Monitoring serum IL-18 levels is useful for treatment of a patient with systemic juvenile idiopathic arthritis complicated by macrophage activation syndrome

Systemic juvenile idiopathic arthritis (sJIA) is a systemic inflammatory disease characterized by arthritis, spiking fever and a skin rash that is frequently complicated by macrophage activation syndrome (MAS), a life-threatening disorder. We report a 22-month-old girl with sJIA who developed severe MAS but was successfully treated with corticosteroids, cyclosporin A, and non-steroidal anti-inflammatory drugs by monitoring serum IL-18 levels. IL-18 is an extremely useful cytokine for monitoring the activity of sJIA and MAS, and serum IL-18 can be used as an indicator for the effectiveness of treatment and the decision to discontinue therapy.ArticlePEDIATRIC RHEUMATOLOGY. 9:15 (2011)journal articl

Clonal expansion of Epstein-Barr virus (EBV)-infected γδ T cells in patients with chronic active EBV disease and hydroa vacciniforme-like eruptions

Chronic active Epstein-Barr virus (EBV) disease (CAEBV) is a systemic EBV-positive lymphoproliferative disorder characterized by fever, lymphadenopathy, and splenomegaly. Patients with CAEBV may present with cutaneous symptoms, including hypersensitivity to mosquito bites and hydroa vacciniforme (HV)-like eruptions. HV is a rare photodermatosis characterized by vesicles and crust formation after exposure to sunlight, with onset in childhood, and is associated with latent EBV infection. While γδ T cells have recently been demonstrated to be the major EBV-infected cell population in HV, the immunophenotypic features of EBV-infected γδ T cells in CAEBV with HV-like eruptions or HV remain largely undetermined. We describe three patients with CAEBV whose γδ T cells were found to be the major cellular target of EBV. HV-like eruptions were observed in two of these patients. A clonally expanded subpopulation of γδ T cells that were highly activated and T cell receptor Vγ9- and Vδ2-positive cells was demonstrated in all patients. We also show that the clonally expanded γδ T cells infiltrated into the HV-like eruptions in one patient from whom skin biopsy specimens were available. These results suggest the pathogenic roles of clonally expanded γδ T cells infected by EBV in patients with CAEBV and HV-like eruptions. © 2012 The Japanese Society of Hematology

A Syrian Refugee in Iraq Diagnosed as a Case of IL12RB1 Deficiency in Japan Using Dried Blood Spots

Mendelian susceptibility to mycobacterial diseases (MSMD) is a rare condition of primary immunodeficiency disorder. Interleukin-12 receptor β1 (IL12RB1) deficiency, is the most common genetic etiology of MSMD, which is characterized by the selective predisposition to clinical disease caused by weakly-virulent mycobacteria, such as Bacillus Calmette-Guérin (BCG) vaccines, and environmental non-tuberculous mycobacteria (NTM). To the best of our knowledge, this is the first case of IL12RB1 deficiency to be reported from Iraq. Our case is an 8-year-old Syrian girl, for first-cousin parents, with a refugee-status in the North of Iraq. She had a history of disseminated BCG infection 2 months after receiving BCG vaccine, in addition to repeated episodes of mild or severe illnesses, such as maculopapular skin rash, lymphadenopathy, gastroenteritis, meningitis, and clinically diagnosed tuberculosis (TB) based on local TB-prevalence setting. Because of limited medical facilities in the war-torn countries; in Syria and Iraq, no diagnosis could be reached. We used Flinders Technology Associates (FTA) cards to transfer her bone marrow aspirate to Japan. A homozygous IL12RB1 mutation was detected by whole exome sequencing in Japan, using genomic-DNA extracted from dried bone marrow sample spots on FTA filter paper. In conclusion, diagnosis of MSMD due to IL12RB1 deficiency was possible by transferring the FTA sample of the patient for genetic evaluation in Japan. Our report recalls the need of pediatricians in countries with TB-prevalence and high parental consanguinity, to consider IL12RB1 deficiency in the differential diagnosis of a child with clinical evidence of TB, especially with the history of disseminated BCG disease

Rapid Detection of Intracellular p47phox and p67phox by Flow Cytometry; Useful Screening Tests for Chronic Granulomatous Disease

