1.Role of saliva proteinase 3 in dental caries.
Teng-Yu YANG ; Wen-Jie ZHOU ; Yue DU ; Song-Tao WU ; Wen-Wen YUAN ; Yu YU ; Lin SU ; Yang LUO ; Jie-Hua ZHANG ; Wan-Lu LU ; Xiao-Qian WANG ; Jiao CHEN ; Yun FENG ; Xue-Dong ZHOU ; Ping ZHANG
International Journal of Oral Science 2015;7(3):174-178
Salivary analysis can be used to assess the severity of caries. Of the known salivary proteins, a paucity of information exists concerning the role of proteinase 3 (PR3), a serine protease of the chymotrypsin family, in dental caries. Whole, unstimulated saliva was collected from children with varying degrees of active caries and tested using a Human Protease Array Kit and an enzyme-linked immunosorbent assay. A significantly decreased concentration of salivary PR3 was noted with increasing severity of dental caries (P<0.01); a positive correlation (r=0.87; P<0.01; Pearson's correlation analysis) was also observed between salivary pH and PR3 concentration. In an antibacterial test, a PR3 concentration of 250 ng·mL⁻¹ or higher significantly inhibited Streptococcus mutans UA159 growth after 12 h of incubation (P<0.05). These studies indicate that PR3 is a salivary factor associated with the severity of dental caries, as suggested by the negative relationship between salivary PR3 concentration and the severity of caries as well as the susceptibility of S. mutans to PR3.
Child
;
Dental Caries
;
enzymology
;
Female
;
Humans
;
Male
;
Myeloblastin
;
metabolism
;
Saliva
;
enzymology
2.Value of anti-neutrophil cytoplasmic antibody in assessing the severity of bronchiolitis obliterans in children.
Xiao-Wen CHEN ; De-Hui CHEN ; Shang-Zhi WU ; Na XIE ; Wen-Kuan LIU ; Yu-Neng LIN ; Ya-Wen ZHANG ; Qing-Si ZENG
Chinese Journal of Contemporary Pediatrics 2020;22(9):990-995
OBJECTIVE:
To study the value of anti-neutrophil cytoplasmic antibody (ANCA) in assessing the severity of bronchiolitis obliterans (BO) in children.
METHODS:
A prospective analysis was performed on 59 children who were diagnosed with BO from June 2009 to October 2014. ELISA was used to measure the concentrations of myeloperoxidase (MPO)-ANCA and proteinase 3 (PR3)-ANCA in serum. According to the results of ELISA, the children were divided into three groups: double-negative ANCA (n=22), single-positive ANCA (n=17), and double-positive ANCA (n=20). The three groups were compared in terms of the scores of BO risk factors, clinical symptoms, chest high-resolution computed tomography (HRCT), and lung pathology on admission, as well as the changes in the expression level of ANCA and the scores of clinical symptoms and chest HRCT over time.
RESULTS:
Compared with the double-negative ANCA group, the double-positive ANCA group had a significantly higher score of BO risk factors (P<0.05), and the single-positive ANCA group and the double-positive ANCA group had significantly higher scores of clinical symptoms, chest HRCT, and lung pathology (P<0.05). The children were followed up for 6 months after discharge, and there were significant reductions in MPO-ANCA and PR3-ANCA titers from admission and discharge to the end of follow-up (P<0.05), as well as a significant reduction in the score of clinical symptoms from admission to the end of follow-up (P<0.05), while there was no significant change in the score of chest HRCT from admission to the end of follow-up (P>0.05). The single-positive ANCA and double-positive ANCA groups still had a significantly higher score of clinical symptoms than the double-negative ANCA group (P<0.05).
CONCLUSIONS
The expression level of ANCA is correlated with the severity of BO in children and thus has certain clinical significance in disease evaluation.
Antibodies, Antineutrophil Cytoplasmic
;
Bronchiolitis Obliterans
;
Child
;
Humans
;
Myeloblastin
;
Peroxidase
;
Prospective Studies
3.Terminally Differentiating Eosinophils Express Neutrophil Primary Granule Proteins as well as Eosinophil-specific Granule Proteins in a Temporal Manner.
