Abstract　　B cell maturation antigen (BCMA) is an ideal target for precise treatment due to its highly selective expression on malignant myeloma cells. This review summarizes briefly the advances in the latest research progress on biological activity of BCMA, its significance as a biomarker and immunotherapy direcited against BCMA, such as bispecific antibodies, antibody drug conjugates, chimeric antigen receptor T cell therapy against mature B cell antigens.
Antigens, Differentiation, B-Lymphocyte ; B-Cell Maturation Antigen ; B-Lymphocytes ; Humans ; Immunotherapy ; Multiple Myeloma ; therapy ; T-Lymphocytes

<b>OBJECTIVEb>To investigate the effect of SAHA on the maturation of human dendritic cells (DC) and to explore its underlying mechanism.

<b>METHODSb>Peripheral blood mononuclear cells (PBMNC) were isolated from human peripheral blood and cultured in RPMI 1640 medium with 100 ng/ml rhGM-CSF and 500 U/ml rhIL-4. In the LPS induced maturation process, dendritic cells treated with or without SAHA were used as test group, and dendritic cells treated without LPS or SAHA were used as control group. DC was observed under inverted microscope. Flow cytometer was used to detect the surface antigen molecules expressed by DC. The mixed lymphocyte culture (MLC) was used to observe the allogeneic lymphocyte stimulation. The NF-κB signaling pathway was detected by electrophoretic mobility shift assay (EMSA).

<b>RESULTSb>The SAHA could effectively suppress the maturation of DC induced by LPS, the DC treated with SAHA+LPS had immature morphological characteristics; the expression of CD80, CD83 and HLA-DR in SAHA+LPS group and control group were significantly down-regulated as compared with single LPS group (P<0.01); the ability of DC to stimulate the proliferation of allogeneic T lymphocytes in SAHA+LPS group and control group was significantly weaker than that in single LPS group (P<0.01); EMSA results showed that NF-κB activity decreased after SAHA and LPS treatment and was significantly lower than that of single LPS group.

<b>CONCLUSIONb>SAHA can effectively suppress DC maturation induced by LPS and also weaken the ability to stimulate allogeneic T lymphocyte. NF-κB signaling pathway is involved in regulating DC maturation.

Cell Differentiation ; Dendritic Cells ; Flow Cytometry ; HLA-DR Antigens ; Humans ; Lymphocyte Activation ; Lymphocyte Culture Test, Mixed ; NF-kappa B ; T-Lymphocytes

BACKGROUND: Specimens for the external quality assessment (EQA) need to be highly stable during the EQA process. Therefore, we evaluated the stability of pooled sera (PS) for tumor markers including alpha fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA 125), and carbohydrate antigen 19-9 (CA 19-9). METHODS: PS with 2 different levels (high and low) of each of the 4 tumor markers were collected and stored at -20degrees C, 4degrees C, and room temperature (RT). The concentration of each tumor marker was then measured after storage under these different conditions at baseline and on days 1, 3, 7, 14, 30, 90, and 181. Internal quality control (QC) results during the evaluation period were also analyzed. RESULTS: Irrespective of storage conditions, coefficients of variation (CVs) of AFP and CA 125 levels in the PS during the evaluation period ranged from 3.3% to 7.5% in EQA assays and were similar to the CVs of QC assays. However, the levels of CEA detected in PS stored at -20degrees C, and 4degrees C, showed higher variability, with CVs ranging from 4.0% to 10.4%, and samples stored at RT showed especially high CVs, i.e., >8.3%. Samples for CA 19-9 testing stored at RT also showed lower stability than the QC samples as well as samples stored at -20degrees C, after 3 days. CONCLUSIONS: CEA and CA 19-9 levels in PS showed higher variability than AFP and CA 125, especially when stored at RT. These results indicate that all EQA specimens for tumor marker assays need to be tested as soon as possible and not stored at RT for longer than 3 days during the EQA process.
alpha-Fetoproteins ; Carcinoembryonic Antigen ; Quality Control ; Biomarkers, Tumor