Chronic granulomatous disease (CGD) is caused by defects of NADPH oxidase. The diagnosis of CGD can be made by analysis of NADPH oxidase activity, however, identification of the CGD subgroups is required before performing mutation analysis. The membrane-bound subunits, gp91phox and p22phox, can be quickly analyzed by flow cytometry, unlike the cytosolic components, p47phox and p67phox. We evaluated the feasibility of flow cytometric detection of p47phox and p67phox with specific monoclonal antibodies in two patients with p47phox deficiency and 7 patients with p67phox deficiency. Consistent with previous observations, p47phox and p67phox were expressed in phagocytes and B cells, but not in T or natural killer cells, from normal controls. In contrast, patients with p47phox and p67phox deficiency showed markedly reduced levels of p47phox and p67phox, respectively. These techniques will be useful to rapidly assess the expression of the cytosolic components, p47phox and p67phox, and represents important secondary screening tests for CGD. © 2013 Springer Science+Business Media New York

Superoxide-Generating Nox5? Is Functionally Required for the Human T-Cell Leukemia Virus Type 1-Induced Cell Transformation Phenotype.

Human T-cell leukemia virus type 1 (HTLV-1) is associated with adult T-cell leukemia (ATL) and transforms T cells in vitro. To our knowledge, the functional role of reactive oxygen species (ROS)-generating NADPH oxidase 5 (Nox5) in HTLV-1 transformation remains undefined. Here, we found that Nox5? expression was upregulated in 88% of 17 ATL patient samples but not in normal peripheral blood T cells. Upregulation of the Nox5? variant was transcriptionally sustained by the constitutive Janus family tyrosine kinase (Jak)-STAT5 signaling pathway in interleukin-2 (IL-2)-independent HTLV-1-transformed cell lines, including MT1 and MT2, whereas it was transiently induced by the IL-2-triggered Jak-STAT5 axis in uninfected T cells. A Nox inhibitor, diphenylene iodonium, and antioxidants such as N-acetyl cysteine blocked proliferation of MT1 and MT2 cells. Ablation of Nox5? by small interfering RNAs abrogated ROS production, inhibited cellular activities, including proliferation, migration, and survival, and suppressed tumorigenicity in immunodeficient NOG mice. The findings suggest that Nox5? is a key molecule for redox-signal-mediated maintenance of the HTLV-1 transformation phenotype and could be a potential molecular target for therapeutic intervention in cancer development.HTLV-1 is the first human oncogenic retrovirus shown to be associated with ATL. Despite the extensive study over the years, the mechanism underlying HTLV-1-induced cell transformation is not fully understood. In this study, we addressed the expression and function of ROS-generating Nox family genes in HTLV-1-transformed cells. Our report provides the first evidence that the upregulated expression of Nox5? is associated with the pathological state of ATL peripheral blood mononuclear cells and that Nox5? is an integral component of the Jak-STAT5 signaling pathway in HTLV-1-transformed T cells. Nox5?-derived ROS are critically involved in the regulation of cellular activities, including proliferation, migration, survival, and tumorigenicity, in HTLV-1-transformed cells. These results indicate that Nox5?-derived ROS are functionally required for maintenance of the HTLV-1 transformation phenotype. The finding provides new insight into the redox-dependent mechanism of HTLV-1 transformation and raises an intriguing possibility that Nox5? serves as a potential molecular target to treat HTLV-1-related leukemia

Bacteremia due to Moraxella osloensis: a case report and literature review

Herein we report the case of a 10-year-old boy with an autosomal mosaic mutation who developed bacteremia. The causative agent was identified as Moraxella osloensis by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and 16S rRNA gene sequencing. In the pediatric population, there have been 13 case reports of infection attributed to M. osloensis and this is the fifth reported case of pediatric bacteremia due to M. osloensis. After Moraxella species infection was confirmed, the patient recovered with appropriate antimicrobial therapy. It is important to consider that M. osloensis can cause serious infections, such as bacteremia, in otherwise healthy children. Keywords: Moraxella osloensis, Bacteremia, MALDI-TOF MS, 16S rRNA gene sequencin

Evaluation of Mucorales DNA load in cerebrospinal fluid in a patient with possible cerebral mucormycosis treated with intravenous liposomal amphotericin B

We report the case of a 19-year-old male with possible cerebral mucormycosis following chemotherapy. We detected a Lichtheimia DNA load of 2.0 × 104 copies/ml in cerebrospinal fluid (CSF), although a CSF culture showed no growth. After treatment with intravenous liposomal amphotericin B, the Lichtheimia DNA load fell below the detection limit, and at the same time the patient's headache and imaging findings improved. The quantification of Mucorales DNA in CSF may be useful for evaluating cerebral mucormycosis