Identification of serological biomarkers for diagnosis of rheumatoid arthritis using a protein array-based approach / 南方医科大学学报

OBJECTIVE@#To study the cytokine patterns in patients with rheumatoid arthritis (RA) and healthy individuals and identify candidate serum biomarkers for clinical diagnosis of RA.@*METHODS@#This study was conducted among 59 patients diagnosed with RA in our hospital from 2015 to 2019 with 46 age- and gender-matched healthy subjects who received regular physical examinations in our hospital as the control group. Serological autoimmune profiles of 5 RA patients and 5 healthy control subjects were obtained from human cytokine microarrays. We selected 4 differentially expressed cytokines (LIMPII, ROBO3, Periostin and IGFBP-4) and 2 soluble cytokine receptors of interest (2B4 and Tie-2) and examined their serum levels using enzyme-linked immunosorbent assay in 54 RA patients and 41 healthy control subjects. Spearman correlation test was performed to assess the correlation of serum cytokine and soluble receptor expression levels with the clinical features including rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), disease activity score (DAS28) and health assessment questionnaire (HAQ). Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic capability of these cytokines.@*RESULTS@#We identified 6 dysregulated cytokines and soluble receptors (2B4, LIMPII, Tie-2, ROBO3, periostin and IGFBP-4) in RA patients (P < 0.01). The serum levels of LIMPII, ROBO3 and periostin were significantly correlated with the disease activity indicators including RF (P < 0.001), CRP (P < 0.001), DAS28 (P < 0.001) and HAQ (P < 0.001) in RA patients. Among the 6 candidate cytokines, 2B4 showed the largest area under the curve (AUC) of 0.861 for RA diagnosis (P < 0.001), followed then by LIMPII, ROBO3, periostin, Tie-2 and IGFBP-4.@*CONCLUSION@#Serum levels of LIMPII, ROBO3 and periostin can be indicative of the disease activity of RA, and serum 2B4, LIMPII, periostin, ROBO3, IGFBP-4 and Tie-2 levels may serve as biomarkers for the diagnosis of RA.

Progress of diagnosis and treatment of cytokine release syndrome after CD19 chimeric antigen receptor T cells therapy / 白血病·淋巴瘤

CD19 chimeric antigen receptor T cells (CAR-T) therapy is a new immunotherapy for B-cell hematological tumors, and has good efficacy. With the increase of its use, the incidence of immune effector cell-associated cytokine release syndrome is increasing, and further clinical research on its precise mechanism and treatment is urgently needed. This review summarizes the mechanisms, clinical manifestations, grading systems, treatments and management strategies of cytokine release syndrome.

Out-sourcing for Trans-presentation: Assessing T Cell Intrinsic and Extrinsic IL-15 Expression with Il15 Gene Reporter Mice

IL-15 is a cytokine of the common γ-chain family that is critical for natural killer (NK), invariant natural killer T (iNKT), and CD8 memory T cell development and homeostasis. The role of IL-15 in regulating effector T cell subsets, however, remains incompletely understood. IL-15 is mostly expressed by stromal cells, myeloid cells, and dendritic cells (DCs). Whether T cells themselves can express IL-15, and if so, whether such T cell-derived IL-15 could play an autocrine role in T cells are interesting questions that were previously addressed but answered with mixed results. Recently, three independent studies described the generation of IL-15 reporter mice which facilitated the identification of IL-15-producing cells and helped to clarify the role of IL-15 both in vitro and in vivo. Here, we review the findings of these studies and place them in context of recent reports that examined T cell-intrinsic IL-15 expression during CD4 effector T cell differentiation.