Karam KIM ; Sae Mi HWANG ; Sung Min KIM ; Sung Woo PARK ; Yunjae JUNG ; Il Yup CHUNG
Immune Network 2017;17(6):410-423
Neutrophils and eosinophils, 2 prominent granulocytes, are commonly derived from myelocytic progenitors through successive stages in the bone marrow. Our previous genome-wide transcriptomic data unexpectedly showed that genes encoding a multitude of neutrophil primary granule proteins (NPGPs) were markedly downregulated during the end period of eosinophilic terminal differentiation when cord blood (CB) cluster of differentiation (CD) 34+ cells were induced to differentiate toward the eosinophil lineage during a 24-day culture period. Accordingly, this study aimed to examine whether NPGP genes were expressed on the way to eosinophil terminal differentiation stage and to compare their expression kinetics with that of genes encoding eosinophil-specific granule proteins (ESGPs). Transcripts of all NPGP genes examined, including proteinase 3, myeloperoxidase, cathepsin G (CTSG), and neutrophil elastase, reached a peak at day 12 and sharply declined thereafter, while transcript of ESGP genes including major basic protein 1 (MBP1) attained maximum expression at days 18 or 24. Growth factor independent 1 (GFI1) and CCAAT/enhancer-binding protein α (C/EBPA), transactivators for the NPGP genes, were expressed immediately before the NPGP genes, whereas expression of C/EBPA, GATA1, and GATA2 kinetically paralleled that of eosinophil granule protein genes. The expression kinetics of NPGPs and ESGPs were duplicated upon differentiation of the eosinophilic leukemia cell line (EoL-1) immature eosinophilic cells. Importantly, confocal image analysis showed that CTSG was strongly coexpressed with MBP1 in differentiating CB eosinophils at days 12 and 18 and became barely detectable at day 24 and beyond. Our results suggest for the first time the presence of an immature stage where eosinophils coexpress NPGPs and ESGPs before final maturation.
Bone Marrow
;
Cathepsin G
;
Cell Line
;
Eosinophils*
;
Fetal Blood
;
Granulocytes
;
Hypereosinophilic Syndrome
;
Kinetics
;
Leukocyte Elastase
;
Myeloblastin
;
Neutrophils*
;
Peroxidase
;
Trans-Activators
4.Role of inflammasome activation in development and exacerbation of asthma
Tae Hyeong LEE ; Hyun Ji SONG ; Choon Sik PARK
Asia Pacific Allergy 2014;4(4):187-196
Human airways contact with pathogen-associated molecular patterns and danger-associated molecular patterns present in many environments. Asthmatic's airways may be more susceptible to these patterns and lead to inflammasome activation; however, the participation of inflammasome in the development and exacerbation of asthma is not fully understood and remains controversial. Asthma is a heterogeneous group composed of different airway inflammation patterns with different underlying immune mechanisms. One mechanism is neutrophilic airway inflammation based on the axis of inflammasome activation, interleukin (IL) 1β/IL-18 production, T helper 17 activation, IL-8/IL-6 overproduction, and neutrophilic inflammation. The role of inflammasome activation has been highlighted in experimental asthma models and some evidence of inflammasome activation has been recently demonstrated in human neutrophilic asthmatic airways. In addition to caspase-1 activation, proteinase 3 and other protease from activated neutrophils directly cleave pro-IL-1β and pro-IL-18 to IL-1β and IL-18, which contribute to the phenotype of subsequent adaptive immune responses without inflammasome activation. Data suggests that neutrophilics in asthmatic airways may have an additional effect in initiating inflammasome activation and amplifying immune responses. Among the mediators from neutrophils, S100A9 seems to be one candidate mediator to explain the action of neutrophils in amplifying the airway inflammation in concert with inflammasome.
