The humoral immune response of B cells is the key to the protection of specific immunity, and immune aging reshapes its production and function. The decreased B cell immune function is an indicator of immune senescence. The impaired humoral immune function mediated by antibody secreted by B cells leads to a decline in the response of elderly individuals to the vaccine. These people are therefore more susceptible to infection and deterioration, and have a higher incidence of tumors and metabolic diseases. Activation-induced cytidine deaminase (AID) is an enzyme that triggers immunoglobulin class conversion recombination (CSR) and somatic high frequency mutation (SHM). It decreases during immune senescence and is considered to be a biomarker of decreased B cell function in aging mice and humans. Understanding the inherent defects of B-cell immune senescence and the regulation mechanism of AID in the aging process can provide new research ideas for the susceptibility, prevention and treatment of diseases in the elderly.
Animals ; Humans ; Mice ; Aging/metabolism* ; B-Lymphocytes/metabolism* ; Cytidine Deaminase/metabolism* ; Somatic Hypermutation, Immunoglobulin

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with dyschromatosis symmetrica hereditaria (DSH). METHODS: PCR and Sanger sequencing were carried out for the proband, and suspected variant was validated by Sanger sequencing in the pedigree. RESULTS: The proband was found to harbor a novel variant of c.1352delA (p.N451Mfs*13) of the ADAR (NM_001111) gene. The same variant was found in her affected mother and sister, but not in her unaffected father, uncle, and 100 healthy individual. CONCLUSION The novel variant of the ADAR gene probably underlay the pathogenesis of DSH in this pedigree.
Adenosine Deaminase/genetics* ; China ; Female ; Humans ; Mutation ; Pedigree ; Pigmentation Disorders/congenital* ; RNA-Binding Proteins/genetics*

OBJECTIVE: To analyze the clinical features and genetic basis for a Chinese pedigree affected with hereditary dyschromatosis symmetrica hereditaria (DSH). METHODS: Peripheral blood samples of the proband and his mother were collected and subjected to PCR and Sanger sequencing. RESULTS: The patient has conformed to the typical pattern of DSH and manifested with hyperpigmentation, hypo- and hyperpigmentation spots on the back of hands, feet and face. Sanger sequencing confirmed that the proband and his mother have both harbored heterozygous splicing variant c.2762+1G>T in exon 9 of the ADAR gene, which was unreported previously. The same variant was not detected among 100 healthy controls. According to the guidelines of the American College of Medical Genetics and Genomics, the variant was predicted to be pathogenic (PVS1+PM2+PP4). CONCLUSION The c.2762+1G>T variant of the ADAR gene probably underlay the DSH in this pedigree. Above finding has enriched the spectrum of ADAR gene mutations.
Adenosine Deaminase/genetics* ; China ; Humans ; Mutation ; Pedigree ; Pigmentation Disorders/congenital* ; RNA-Binding Proteins/genetics*

OBJECTIVE: To investigate the auxiliary diagnostic value of serum adenosine deaminase (ADA) in acute leukemia (AL) at clinical test. METHODS: 123 AL patients hospitalized in Zhejiang hospital from November 2018 to March 2020 were enrolled as the observation group, and 98 healthy people in the same period were randomly enrolled as the control group. AL patients were divided into two groups: 77 acute myeloid leukemia (AML) patients for AML group and 46 acute lymphoblastic leukemia (ALL) patients for ALL group. The levels of adenosine deaminase (ADA), alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH) and homocysteine (Hcy) in serum of the patients were detected, and the correlation of ADA with these items was analyzed. Receiver operating characteristic curve (ROC) was used to analyze the clinical diagnostic value of ADA, Yoden index was used to confirm the best cut-off point. RESULTS: The serum ADA level in AL patients was significant higher than that in control group (P < 0.05). The results of Pearson correlation analysis showed that there was a significant positive correlation of ADA with Hcy, ALT, AST, GGT, LDH in AML group (r = 0.47, r = 0.28, r = 0.37, r = 0.22, r = 0.55); and also there was a significant positive correlation of ADA with GGT in ALL group (r = 0.54). In AML group, the maximum area under ROC curve was 0.761 (P = 0.00), 95% confidence interval was 0.682-0.841, sensitivity was 54.50%, specificity was 98.90%, and the best cut-off point was 17.1 U/L. In ALL group, the maximum area under ROC curve was 0.785, 95% confidence interval was 0.694-0.877, sensitivity was 65.90%, specificity was 84.00%, and the best cut-off point was 13.45 U/L. CONCLUSION The detection of ADA in serum can be used as an auxiliary examination in patients with AL, which can provide a certain value for the diagnosis of the disease.
Adenosine Deaminase ; Humans ; L-Lactate Dehydrogenase ; Leukemia, Myeloid, Acute/diagnosis* ; ROC Curve ; Retrospective Studies