Idiopathic thrombocytopenia purpura (ITP) is an autoimmune disease which is characterized by destruction of platelets by macrophages in the reticuloendothelial system. Recent studies suggest that ITP is related to the abnormal activation and apoptosis of T/B cells which lead to failure of immune tolerance. Now it is becoming clear that costimulatory signals are required for full T/B cell activation and assumed to modulate T/B cells responses as well as other aspects of the immune system. This review focuses on the role and state-of-the-art advancements of costimulatory signals in ITP.
Antigens, CD ; immunology ; Antigens, Differentiation ; immunology ; Antigens, Differentiation, T-Lymphocyte ; immunology ; B-Lymphocytes ; immunology ; CD28 Antigens ; immunology ; CTLA-4 Antigen ; Humans ; Immune Tolerance ; Inducible T-Cell Co-Stimulator Protein ; Purpura, Thrombocytopenic, Idiopathic ; immunology ; Receptors, Tumor Necrosis Factor ; immunology ; Signal Transduction ; physiology ; T-Lymphocytes ; immunology ; physiology

This study was purposed to investigate the clinical significance of the amount and activated status of T cell subsets, B cells, NK cells in peripheral blood from patients with myelodysplastic syndrome (MDS). The proportion of T cells, B cells, NK cells in peripheral blood from 30 patients with MDS and their surface activation markers of CD28, CD45RA, CD45RO, CD69, HLA-DR were analyzed by flow cytometry. Twenty-two patients were in the low risk group (RA + RAS) while eight patients were in the high risk group (RAEB + RAEBT). The result showed that the amounts of T cells (CD3+ cells) in peripheral blood from patients with MDS were lower than those in control group. The amounts of naive CD4+ cells (CD4+ CD45RA+ cells) in MDS patients were lower than those in control. The expression rates of early activation marker (CD69) and late activation marker (HLA-DR) on CD3+ cells in MDS patients were significantly higher than those in control. The abnormalities of the immunologically competent cells were mainly observed in the low risk group (RA + RAS), and were characterized by the high expression rates of CD69+ and HLA-DR+ on CD3+ cells, the decrease of B cell amounts. The amount abnormalities of T cell subsets were mainly observed in high risk group (RAEB + RAEBT), and were characterized by the decrease of CD3+ cells and CD3+ CD4+ CD8- cells (Th cells) amounts without high expression of the CD69 and HLA-DR, the decrease of NK cells amounts. It is concluded that there are the abnormalities of T cell subsets and function in the patients with MDS and may change with disease progression, so the measurement of amount and activated status of T cell subsets in peripheral blood from MDS patients can have predictive role for diagnosis of disease progression and guide of therapy.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antigens, CD ; immunology ; Antigens, Differentiation, T-Lymphocyte ; immunology ; B-Lymphocytes ; immunology ; CD3 Complex ; immunology ; Female ; HLA-DR Antigens ; immunology ; Humans ; Killer Cells, Natural ; immunology ; Lectins, C-Type ; Lymphocyte Activation ; immunology ; Male ; Middle Aged ; Myelodysplastic Syndromes ; immunology ; T-Lymphocyte Subsets ; immunology

