Cryptococcosis with pulmonary cavitation in an immunocompetent child: a case report and literature review.

BACKGROUND: Pulmonary cryptococcosis (PC) rarely occurs in immunocompetent children. CASE PRESENTATION: A 13-year-old boy was admitted to the First Affiliated Hospital of Ningbo University in February 2023 with complaints of cough and chest pain. Physical examination showed slightly moist rales in the right lung. Chest computed tomography (CT) suggested a lung lesion and cavitation. Blood routine test, lymphocyte subsets, immunoglobulin, and complement tests indicated that the immune system was normal. However, the serum cryptococcal antigen test was positive. Next-generation sequencing revealed Cryptococcus infection. The child was diagnosed with PC and was discharged after treating with fluconazole 400 mg. Four months later, chest CT showed that the lung lesion diminished, and reexamination of serum cryptococcal antigen test turned positive. CONCLUSION: PC should be considered in an immunocompetent child with pulmonary cavities with nonspecific symptoms.

HLA-DRB5 Overexpression Promotes Platelet Reduction in Immune Thrombocytopenia Mice Model by Facilitating MHC-II-Mediated Antigen Presentation.

INTRODUCTION: Major histocompatibility complex II (MHC-II)-mediated antigen presentation contributes to the pathogenesis of immune thrombocytopenia (ITP). Human leukocyte antigen (HLA)-DRB5 is an MHC-II molecule and this study aims to investigate its role and mechanisms in ITP development. METHODS: Guinea pig anti-mouse platelet (PLT) serum-induced ITP mice received tail vein injection of HLA-DRB5 overexpressing adenoviral vector/immune receptor expressed on myeloid cells-1 (IREM-1) monoclonal antibody (mAb). PLT count changes in mice blood were assessed by a hematology analyzer. MHC-II/CD80/CD86 expression in mice blood was measured by quantitative real-time-PCR and immunofluorescence assay. CD8+ T-cell proportion in mice blood was detected by flow cytometry. RESULTS: HLA-DRB5 overexpression exacerbated PLT reduction since the 5th day of the establishment of ITP mice model and enhanced MHC-II/CD80/CD86 expression upregulation as well as CD8+ T-cell ratio elevation in the blood of ITP mice, while its effects were reversed by IREM-1 mAb. CONCLUSION: HLA-DRB5 overexpression upregulates MHC-II-mediated antigen presentation to CD8+ T cells, thus lowering PLT count in the ITP mice model.

Tumor-suppressing effects of miR-381-3p in pediatric acute myeloid leukemia via ROCK1 downregulation.

MicroRNA (miR)-381-3p is the newly discovered tumor-associated miRNA, which is frequently associated with diverse human malignancies; but, it is still unknown about its effect on acute myeloid leukemia (AML) in children. This work focused on exploring miR-381-3p's effect on childhood AML and identifying the possible mechanisms facilitating new treatment development. Using qRT-PCR analysis, miR-381-3p expression remarkably reduced in pediatric AML patients and AML cell lines (HL-60 and U937). Following transfection of miR-381-3p mimic or inhibitor into HL-60 and U937 cells, we conducted MTT assay to evaluate cell proliferation, flow cytometry (FCM) to measured cell apoptosis and cell cycle, whereas Transwell assays to detect cell invasion and migration. Our results demonstrated that miR-381-3p overexpression remarkably repressed cell growth, invasion and migration; additionally, miR-381-3p overexpression resulted in arrest of cell cycle and enhanced cell apoptosis. In contrast, miR-381-3p knockdown led to an opposite effect. Moreover, we predicted miR-381's target gene and validated it by luciferase reporter assay and TargetScan, separately. We identified miR-381-3p's binding site in ROCK1 3'-UTR. As revealed by Western-blot (WB) assay, miR-381-3p overexpression notably suppressed ROCK1 level. Moreover, restoring ROCK1 expression abolished miR-381-3p's inhibition on cell proliferation, invasion and migration. Data in this work indicated the role of miR-381-3p as the tumor suppressor within pediatric AML by targeting ROCK1. Therefore, miR-381-3p might serve as a potential therapeutic target for the treatment of pediatric AML.

Elevated Interleukin 1ß and Interleukin 6 Levels in the Serum of Children With Hyperuricemia.