Asthma
;
Calgranulin B
;
Humans
;
Inflammasomes
;
Inflammation
;
Interleukin-18
;
Interleukins
;
Myeloblastin
;
Neutrophils
;
Pathogen-Associated Molecular Pattern Molecules
;
Phenotype
;
Th17 Cells
5.Evaluation of diagnostic efficacy of digital liquid chip method for detection of specific antineutrophil cytoplasmic antibodies.
Li WANG ; Zhen Zhen SU ; Jing HU ; Zhuo Chun HUANG ; Xue Dan GAO ; Bin YANG
Chinese Journal of Preventive Medicine 2022;56(12):1850-1854
To explore the clinical diagnostic efficacy of antineutrophil cytoplasmic antibody associated vasculitis (AAV) by comparing the consistency and coincidence rate of serum anti-myeloperoxidase (MPO) antibody and anti-protease 3 (PR3) antibody detected by digital liquid chip method (DLCM) and enzyme-linked immunosorbent assay (ELISA). To provide reference for the selection of detection methods of anti-MPO antibody and anti-PR3 antibody in clinical laboratory. This study is a cross-sectional study, a total of 307 cases of antineutrophil cytoplasmic antibodies were detected in the Department of Clinical Immunology, West China Hospital of Sichuan University from January to March 2021. The serum samples and related clinical information were collected. At the same time, the levels of anti-MPO antibody and anti-PR3 antibody in serum samples were detected by ELISA and DLCM, indirect immunofluorescence (IIF) was used to re-test the differential samples between the two methods. SPSS 26.0 was used to analyze the test results, Cohen's kappa coefficient analysis was used to compare the consistency of the two methods, and paired chi-square test was used to compare the sensitivity and specificity of the two methods to AAV. The results showed that the positive cases of anti-MPO antibody detected by ELISA and DLCM were 63 and 44, and the negative cases were 244 and 263; the positive cases of anti-PR3 antibody detected by ELISA and DLCM were 34 and 28, and the negative cases were 273 and 279. The results of anti-MPO antibody and anti-PR3 antibody detected by the two methods had good consistency and coincidence rate, in which the total coincidence rate of anti-MPO antibody was 92.51%, the positive coincidence rate was 66.67%, and the negative coincidence rate was 99.18%. The results of consistency analysis showed that kappa=0.741 had well consistency. The total coincidence rate of anti-PR3 antibody is 96.74%, the positive coincidence rate is 76.47%, and the negative coincidence rate is 99.27%. The consistency analysis results show that kappa=0.821 had strong consistency. The results of IIF re-test of differential samples showed that the coincidence rate between DLCM and IIF was higher. The results of comparative analysis of anti-MPO antibody and anti-PR3 antibody showed that the specificity of DLCM was better than that of ELISA, and its sensitivity was lower than that of ELISA. In conclusion, the results of anti-MPO antibody and anti-PR3 antibody detected by DLCM were consistent with those of ELISA. In the combined detection of anti-MPO antibody and anti-PR3 antibody, the specificity of DLCM is better than that of ELISA.
Humans
;
Antibodies, Antineutrophil Cytoplasmic/analysis*
;
Myeloblastin
;
Cross-Sectional Studies
;
Sensitivity and Specificity
;
Fluorescent Antibody Technique, Indirect
;
Enzyme-Linked Immunosorbent Assay/methods*
6.IL-32-induced Inflammatory Cytokines Are Selectively Suppressed by α1-antitrypsin in Mouse Bone Marrow Cells.