BACKGROUND: Tumor markers are used for diagnosing cancers and monitoring responses to cancer therapy. In this study, we evaluated the performance of Lumipulse G1200 (Fujirebio, Japan), a fully automated serum analyzer, for immunoassays of tumor markers. METHODS: We determined the precision and linearity of assays performed using Lumipulse G1200 and the correlation between the results of this and other analyzers used for tumor markers according to the guidelines of the Clinical and Laboratory Standards Institute (CLSI). We used 9 tumor markers, namely, carcinoembryonic antigen, alpha-fetoprotein, cancer antigen 125, cancer antigen 15-3 (CA 15-3), cancer antigen 19-9, prostate specific antigen, protein induced by vitamin K absence or antagonist-II, and pepsinogens I and II. Further, we validated reference intervals using 20 serum samples of healthy individuals. RESULTS: Lumipulse G1200 yielded acceptable precision with total CV< or =5% and within-run CV< or =3% for all markers. Total CV for all markers was 2.4-3.7%, with the exception of CA 15-3 and pepsinogens I and II (CV, 4.0-5.0%). Linearity was observed for all markers over the entire analytical range. Results of Lumipulse G1200 were in good agreement with those of currently used analyzers with correlation coefficients>0.975 for all markers, except pepsinogen I (0.9569). The reference intervals provided by the manufacturer met the criteria mentioned in the CLSI guideline. CONCLUSIONS: Assays using Lumipulse G1200 had high precision, clinically acceptable linearity, and good correlation with the established assays. This indicates that Lumipulse G1200 can be potentially used in routine laboratories.
alpha-Fetoproteins ; Carcinoembryonic Antigen ; Immunoassay ; Pepsinogen A ; Pepsinogens ; Prostate-Specific Antigen ; Biomarkers, Tumor ; Vitamin K

BACKGROUND: Tumor markers are used for diagnosing cancers and monitoring responses to cancer therapy. In this study, we evaluated the performance of Lumipulse G1200 (Fujirebio, Japan), a fully automated serum analyzer, for immunoassays of tumor markers. METHODS: We determined the precision and linearity of assays performed using Lumipulse G1200 and the correlation between the results of this and other analyzers used for tumor markers according to the guidelines of the Clinical and Laboratory Standards Institute (CLSI). We used 9 tumor markers, namely, carcinoembryonic antigen, alpha-fetoprotein, cancer antigen 125, cancer antigen 15-3 (CA 15-3), cancer antigen 19-9, prostate specific antigen, protein induced by vitamin K absence or antagonist-II, and pepsinogens I and II. Further, we validated reference intervals using 20 serum samples of healthy individuals. RESULTS: Lumipulse G1200 yielded acceptable precision with total CV< or =5% and within-run CV< or =3% for all markers. Total CV for all markers was 2.4-3.7%, with the exception of CA 15-3 and pepsinogens I and II (CV, 4.0-5.0%). Linearity was observed for all markers over the entire analytical range. Results of Lumipulse G1200 were in good agreement with those of currently used analyzers with correlation coefficients>0.975 for all markers, except pepsinogen I (0.9569). The reference intervals provided by the manufacturer met the criteria mentioned in the CLSI guideline. CONCLUSIONS: Assays using Lumipulse G1200 had high precision, clinically acceptable linearity, and good correlation with the established assays. This indicates that Lumipulse G1200 can be potentially used in routine laboratories.
alpha-Fetoproteins ; Carcinoembryonic Antigen ; Immunoassay ; Pepsinogen A ; Pepsinogens ; Prostate-Specific Antigen ; Biomarkers, Tumor ; Vitamin K

In 2017, the tumor marker program of the Korean Association of External Quality Assessment Service was performed for tumor markers I and II. Tumor marker I comprised alpha-fetoprotein (AFP), carcinoembryonic antigen, protein induced by vitamin K absence-II, and prostate specific antigen (PSA), and tumor marker II comprised cancer antigen (CA) 125, CA 19-9, CA 15-3, CA 72-4, and beta-2-microglobulin. Two challenges were conducted with three pooled serum or control materials, except for the first tumor marker I challenge. In total, 648 institutions participated in tumor marker I and 380 in tumor marker II programs. The response rates were 92.9%–97.0%. The coefficients of variation (CVs) were different depending on tests and samples, and average CVs were 3.7%–16.8%. The average CV of CA 72-4 tests, whose number of participants was the smallest, was the lowest. The average CV of AFP tests, which included a sample with very high levels, was the highest.
alpha-Fetoproteins ; Biomarkers, Tumor* ; Carcinoembryonic Antigen ; Korea* ; Prostate-Specific Antigen ; Vitamin K

<b>OBJECTIVEb>To study activation of dendritic cells (DC) isolated from peripheral blood monocytes of patients with chronic hepatitis B after stimulation with HBsAg or HBcAg.