OBJECTIVE: To detect variants of ADAR1 gene in two Chinese pedigrees affected with dyschromatosis symmetrica hereditaria (DSH). METHODS: Clinical data and peripheral blood samples of the pedigrees were collected. All exons of the ADAR1 gene were amplified by PCR and subjected to Sanger sequencing. Suspected pathogenic variants were validated among other members of the pedigrees and 100 unrelated healthy controls. RESULTS: For pedigree 1, Sanger sequencing has identified a heterozygous missense variant c.3002G>C (p.Asp968His) in exon 11 of the ADAR1 gene in the proband and his father. For pedigree 2, a novel nonsense variant c.3145C>T (p.Gln1049Ter) was identified in exon 12 of the ADAR1 gene in the proband and his son, which were previously unreported and absent among the healthy controls. CONCLUSION The c.3002G>C (p.Asp968His) and c.3145C>T (p.Gln1049Ter)variants of the ADAR1 gene probably underlay the DSH in the two pedigrees.
Adenosine Deaminase/genetics* ; Humans ; Mutation ; Pedigree ; Pigmentation Disorders/genetics* ; RNA-Binding Proteins/genetics*

PURPOSE: In the present study, human neural stem cells (hNSCs) with tumor-tropic behavior were used as drug delivery vehicle to selectively target melanoma. A hNSC line (HB1.F3) was transduced into two types: one expressed only the cytosine deaminase (CD) gene (HB1.F3. CD) and the other expressed both CD and human interferon-β (IFN-β) genes (HB1.F3.CD. IFN-β). MATERIALS AND METHODS: This study verified the tumor-tropic migratory competence of engineered hNSCs on melanoma (A375SM) using a modified Boyden chamber assay in vitro and CM-DiI staining in vivo. The antitumor effect of HB1.F3.CD and HB1.F3.CD.IFN-β on melanoma was also confirmed using an MTT assay in vitro and xenograft mouse models. RESULTS: A secreted form of IFN-β from the HB1.F3.CD.IFN-β cells modified the epithelial-mesenchymal transition (EMT) process and metastasis of melanoma. 5-Fluorouracil treatment also accelerated the expression of the pro-apoptotic protein BAX and decelerated the expression of the anti-apoptotic protein Bcl-xL on melanoma cell line. CONCLUSION: Our results illustrate that engineered hNSCs prevented malignant melanoma cells from proliferating in the presence of the prodrug, and the form that secreted IFN-β intervened in the EMT process and melanoma metastasis. Hence, neural stem cell-directed enzyme/prodrug therapy is a plausible treatment for malignant melanoma.
Animals ; Cell Line ; Cytosine Deaminase ; Epithelial-Mesenchymal Transition ; Flucytosine ; Fluorouracil ; Heterografts ; Humans ; In Vitro Techniques ; Melanoma ; Mental Competency ; Mice ; Neoplasm Metastasis ; Neural Stem Cells ; Stem Cells