Siyoung LEE ; Dong Ki CHOI ; Areum KWAK ; Sinae KIM ; Tam Thanh NGUYEN ; Gaae GIL ; Eunhye KIM ; Kwang Ha YOO ; In Ae KIM ; Youngmin LEE ; Hyunjhung JHUN ; Edward D CHAN ; Xiyuan BAI ; Hyunwoo KIM ; Yong Sung KIM ; Soohyun KIM
Immune Network 2017;17(2):116-120
The induction of interleukin (IL)-32 in bone marrow (BM) inflammation is crucial in graft versus host disease (GvHD) that is a common side effect of allogeneic BM transplantation. Clinical trials on α-1 antitrypsin (AAT) in patients with GvHD are based on the preliminary human and mouse studies on AAT reducing the severity of GvHD. Proteinase 3 (PR3) is an IL-32-binding protein that was isolated from human urine. IL-32 primarily induces inflammatory cytokines in myeloid cells, probably due to PR3 expression on the membrane of the myeloid lineage cells. The inhibitory activity of AAT on serine proteinases may explain the anti-inflammatory effect of AAT on GvHD. However, the anti-inflammatory activity of AAT on BM cells remains unclear. Mouse BM cells were treated with IL-32γ and different inflammatory stimuli to investigate the anti-inflammatory activity of AAT. Recombinant AAT-Fc fusion protein inhibited IL-32γ-induced IL-6 expression in BM cells, but failed to suppress that induced by other stimuli. In addition, the binding of IL-32γ to PR3 was abrogated by AAT-Fc. The data suggest that the specific anti-inflammatory effect of AAT in mouse BM cells is due to the blocking of IL-32 binding to membrane PR3.
Animals
;
Bone Marrow Cells*
;
Bone Marrow*
;
Cytokines*
;
Graft vs Host Disease
;
Humans
;
Inflammation
;
Interleukin-6
;
Interleukins
;
Membranes
;
Mice*
;
Myeloblastin
;
Myeloid Cells
;
Serine Proteases
7.Potential Role of Bacterial Infection in Autoimmune Diseases: A New Aspect of Molecular Mimicry.
Jehan ALAM ; Yong Chul KIM ; Youngnim CHOI
Immune Network 2014;14(1):7-13
Molecular mimicry is an attractive mechanism for triggering autoimmunity. In this review, we explore the potential role of evolutionary conserved bacterial proteins in the production of autoantibodies with focus on granulomatosis with polyangiitis (GPA) and rheumatoid arthritis (RA). Seven autoantigens characterized in GPA and RA were BLASTed against a bacterial protein database. Of the seven autoantigens, proteinase 3, type II collagen, binding immunoglobulin protein, glucose-6-phosphate isomerase, alpha-enolase, and heterogeneous nuclear ribonuclear protein have well-conserved bacterial orthologs. Importantly, those bacterial orthologs are also found in human-associated bacteria. The wide distribution of the highly conserved stress proteins or enzymes among the members of the normal flora and common infectious microorganisms raises a new question on how cross-reactive autoantibodies are not produced during the immune response to these bacteria in most healthy people. Understanding the mechanisms that deselect auto-reactive B cell clones during the germinal center reaction to homologous foreign antigens may provide a novel strategy to treat autoimmune diseases.
Arthritis, Rheumatoid
;
Autoantibodies
;
Autoantigens
;
Autoimmune Diseases*
;
Autoimmunity
;
Bacteria
;
Bacterial Infections*
;
Bacterial Proteins
;
Clone Cells
;
Collagen Type II
;
Germinal Center
;
Glucose-6-Phosphate Isomerase
;
Heat-Shock Proteins
;
Immunoglobulins
;
Molecular Mimicry*
;
Myeloblastin
;
Phosphopyruvate Hydratase
8.Clinical and pathological manifestations of patients with antineutrophil cytoplasmic autoantibodies directed against proteinase 3 or myeloperoxidase.
Xuan ZHANG ; Yi DONG ; Xiaofeng ZENG ; Yongzhe LI ; Fulin TANG
Chinese Medical Sciences Journal 2002;17(1):32-35
OBJECTIVETo compare the clinical and pathological manifestations of patients with antineutrophil cytoplasmic autoantibodies (ANCA) directed against proteinase 3 (anti-PR3) or myeloperoxidase (anti-MPO).
METHODSOne hundred and forty patients with ANCA were detected for anti-PR3 and anti-MPO by ELISA. The clinical features at presentation, histopathological characteristics and outcome of all patients who were tested positive for anti-PR3 or anti-MPO were analysed.