<b>METHODSb>DCs were isolated from peripheral blood monocytes of patients with chronic hepatitis B. DCs were impulsed with HBsAg and HBcAg separately before their maturation. The expression levels of DC surface molecule were analyzed by using flow cytometry and the ability of DC to induce T lymphocyte proliferation was evaluated by a liquid scintillation counter and the amount of interleukin-12 (IL-12) in mixed lymphocytic (IL-12) in mixed lymphocytic reaction (MLR) was measured by using ELISA.

<b>RESULTSb>The expression rate of CD86 significantly increased to (29.20 +/- 5.18)% on DC after loading with HBcAg as compared with those after loading with HBsAg (76.19 +/- 3.90)% and controls (62.37 +/- 4.24)%, P>0.01. The ability of DC after loading with HBcAg to induce T lymphocyte proliferation (34,326 +/- 3088 cpm) was significantly higher than that of DC after loading with HBsAg (20,306 +/- 2897 cpm) and controls (3454 +/- 409 cpm), P greater than 0.01. The amount of IL-12 in MLR of DC after loading with HBcAg was (348 +/- 42.8) ng/L, which was significantly higher than those of DC after loading with HBsAg (226 +/- 30.6) ng/L and controls (116 +/- 15.6) ng/L, P greater than 0.01.

<b>CONCLUSIONb>Human dendritic cell stimulated with HBcAg could more efficiently present antigen and induce specific T cell immune response.

Adult ; Antigens, CD ; metabolism ; Antigens, Differentiation, Myelomonocytic ; metabolism ; Cell Proliferation ; Dendritic Cells ; cytology ; immunology ; metabolism ; Female ; Flow Cytometry ; Hepatitis B Core Antigens ; immunology ; Hepatitis B Surface Antigens ; immunology ; Hepatitis B, Chronic ; blood ; virology ; Humans ; Lymphocyte Activation ; immunology ; Male ; Middle Aged ; T-Lymphocytes ; cytology ; immunology ; Young Adult

Objective: To compare insulin surrogate indices with the homeostasis model assessment of insulin resistance (HOMA-IR) in Thai people with type 2 diabetes (T2D). Methodology: A cross-sectional study of 97 individuals with T2D was done to determine the association between HOMA-IR and seven surrogate indices for insulin resistance. IR was defined as HOMA-IR ≥2.0. The indices included Waist Circumference (WC), Waist-to-Hip Ratio (WHR), Waist-to-Height Ratio (WHtR), Triglyceride-Glucose (TyG) index, estimated Glucose Disposal Rate (eGDR) calculated by WC, BMI, and WHR. Results: A total of 97 subjects with T2D (36.1% female, mean age 61.7 ± 12.0 years, BMI 26.4 ± 3.7 kg/m2, A1C 6.9 ± 1.2%) were studied. The TyG index showed a positive association with HOMA-IR, while eGDR exhibited a negative association. TyG index had the strongest correlation with IR (r = 0.49), while various eGDR formulas showed weaker negative correlations (r = 0.12-0.25). However, subgroup analysis in individuals with T2D and coronary artery disease (CAD) showed that only eGDR-WC and eGDR-BMI demonstrated a significant correlation with triple vessel disease. Conclusion The TyG index was a useful and simple marker for identifying the presence of IR in Thai people with T2D. Future longitudinal studies are warranted to demonstrate the prediction value of cardiovascular outcomes.
Insulin Resistance ; Surrogate Markers ; Biomarkers