PURPOSES: The aim of this study was to investigate the serum levels and clinical significance of interleukin 1ß (IL-1ß) and IL-6 in children with hyperuricemia (HUA). METHODS: We included 71 children with HUA and 71 children with no HUA as control subjects. Children with HUA were divided into groups I and II according to whether they had a history of acute gout-like attacks (including sudden monoarthritis of rapid onset with intense pain and swelling). Group I was examined twice (A, in the acute phase; B, in the remission phase). Serum IL-1ß and IL-6 levels were measured by enzyme-linked immunosorbent assay. RESULTS: Serum IL-1ß and IL-6 levels were increased in children with HUA and were overall statistically different from the control group (P < 0.05, respectively). Serum IL-1ß and IL-6 were significantly higher in group IA in comparison with group IB, group II, and control subjects (P < 0.05, respectively), as well as in groups IB and II compared with control subjects (P < 0.05, respectively). In group IB, the serum IL-1ß and IL-6 concentrations were higher than those in group II, but there were no statistical differences (P > 0.05). In addition, in children with HUA, serum IL-1ß and IL-6 levels were positively associated with white blood cell count, neutrophil count, monocyte count, uric acid levels, erythrocyte sedimentation rate, C-reactive protein, blood urea nitrogen, and serum creatinine levels (all P < 0.05), but were not associated with triglycerides, total cholesterol, low-density lipoprotein cholesterol, or high-density lipoprotein cholesterol levels (all P > 0.05). CONCLUSION: IL-1ß and IL-6 levels are increased in children with hyperuricemia, even if they have not had acute gout. Further studies are necessary to fully characterize the significance of IL-1ß and IL-6 found in HUA children, and whether they could be correlated with long-term prognosis.

Urinary Macrophage Migration Inhibitory Factor as a Noninvasive Biomarker in Pediatric Henoch-Schönlein Purpura Nephritis.

PURPOSES: The aims of this study were to investigate urinary macrophage migration inhibitory factor (MIF) levels and their clinical significance in Henoch-Schönlein purpura (HSP) children with or without nephritis (N) and to assess the influence of steroid treatment on the urine MIF levels of HSPN patients. METHODS: Group I comprised 35 children with HSPN who were examined twice (A before treatment and B after steroid treatment). Group II comprised 41 children with HSP. The control group included 32 healthy children. Urinary MIF levels were measured via enzyme linked immunosorbent assay. The levels of serum creatinine, blood urea nitrogen, urinary microalbumin (mAlb), and 24-hour proteinuria were performed to determine their associations with MIF levels. RESULTS: Urinary MIF levels were significantly higher in group I compared with group II and the control group (P < 0.01); however, no significant difference was found between group II and the control group (P > 0.05). Upon examination, albeit urinary MIF concentration was significantly lower in group IB compared with group IA (P < 0.05), these concentrations were statistically higher than that of group II (P < 0.05). In addition, in the HSPN patients, the urinary MIF was positively associated with urinary microalbumin and 24-hour proteinuria but no association with serum creatinine and blood urea nitrogen. CONCLUSIONS: Elevated urinary MIF levels were found to be correlated with proteinuria in pediatric HSPN. An obvious decrease in urinary MIF concentrations among the children with HSPN was associated with steroid treatment. Urinary MIF can be used as a noninvasive biomarker in pediatric HSPN.

HLA-DRB5 promotes immune thrombocytopenia via activating CD8+ T cells.

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by a low platelet (PLT) count and a high risk of bleeding, the clinical treatment for which still needs to be upgraded. Based on the critical role of human leukocyte antigen class II heterodimer ß5 (HLA-DRB5) in immune system, we herein investigated its effect on ITP. ITP murine models were established by the injection of guinea pig anti-mouse platelet serum (GP-APS), and the PLT of mouse peripheral blood was counted during the modeling. Quantitative real-time reverse transcription polymerase chain reaction, western blot and immunofluorescence assay was performed to quantify expressions of HLA-DRB5, major histocompatibility complex II (MHC-II) and co-stimulatory molecules (CD80, CD86). Flow cytometry was conducted to analyze the percentage of CD8+ T cells. As a result, the PLT count was decreased in mouse peripheral blood. Expressions of HLA-DRB5, MHC-II and co-stimulatory molecules, as well as the percentage of CD8+ T cells were elevated in peripheral blood of ITP mice. HLA-DRB5 knockdown mitigated ITP by increasing peripheral PLT level, downregulating expressions of MHC-II and co-stimulatory molecules and inactivating CD8+ T cells. Collectively, the downregulation of HLA-DRB5 restores the peripheral PLT count in ITP mice by reducing MHC-II-mediated antigen presentation of macrophages to inhibit the activation of CD8+ T cells.