RESULTSIn anti-PR3 group (n = 21), 16 cases (76.2%) had systemic vasculitis, in which Wegener's granulomatosis prevailed (13 cases, 61.9%). In anti-MPO group (n = 31), 19 cases (61.3%) were diagnosed as systemic vasculitis and 12 cases (38.7%) as microscopic angiitis. For vasculitic patients with anti-PR3 and anti-MPO, the disease duration at diagnosis was 9.6 +/- 2.0 m and 4.4 +/- 0.9 m respectively, P < 0.05; vasculitis activity index (BVAS) and mean number of affected organ were 22.5 +/- 2.1, 5.0 +/- 0.4 and 25.1 +/- 1.7, 4.8 +/- 0.4 respectively, P > 0.05; upper respiratory tract, eye and joint involvements were 11(68.8%), 7(43.8%), 11(68.8%) and 7(36.8%), 2(10.5%), 5(26.3%) respectively, P < 0.05. Although there was no statistical difference in renal involvement between these two groups, patients with serum creatine > 500 micromol/L were more commonly seen in anti-MPO group than in anti-PR3 group, which were 8(42.1%) and 2(12.5%) respectively, P < 0.05. Ten relapses were seen in anti-PR3 group and only 2 in anti-MPO group, but the acute mortality rate in anti-MPO group (5/19, 27.4%) was much higher than that in anti-PR3 group (1/16, 6.3%).
CONCLUSIONSAnti-PR3 and anti-MPO occurred mainly in systemic vasculitis. A large divergence was seen in the disease spectrum between patients with anti-PR3 and those with anti-MPO. In particular, upper respiratory tract, eye and joint involvements, granuloma formation and relapse were more prominent in anti-PR3 patients. By contrast, the anti-MPO patients had a more acute disease onset, more rapid progressive renal involvement and a higher acute mortality rate.
Antibodies, Antineutrophil Cytoplasmic ; analysis ; Autoantibodies ; analysis ; Follow-Up Studies ; Granulomatosis with Polyangiitis ; drug therapy ; immunology ; pathology ; Humans ; Immunosuppressive Agents ; therapeutic use ; Kidney ; pathology ; Myeloblastin ; Peroxidase ; immunology ; Respiratory System ; pathology ; Serine Endopeptidases ; immunology ; Vasculitis ; drug therapy ; immunology ; pathology
9.Antineutrophil Cytoplasmic Antibody in Korean Children with Henoch-Schonlein Purpura.
Ji Na CHOI ; Jae Il SHIN ; Jae Seung LEE ; Hyon Suk KIM
Journal of the Korean Society of Pediatric Nephrology 2008;12(2):164-169
PURPOSE: There have been some reports on the prevalence of positive antineutrophil cytoplasmic antibody(ANCA) in Henoch-Schonlein purpura(HSP), but the results were conflicting. We performed this study to evaluate the clinical significance of ANCA(c-ANCA and p-ANCA) in Korean children with HSP. METHODS: The medical records of 30 patients(13 boys and 17 girls) aged 6.0+/-1.9(5-12) years with a clinical diagnosis of HSP based on the EULAR/PReS criteria were reviewed retrospectively. From the years 2007 to 2008, the sera from children with acute HSP were tested for antineutrophil cytoplasmic antibodies(ANCA). The target antigens of these autoantibodies are proteinase 3(c-ANCA) or myeloperoxidase(p-ANCA). RESULTS: Palpable purpura was seen in all 30 patients(100%), abdominal pain in 20(67%), arthralgia in 17(57%), and renal involvement in 11(37%). Laboratory findings showed leukocytosis in 4 patients(13%), thrombocytosis 18 in(60%), and elevated erythrocyte sedimentation rate in 18(60%). Anti-streptolysin O titers were elevated in 7% of the patients and no patient showed elevation of serum IgA level. The sera from 29 patients were negative for c-ANCA and p-ANCA by indirect immunofluorescence, but only one patient had weakly positive results, which became negative at follow-up. CONCLUSION: We conclude that c-ANCA or p-ANCA is not an important serologic marker in children with HSP, because it was neither diagnostically nor immunologically specific in children with HSP. These results suggest that ANCA are not involved in the pathogenesis of HSP in children.