Establishment and preliminary application of real time PCR assay for quantitative detection of CRLF2 / 国际检验医学杂志

Objective To establish a real‐time quantitative PCR method for the detection of cytokine receptor‐like factor 2 (CRLF2) expression .Methods Specific primers amplification target gene CRLF2 and housekeeping genes ABL were designed ,the purified PCR products were performed the TA cloning .After bacterial colony PCR screening and sequencing ,then the recombinant plasmids DNA was extracted and measured by using UV spectrophotometer and converted to copies/mL concentration .Finally it was diluted for preparing the plasmid standard substance ,then the standard curve was drawn for observing the sensitivity and linear rang ,meanwhile the stability of the plasmid DNA was evaluated .This method was initially applied to detect the CRLF2 level of bone marrow mononuclear cells in 10 cases of healthy children and 10 cases of newly diagnosed acute lymphoblastic leukemia (ALL) .Results CRLF2 PCR product had a single specific melting curve;the linear detection range of the standard substance was 103 - 108 copies /ml;the plasmid standard substance by freeze‐thawing for 3 times remained stable;the CRLF2 level of clinical sample was within the linear detection range of standard substance .Conclusion The real‐time quantitative PCR method for CRLF2 established by our laboratory has good specificity ,linearity range and stability ,which can be applied to the quantitative detection of CRLF2 gene in clinical ALL children .

A review on the gene of CRLF2 in childhood B-cell precursor acute lymphocytic leukemia / 国际儿科学杂志

Current risk classification in childhood B-cell precursor acute lymphocytic leukemia has been used to modulate the intensity of treatment and prognosis assessment.However there are a significant proportion of relapses and deaths occur among childhood with good risk clinical characteristics and/or an excellent early response to therapy.So research about the aberrant expression of gene associated with relapse will improve cure rate.Aberrant expression of CRLF2 gene can be found in childhood B-cell precursor acute lymphocytic leukemia and associated with JAK aberrantion,BCR-ABL1-like signature,IKZF deletion.Over-expression of CRLF2 gene is associated with high risk relapse and poor outcome in childhood B-cell precursor acute lymphocytic leukemia,but its prognostic value is still controversial.This article mainly reviews the progress of CRLF2 gene in childhood B-cell precursor acute lymphocytic leukemia.

Effessian of cytokine receptor in depressive rats treated electroshock therapy / 重庆医科大学学报

Objective:To observe the expression of cytokine receptor in neuron and astrocyte of the hippocampus of rats in depression. Methods:The depression model was produced by separation and un-predicted mild stressors. The behavior was measured by open -field test.The rats acceived electric convulsive therapy(ECT) or modified electric convulsive therapy (MECT)treatment. The expression of cytokine receptor in neuron and astrocyte of the hippocampus was observed by the immunofluorescence detection technique. Results:There were significant differences among the stress and ECT group ,the stress and MECT group and the stress and shame-electroshock group in the two test. Conclusion:Both the ECT and the MECT treatment can promote the expression of cytokine receptor in neuron and astrocyte of the hippocampus of rats in depression. The cytokine(CK)may play an important role in the pathophysiological mechanism of depression. And the MECT treatment may be more effective than the ECT treatment.

gp130 is important for the normal morphogenesis of Meckel's cartilage and subsequent mandibular development

gp130-mediated signaling is involved in both chondrogenesis and osteogenesis, but its direct role in the formation of embryonic Meckel's cartilage and associated mandibular development has not yet been elucidated. In this study, we examined the influence of gp130 ablation on the developing mandibular Meckel's cartilage by evaluating the morphological and histological changes as well as the gene expression patterns in developing embryonic gp130-/- mice. The ablation of the gp130 gene showed no change in region-specific collagen mRNA expression except for a slight delay in its expression but caused shortened embryonic Meckel's cartilage, delayed hypertrophic chondrocyte maturation and subsequent bony replacement with characteristic bending of the intramandibular Meckel's cartilage. The bending of Meckel's cartilage led to a narrow mandibular arch at the rostral area with poor cortical plate formation. These findings indicate that gp130-mediated signaling is important for the normal morphogenesis of Meckel's cartilage and subsequent mandibular development.