scholarly journals Elevated Myeloperoxidase-DNA Complex Levels in Sera of Patients with IgA Vasculitis

Pathobiology ◽  
2021 ◽  
pp. 1-6
Author(s):  
Sora Takeuchi ◽  
Tamihiro Kawakami ◽  
Tatsuro Okano ◽  
Haruki Shida ◽  
Daigo Nakazawa ◽  
...  
Keyword(s):  
Systemic Disease ◽  
Serum Levels ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Enzyme Linked Immunosorbent Assay ◽  
Clinical Parameters ◽  
Iga Vasculitis ◽  
Extracellular Traps ◽  
Anca Associated Vasculitis ◽  
Serum Iga ◽  
Dna Complex

<b><i>Introduction:</i></b> IgA vasculitis is a systemic disease that results from the entrapment of circulating IgA-containing immune complexes in small-vessel walls in the skin, kidneys, and gastrointestinal tract. An excessive formation of neutrophil extracellular traps (NETs) is involved in the pathogenesis of vasculitis, especially in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. This study aimed to clarify whether NETs are implicated in IgA vasculitis. <b><i>Methods:</i></b> Twenty-two patients with IgA vasculitis and 4 healthy volunteers were enrolled in this study. Serum levels of myeloperoxidase (MPO)-DNA complex, a fragment derived from NETs, were determined by enzyme-linked immunosorbent assay (ELISA), and the association between MPO-DNA complex levels and clinical parameters was examined. The presence of the ANCA was also assessed by ELISA specific for MPO and proteinase 3 (PR3) and indirect immunofluorescence (IIF), followed by assessing the differences in clinical parameters with and without the ANCA. <b><i>Results:</i></b> Serum MPO-DNA complex levels were significantly higher in patients with IgA vasculitis than those in healthy controls. A significant positive correlation between the serum MPO-DNA complex and IgA levels was noted. Interestingly, 63.6% of IgA vasculitis patients were ANCA-positive in IIF with an atypical pattern, whereas neither MPO-ANCA nor PR3-ANCA was detected by ELISA. These findings indicated that some IgA vasculitis patients possessed the so called minor ANCA. Serum IgA and MPO-DNA complex levels and the frequency of hematuria in the minor ANCA-positive group were significantly higher than in the minor ANCA-negative group. <b><i>Conclusion:</i></b> The collective findings suggested that NETs are certainly involved in the pathogenesis of IgA vasculitis.

scholarly journals Anti-phosphatidylserine/prothrombin Complex Antibodies in Patients With Cutaneous Vasculitis: Possible Involvement in the Pathogenesis

2020 ◽  
Author(s):  
Yuto Tamura ◽  
Tamihiro Kawakami ◽  
Yupeng Dong ◽  
Miku Yoshinari ◽  
Yuka Nishibata ◽  
...  
Keyword(s):  
Vascular Endothelium ◽  
Systemic Vasculitis ◽  
Serum Levels ◽  
Cutaneous Vasculitis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Iga Vasculitis ◽  
Skin Involvement ◽  
Wild Type ◽  
Significant Difference

Abstract Objective. It was previously demonstrated that cutaneous vasculitis, including IgA vasculitis and cutaneous arteritis (CA), is associated with the presence of IgM antibodies (Abs) against the phosphatidylserine/prothrombin complex (PS/PT). Recently, novel enzyme-linked immunosorbent assay kits for the detection of IgG and IgM anti-PS/PT (aPS/PT) Abs have become commercially available.Methods. The prevalence of serum IgG and IgM aPS/PT Abs in both cutaneous and systemic vasculitis was determined using these kits. In addition, to examine whether aPS/PT Abs were involved in the pathogenesis of cutaneous vasculitis, inbred wild-type rats were intravenously administered with a rat IgM class aPS/PT monoclonal Ab established previously or with rat immunoglobulins as controls. To express PS on the surface of vascular endothelium, these rats were given a subcutaneous injection of cell-free histones (250 µg/ml, 300 µl/site) 2 hours in advance. Results. Serum IgM aPS/PT Ab levels were elevated in patients with systemic vasculitis with skin involvement and CA compared to those in patients with systemic vasculitis without skin involvement and healthy controls. There was no significant difference in the serum levels of IgG aPS/PT Abs between the patients and healthy controls. Correspondingly, inbred wild-type rats intravenously administered with the aPS/PT monoclonal IgM Ab after appropriate priming—subcutaneous histone injection—developed cutaneous vasculitis. Some rats given rat IgM instead of the aPS/PT monoclonal Ab also developed cutaneous vasculitis, whereas vasculitis did not occur in rats given IgG or only priming by histones. Conclusion. IgM aPS/PT Abs could be involved in the pathogenesis of cutaneous vasculitis.