Abdominal Pain
;
Aged
;
Antibodies, Antineutrophil Cytoplasmic
;
Arthralgia
;
Autoantibodies
;
Blood Sedimentation
;
Child
;
Cytoplasm
;
Fluorescent Antibody Technique, Indirect
;
Follow-Up Studies
;
Humans
;
Immunoglobulin A
;
Leukocytosis
;
Medical Records
;
Myeloblastin
;
Peroxidase
;
Prevalence
;
Purpura
;
Purpura, Schoenlein-Henoch
;
Retrospective Studies
;
Thrombocytosis
10.Clinical and pathological characterization of antineutrophil cytoplasmic antibody associated small vasculitis in children.
Jian-hua ZHOU ; Jin-hui TANG ; Hong SHI ; Tong-lin LIU ; Li-ru QIU ; Yu CHEN
Chinese Journal of Pediatrics 2004;42(6):408-411
OBJECTIVEAntineutrophil cytoplasmic antibody (ANCA) associated small vasculitides (ASV) are rare in children and often complicated in clinical manifestations and have very poor prognosis. In order to deepen our understanding of ANCA-associated small vasculitis (ASV) in children, the present study aimed to characterize their clinical manifestations, serum ANCA and renal histopathological findings and outcomes in Chinese children.
METHODSSerum ANCA was qualitatively tested with indirect immunofluorescence microscopy and anti-proteinase 3 (PR(3)) and anti-myeloperoxidase (MPO) activity were quantitated by enzyme-linked immunosorbent assays (ELISA), and renal biopsies were done to investigate the pathological changes. The clinical manifestation, serum ANCA and renal histopathological findings and outcome were characterized in 5 children with ANCA associated small vasculitis.
RESULTS(1) Five children with ANCA associated small vasculitis only accounted for 1.20% of children in whom renal biopsy was performed and 0.25% of hospitalized children with renal diseases during the same period. The age of onset of the 5 children with ASV was between 8 to 12 years with mean age 10.5 years. All ASV children were female. (2) All ASV children were negative for C-ANCA and showed normal anti-proteinase 3 activities, but positive for P-ANCA with high anti-myeloperoxidase activities between 98 to 242 kEU/L. The mean value of MPO-ANCA was 154.5 kEU/L (normal range < 12.7 kEU/L). (3) All ASV in the children was microscopic polyarteritis with wide-spread glomerular crescents formation and capillary tuft fibrinoid necrosis. Variety of complement C3 deposits and weak immunoglobulin deposits were noted in all ASV but one child who showed relatively strong deposits of IgA and IgM. The electronic dense deposits were mainly located in subendothelial space but were also found in the glomerular basement membrane in one child. (4) Three children with ASV died within one year after diagnosis, and two got remission and restored renal function after combined pulse therapy with methylprednisolone and cyclophosphamide (CTX), but remained to have hematuria and small amount of proteinuria after 1 and 5 year follow-up, respectively.
CONCLUSIONChildhood ASV was female and P-ANCA predominant, more vulnerable to progress to renal failure and poorer in prognosis than adult cases. Qualitative and quantitative ANCA measurement and renal biopsy were key to the diagnosis of ASV in children.
Antibodies, Antineutrophil Cytoplasmic ; blood ; Biopsy ; Child ; Enzyme-Linked Immunosorbent Assay ; Female ; Fluorescent Antibody Technique, Indirect ; Humans ; Kidney ; pathology ; Kidney Function Tests ; Myeloblastin ; Peroxidase ; metabolism ; Prognosis ; Renal Insufficiency ; etiology ; pathology ; Serine Endopeptidases ; metabolism ; Vasculitis ; blood ; complications ; therapy