction. HLH can be a primary disease or secondary to infections, malignancy, and some autoimmune diseases, including adult-onset Still’s disease (AOSD) and systemic lupus erythematosus (SLE). However, it is rare for HLH to occur as a secondary condition to drug-induced lupus erythematosus (DILE). In this report, we present a case of HLH as an unusual complication during SLE treatment in a 31-year-old male patient. The patient initially suffered from active chronic hepatitis B (CHB) and was treated with pegylated INFα-2b (Peg-INFα-2b), tenofovir disoproxil and lamivudine. After 19 months, CHB obtained biochemical and virological response with HBsAg positive to HBsAb. The patient developed fever, headache, and cytopenia after Peg-INFα-2b treatment for 33 months, and laboratory studies revealed that ANA and anti dsDNA were positive. He displayed 5 features meeting the HLH-2004 criteria for diagnosis including fever, pancytopenia, hyperferritinemia, high levels of soluble CD25, and hemophagocytosis on bone marrow biopsy. The patient was initiated with a combination treatment of intravenous methylprednisolone pulse therapy, oral cyclosporine, and etoposide (VP-16), which was followed by a course of oral prednisolone, intravenous cyclophosphamide pulse therapy, and entecavir with complete response. To our knowledge, this is the first report of IFN-α induced SLE complicating with HLH. Physicians should consider the potential autoimmune side effects of IFN-α therapy and be alert to insidious HLH in patients diagnosed with SLE.
Alport syndrome (AS) is a genetic disease with various manifestations, including hematuria, proteinuria, impaired renal function and potential ocular or auditory abnormalities. Mutations in the collagen type IV α 3 chain (COL4A3), collagen type IV α 4 chain and collagen type IV α 5 chain genes encoding the α3, α4 and α5 chains of type IV collagen may undermine glomerular basement membrane (GBM) integrity and cause persistent renal deterioration. In the present study, the case of a Chinese family diagnosed with AS was examined. Pedigree investigations and whole exome sequencing (WES) revealed the presence of two heterozygous mutations (c.2603G>A; p.G868E, and c.583G>A; p.G195S) in the COL4A3 gene. p.G868E was identified as the 'culprit' mutation, whereas p.G195S was identified as an 'auxiliary' mutation for AS with regards to the manifestations observed in the patients carrying each of the gene mutations. In conclusion, these findings suggested that c.2603G>A may be a novel overt pathogenic mutation site for autosomal dominant AS. In addition, WES may be effective for the early diagnosis and medical intervention of AS, and may be widely used for AS prognosis prediction and pre-implantation genetic diagnosis.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.