Dear Editor, Allergic bronchopulmonary aspergillosis (ABPA) is a pulmonary disorder caused by exaggerated hypersensitivity to Aspergillus species, namely Aspergillus fumigatus. It is characterized by ...poorly controlled asthma, recurrent pulmonary infiltrates, and bronchiectasis often with thick, viscous eosinophilic mucus plugging. Although the mechanism of this hyperdense mucus generation is poorly understood, the severity of this mucus plugging, which may represent severe inflammation, is associated with recurrent relapse. Extracellular trap cell death (ETosis) of human leucocytes, particularly neutrophils and eosinophils, is a distinct programmed cell death pathway. It is characterized by release of filamentous chromatin structures (DNA traps) in contrast to cell apoptosis. DNA trap formation is considered to be an innate immune reaction by ensnaring microorganisms, although its excess production could be pathogenic. For instance, in thick and viscous airway fluids from patients with cystic fibrosis, large numbers neutrophil-derived DNA traps are present (also called neutrophil extracellular traps; NETs).
Idiopathic pure red cell aplasia (PRCA) and secondary PRCA associated with thymoma and large granular lymphocyte leukemia are generally considered to be immune-mediated. The PRCA2004/2006 study ...showed that poor responses to immunosuppression and anemia relapse were associated with death. PRCA may represent the prodrome to MDS. Thus, clonal hematopoiesis may be responsible for treatment failure. We investigated gene mutations in myeloid neoplasm-associated genes in acquired PRCA. We identified 21 mutations affecting amino acid sequences in 11 of the 38 adult PRCA patients (28.9%) using stringent filtering of the error-prone sequences and SNPs. Four PRCA patients showed 7 driver mutations in TET2, DNMT3A and KDM6A, and 2 PRCA patients carried multiple mutations in TET2. Five PRCA patients had mutations with high VAFs exceeding 0.3. These results suggest that clonal hematopoiesis by stem/progenitor cells might be related to the pathophysiology of chronic PRCA in certain adult patients.
Urine xanthine crystals are remarkably rare but can be observed by routine urine microscopy. We report the results of a 67-year-old man with T-cell-prolymphocytic leukemia whose urine contained ...xanthine crystals after chemotherapy and prophylactic administration of febuxostat. Accumulation of xanthine was due to tumor lysis syndrome causing a massive release of DNA. The metabolized DNA caused an increase of xanthine, which was not readily converted to uric acid by xanthine oxidase because of febuxostat inhibition of this enzyme.
Background
Several recent studies in patients with idiopathic membranous nephropathy (iMN) from Western and Asian counties showed that some single nucleotide polymorphisms (SNPs) within the
PLA2R1
...and
HLA
-
DQA1
genes are significantly associated with iMN. However, there is only 1 report on analysis of
PLA2R1
and
HLA
regions in Japanese patients with iMN.
Methods
A total of 58 patients with iMN, 26 patients with secondary MN (sMN), and 50 patients with other diseases were enrolled. All patients were Japanese. We selected 6 SNPs within
PLA2R1
and 1 SNP within
HLA
-
DQA1
, which were significantly associated with iMN in reported white European cohorts, and sequenced these exons using genomic DNA prepared from peripheral mononuclear cells from each patient. We then analyzed differences in
PLA2R1
and
HLA
-
DQA1
sequence variants among the 3 groups.
Results
Genotypic and allelic frequency distributions for 3 out of 6 SNPs within
PLA2R1
, rs3749117, rs35771982, and rs2715918 were significantly different between the iMN and control groups. Allelic frequency distributions for SNP rs2187668 within
HLA
-
DQA1
were significantly different between the iMN and control groups. There were no correlations between
PLA2R1
and
HLA
-
DQA1
sequence variants and clinical parameters in patients with iMN. There were no significant differences in genotypic or allelic frequency distributions for examined SNPs between the sMN and control groups.
Conclusions
There are some differences in
PLA2R1
SNP distributions between previously reported cohorts from other countries and our Japanese cohort of patients with iMN, while there is a significant association between SNP rs35771982 and iMN in most of reported cohorts.
Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is a systemic inflammatory disorder categorized as small-vessel vasculitis. We herein report an elderly Japanese man with AAV ...(granulomatosis with polyangiitis affecting the eyes, nose, lungs, and kidneys) who also showed periaortitis at the diagnosis and developed cranial hypertrophic pachymeningitis (HP) during steroid maintenance therapy. His consciousness disturbance caused by HP improved after steroid pulse therapy, but he died of aspiration pneumonia. Autopsy findings showed giant cells in the thickened pachymeninges and obsolete inflammatory lesions in the aortic adventitia and renal tubulointerstitium. This is the first case of AAV complicated by periaortitis and cranial HP.
Recent evidence has shown that eosinophils play an important role in metabolic homeostasis through Th2 cytokine production. GPR120 (FFA4) is a G protein-coupled receptor (GPCR) for long-chain fatty ...acids that functions as a regulator of physiological energy metabolism. In the present study, we aimed to investigate whether human eosinophils express GPR120 and, if present, whether it possesses a functional capacity on eosinophils. Eosinophils isolated from peripheral venous blood expressed GPR120 at both the mRNA and protein levels. Stimulation with a synthetic GPR120 agonist, GW9508, induced rapid down-regulation of cell surface expression of GPR120, suggesting ligand-dependent receptor internalization. Although GPR120 activation did not induce eosinophil chemotactic response and degranulation, we found that GW9508 inhibited eosinophil spontaneous apoptosis and Fas receptor expression. The anti-apoptotic effect was attenuated by phosphoinositide 3-kinase (PI3K) inhibitors and was associated with inhibition of caspase-3 activity. Eosinophil response investigated using ELISpot assay indicated that stimulation with a GPR120 agonist induced IL-4 secretion. These findings demonstrate the novel functional properties of fatty acid sensor GPR120 on human eosinophils and indicate the previously unrecognized link between nutrient metabolism and the immune system.
Recent studies on systemic lupus erythematosus (SLE) revealed that microRNAs (miRNAs or miRs) were involved in its pathogenesis. However, only a limited number of miRNAs have been examined.
We ...performed quantitative real-time reverse transcription-polymerase chain reaction analyses of peripheral blood mononuclear cells (PBMCs) obtained from 31 untreated SLE patients and 31 healthy subjects to examine the expression levels of miR-155, miR-17, and miR-181b, as well as those of activation-induced cytidine deaminase (AID) and interferon-α (IFN-α) messenger RNAs (mRNAs). We examined the relationship between miR-181b, AID, and IFN-α with a luciferase reporter assay.
The expression levels of miR-155, miR-17, and miR-181b were significantly lower in SLE patients than those in healthy controls, whereas those of AID and IFN-α mRNAs were significantly higher in SLE patients than those in healthy controls. The expression levels of miR-155, miR-17, and miR-181b inversely correlated with those of AID and IFN-α mRNAs in SLE patients. The results of the luciferase reporter assay revealed that miR-181b negatively regulated AID and IFN-α.
The results of the present study demonstrated for the first time that there is a differential expression and inverse correlation between the levels the miR-155, miR-17, and miR-181b and target molecules, AID and IFN-α mRNAs, in PBMCs of untreated SLE patients. These alterations may contribute to the pathogenesis of SLE.
To validate the 2010 histopathological classification system of anti-neutrophil cytoplasmic antibodies (ANCA)-associated glomerulonephritis (GN) in a Japanese single-center cohort.
We retrospectively ...studied 54 patients (28 renally limited pauci-immune GN, 25 microscopic polyangiitis, and one Churg-Strauss syndrome).
There were 17 patients with focal GN, eight patients with crescentic GN, 19 patients with mixed GN, and 10 patients with sclerotic GN. Detailed information regarding treatment was available in 39 patients. All these patients were treated with steroids with or without immunosuppressive agents. Hemodialysis was introduced in two patients with crescentic GN and three patients with sclerotic GN. During the follow-up period, 27 of 54 patients died. The major cause of death was pneumonia. Significant differences were observed in estimated glomerular filtration rate among patients with focal, crescentic, mixed, and sclerotic GN at entry and 1- and 5-year follow-up. Patients with focal GN had preserved renal function and favorable outcome.
Our validation study suggests that the 2010 histopathological classification of ANCA-associated GN might aid in prognostication of patients at the time of diagnosis and in therapy selection.
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