scholarly journals Apolipoprotein M Serum Levels Correlate with IgA Vasculitis and IgA Vasculitis Nephritis

2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Jiali Wu ◽  
Lagu He ◽  
Le Bai ◽  
Li Tan ◽  
Min Hu
Keyword(s):  
Protective Factor ◽  
Serum Levels ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Iga Vasculitis ◽  
Independent Predictive Factor ◽  
Apolipoprotein M ◽  
Biochemical Analyzer ◽  
And Gender ◽  
Study Participants

Objective. IgA vasculitis (lgAV) is the most frequent vessel vasculitis in children, and the prognosis is related to the children’s age and degree of nephritis. This study is aimed at investigating serum apolipoprotein M (apoM) levels in patients with lgAV patients and at evaluating the association between apoM and disease severity. Methods. A total of 109 lgAV patients and 76 age- and sex-matched healthy controls were included. The age and gender of the study participants were matched. ApoM levels were measured by an enzyme-linked immunosorbent assay. Additionally, the serum levels of lipids, apolipoproteins, kidney biochemical profiles, immunoglobulins (IgA, IgG, IgM, and IgE), and the complements (C3 and C4) were assessed using an automatic biochemical analyzer. Results. ApoM was increased significantly in lgAV patients compared to healthy controls. ApoM, meanwhile, was lower in patients with nephritis than in those without nephritis. The apoM levels were higher in classes I and II IgA vasculitis nephritis (lgAVN) patients than in classes III and IV. Besides, the apoM serum level<24.81 mg/L was an independent predictive factor for lgAVN and can be independently associated with the presence of nephritis in lgAV patients. Meanwhile, the serum apoM concentration negatively correlated with the ISKDC grading score in lgAVN patients. Conclusions. Serum apoM was elevated in lgAV patients and decreased gradually with the ISKDC grading score. ApoM (OR=0.32, 95%CI=0.12‐0.85, p=0.023) was identified as a protective factor for nephritis in all lgAV patients.

Microparticles Expressing Myeloperoxidase and Complement C3a and C5a as Markers of Renal Involvement in Antineutrophil Cytoplasmic Antibody–associated Vasculitis

2019 ◽  
Vol 47 (5) ◽  
pp. 714-721 ◽  
Author(s):  
Aleksandra Antovic ◽  
Fariborz Mobarrez ◽  
Milena Manojlovic ◽  
Nida Soutari ◽  
Victoria De Porta Baggemar ◽  
...  
Keyword(s):  
Disease Activity ◽  
Renal Involvement ◽  
Serum Levels ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Birmingham Vasculitis Activity Score ◽  
Complement Components ◽  
Anca Associated Vasculitis ◽  
Terminal Complement ◽  
Active Disease

Objective.To investigate expression of terminal complement components C3a and C5a on circulating myeloperoxidase (MPO)-positive microparticles (MPO+MP) in relation to disease activity and renal involvement in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).Methods.Forty-six clinically well-characterized patients with AAV and 23 age- and sex-matched healthy controls were included. The concentration of MPO+MP expressing C3a and C5a was analyzed from citrate plasma by flow cytometry. Serum levels of C3a and C5a were determined using commercial ELISA. The assessment of vasculitis disease activity was performed using the Birmingham Vasculitis Activity Score (BVAS). Among patients, 23 had active disease with BVAS ≥ 2 and 14 patients had active renal flares.Results.AAV patients had significantly increased expression of C3a and C5a on MPO+MP compared to controls (both p < 0.0001). When the group of patients with active AAV was divided according to the presence of renal activity, the concentration of MPO+MP expressing C3a and C5a was significantly higher in patients with renal involvement compared to patients with nonrenal disease and controls (p < 0.05 and p < 0.01, respectively). The serum levels of C3a were significantly decreased (p < 0.01) in the renal subgroup, while there were no changes in serum levels of C5a comparing the renal and nonrenal groups. There was significant correlation between the disease activity measured by BVAS and the levels of C3a and C5a expressed on MPO+MP.Conclusion.Determination of C3a and C5a on MPO+MP might be considered as a novel biomarker of renal involvement in patients with AAV and may be of importance in the pathogenetic process.

scholarly journals Serum Levels of T Cell Immunoglobulin and Mucin-Domain Containing Molecule 3 in Patients with Systemic Lupus Erythematosus