OBJECTIVE: To detect mutations of ADAR gene in two pedigrees affected with dyschromatosis symmetrica hereditaria (DSH). METHODS: Potential mutations of the ADAR gene were analyzed by Sanger sequencing of the probands from both pedigrees. Suspected mutations were validated by Sanger sequencing of other patients from both pedigrees as well as unrelated healthy individuals. RESULTS: A heterozygous nonsense mutation c.1325C>G (p.Ser442Ter) and a novel nonsense mutation c.1498C>T (p.Gln500Ter) were respectively identified in the ADAR gene among all patients from the two pedigrees but not among 200 healthy individuals. CONCLUSION Mutations of the ADAR gene probably underlie the DSH in the two pedigrees. Above findings have enriched the spectrum of ADAR gene mutation.
Adenosine Deaminase ; Humans ; Mutation ; Pedigree ; Pigmentation Disorders ; congenital ; genetics ; RNA-Binding Proteins

Adenosine ; genetics ; Adenosine Deaminase ; genetics ; metabolism ; Animals ; CRISPR-Associated Protein 9 ; genetics ; metabolism ; CRISPR-Cas Systems ; genetics ; Embryo, Mammalian ; metabolism ; Gene Editing ; Genetic Variation ; genetics ; Mice ; Mice, Inbred C57BL ; Rats ; Rats, Sprague-Dawley

RNA editing, especially A-to-I RNA editing, is a common post-transcriptional modification in mammals. Adenosine deaminase acting on RNA (ADAR) is a key protein for A-to-I editing, which converts the adenosine group of a double-stranded RNA to creatinine group by deaminating it, resulting in a change of nucleotide sequence. There are 3 types of ADARs (ADAR1, ADAR2, ADAR3) that have been found in recent years. The abnormalities of ADARs are closely related to many human diseases such as viral infections, metabolic diseases, nervous system diseases, and tumors.
Adenosine ; metabolism ; Adenosine Deaminase ; physiology ; Base Sequence ; Creatinine ; metabolism ; Deamination ; Disease ; etiology ; Humans ; RNA Editing ; physiology ; RNA, Double-Stranded ; RNA-Binding Proteins ; physiology

OBJECTIVE: Interleukin (IL)-17 is a pro-inflammatory cytokine that has pleiotropic effects on multiple target cells and thereby contributes to the development of immune-mediated inflammatory disorders. However, the role of IL-17 in the humoral immune response has not been clearly elucidated. METHODS: Mice deficient in IL-17A (IL-17A knockout [KO] mice) and wild type (WT) C57BL/6 mice were compared. Distinct B cell (mature/precursor and marginal zone/follicular) and plasma cell populations were compared using fluorescence-activated cell sorting (FACS) and confocal immunostaining. Immunoglobulin production was assessed by enzyme-linked immunosorbent assay. RESULTS: There was no difference in B cell and plasma cell populations between IL-17A KO and WT mice. However, after T cell-dependent antigen challenge, IL-17A KO mice produced lower levels of immunoglobulin (Ig)G1 than wild-type animals. IL-17A KO mice also showed reduced germinal center (GC) formation and lower expression of activation-induced cytidine deaminase, the essential enzyme for class switch recombination (CSR). IL-17 had no effect on the proliferation or survival of naïve B cells in in vitro functional studies. However, IL-17 treatment promoted naïve B cell differentiation into plasma cells in synergy with IL-4, although IL-17 alone had no effect. CONCLUSION: Our findings suggest that IL-17 contributes to the humoral immune response by enhancing GC formation, CSR to IgG1, and plasma cell differentiation in synergy with IL-4.
Animals ; B-Lymphocytes ; Cell Differentiation ; Cytidine Deaminase ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Germinal Center* ; Immunity, Humoral ; Immunoglobulin G ; Immunoglobulins* ; In Vitro Techniques ; Interleukin-17* ; Interleukin-4 ; Interleukins ; Mice* ; Plasma Cells ; Recombination, Genetic