Urate crystal deposition in hyperuricemic children: a dual energy computed tomography study.

INTRODUCTION: The incidence of hyperuricemia (HUA) at younger ages is increasing along the coastal regions of China. This study aimed to compare the frequency of dual energy CT (DECT) urate crystal deposition between symptomatic hyperuricemic children and asymptomatic hyperuricemic children. MATERIAL AND METHODS: Fifty-six hyperuricemic children were divided into a Joint Group (n = 33) and an Asymptomatic Group (n = 23) according to whether they had a history of arthritis symptoms, which includes rapid onset monoarthritis with intense pain and swelling. We analyzed DECT scans of their feet from the Joint Group and the Asymptomatic Group and compared their clinical features. RESULTS: DECT urate deposits were observed in 28/33 (84.8%) children with symptomatic HUA and 14/23 (60.9%) with asymptomatic HUA. We found 60 areas of urate deposition in the Joint Group; DECT urate crystal deposition was most frequently observed in the first metatarsophalangeal (MTP) joint (30.0%), ankle joint (15.0%), and calcaneus (13.3%). 39 urate deposits were found in the Asymptomatic Group; DECT urate crystal deposition was most frequently observed in the calcaneus (25.6%), the first MTP joint (17.9%), and the first phalanx (15.4%). CONCLUSIONS: Urate deposition can occur in children with HUA, and these deposits occur more frequently in hyperuricemic children with a history of arthritis symptoms. Also, the urate deposition in the first MTP joint and calcaneus was more prevalent than in other joints. It is important to give more attention to hyperuricemic children.

Elevated urinary monocyte chemoattractant protein-1 levels in children with Henoch-Schonlein purpura nephritis.

BACKGROUND: Chemokine monocyte chemoattractant protein-1 (MCP-1) has been proved as a potential urinary biomarker in nephropathies. The aim of this study was to investigate the urinary monocyte chemoattractant protein-1 (MCP-1) levels and clinical significance in Henoch-Schonlein purpura (HSP) children with and without nephritis and determine the association of MCP-1 with proteinuria. METHODS: A total of 261 HSP children-with or without nephritis-and 84 healthy control children were enrolled in this study. Of these, 126 HSP nephritis (HSPN) children were subdivided into three groups according to total urine protein in 24 h (TUP): Group A, mild proteinuria group with TUP <25 mg/kg; Group B, moderate proteinuria group with TUP ≥25 mg/kg and <50 mg/kg; Group C, severe proteinuria group with TUP ≥50 mg/kg. Urinary MCP-1 levels were determined by ELISA. Levels of serum creatinine (Cr), blood urea nitrogen (BUN), urinary α1-micro globulin (α1-MG), micro-albumin (mAlb), immunoglobulin G (IgG), transferrin (TRF) and TUP were performed to determine their associations with MCP-1. RESULTS: Urinary MCP-1 was significantly higher in HSPN group in comparison with HSP group and controls (P < 0.05), but no significant difference was found between the HSP group and the healthy group (P > 0.05). The levels of urinary MCP-1 increased in parallel to the enhancement of total urine protein in 24 h in HSPN patients. There were statistically significant differences among these three groups of HSPN children (p < 0.05). Urinary MCP-1 correlated positively with urinary α1-MG, mAlb, IgG, TRF and TUP in HSPN, whereas no correlation was observed with serum Cr and BUN. CONCLUSIONS: MCP-1 was elevated in children with HSPN and correlated with proteinuria. Urinary MCP-1 could be used as a suitable, non-invasive biomarker to provide valuable information not only for the diagnosis of HSPN, but also for evaluation of severity of renal damage.