2020 ◽  
Vol 9 (11) ◽  
pp. 3563
Author(s):  
Tomoyuki Asano ◽  
Naoki Matsuoka ◽  
Yuya Fujita ◽  
Haruki Matsumoto ◽  
Jumpei Temmoku ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cell ◽  
Renal Disease ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Serum Levels ◽  
Organ Damage ◽  
Enzyme Linked Immunosorbent Assay ◽  
Clinical Parameters ◽  
Systemic Lupus

Objective: T cell immunoglobulin and mucin-domain-containing molecule 3 (TIM-3) is implicated in the development of various autoimmune diseases. We aimed to investigate the levels of soluble TIM-3 (sTIM-3) and their associations between clinical parameters in patients with systemic lupus erythematosus (SLE). Methods: Serum samples were collected from 65 patients with SLE and 35 age-matched healthy controls (HCs). The SLE Disease Activity Index 2000 (SLEDAI-2K) and the Systemic Lupus International Collaborating Clinics (SLICC) damage index (SDI) were used to assess SLE disease activity and SLE-related organ damage. British Isles Lupus Assessment Group (BILAG)-2004 index was also used to assess SLE disease activity. Soluble TIM-3 (sTIM-3) in sera from patients with SLE and HCs were evaluated by enzyme-linked immunosorbent assay (ELISA). The results were compared with the clinical parameters of SLE including SLE disease activity. Results: Serum sTIM-3 levels in patients with SLE (median 2123 pg/mL (interquartile range (IQR), 229–7235)) were significantly higher than those in HCs (1363 pg/mL; IQR, 1097–1673; p = 0.0015). Serum levels of sTIM-3 were correlated with disease activity of SLE using the SLEDAI-2K score (p < 0.001, r = 0.53). The serum sTIM-3 levels in SLE patients with active renal disease (BILAG renal index A-B) were significantly higher than those without the active renal disease (BILAG renal index C–E). However, no significant difference was observed in serum sTIM-3 levels between SLE patients with and without active involvement in other organs (BILAG index). Serum sTIM-3 levels were significantly elevated in SLE patients with organ damage (2710 pg/mL; IQR, 256–7235) compared to those without organ damage (1532 pg/mL; IQR, 228–5274), as assessed by the SDI (p = 0.0102). Conclusions: Circulating sTIM-3 levels are elevated in SLE patients, and serum sTIM-3 levels are associated with SLE disease activity and SLE-related organ damage. The data indicate a possible link between the TIM-3/Gal-9 pathway and SLE clinical phenotypes, and further investigation of the TIM-3 pathway in SLE pathophysiology is warranted.

Linking Neutrophil Extracellular Traps and Platelet Activation: A Composite Biomarker Score for Predicting Outcomes after Acute Myocardial Infarction

2021 ◽  
Author(s):  
Kathryn E. Hally ◽  
Olivia M. Parker ◽  
Morgane M. Brunton-O'Sullivan ◽  
Scott A. Harding ◽  
Peter D. Larsen
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Risk Prediction ◽  
Platelet Activation ◽  
Serum Levels ◽  
Neutrophil Extracellular Traps ◽  
Major Adverse Cardiovascular Events ◽  
Enzyme Linked Immunosorbent Assay ◽  
Extracellular Traps ◽  
Soluble P

Abstract Background Activation of both platelets and neutrophils can contribute to the risk of major adverse cardiovascular events (MACE) following acute myocardial infarction (AMI). Neutrophil extracellular traps (NETs) are an important product of the platelet–neutrophil axis and exaggerate vascular damage in cardiovascular disease. Additionally, activated platelets can drive NETosis and are directly linked to thromboembolic risk. Investigating the combined effect of biomarkers for NETosis and platelet activation represents a novel approach to risk prediction post-AMI. Here, we examined the utility of a composite biomarker score, inclusive of both pathways, for predicting MACE post-AMI. Methods and Results In a case–control design, 100 case patients who experienced MACE within 1 year of index admission were matched in a 1:2 ratio with control patients. Serum levels of myeloperoxidase–DNA, neutrophil elastase–DNA, and citrullinated histone H3 were assayed by enzyme-linked immunosorbent assay (ELISA) as markers of NET burden. To measure platelet activation, soluble P-selectin was assayed by ELISA in parallel. Platelet and neutrophil counts were also recorded. Composite biomarker scores, inclusive of biomarkers for NETosis and platelet activation, were assessed using multivariate regression modeling. These composite biomarker scores were independent predictors of 1-year MACE. The strongest association with MACE was observed using a composite of platelet count, soluble P-selectin, and all NET markers (odds ratio: 1.94; 1.16–3.25). Conclusion Here, we demonstrate the importance of combining biomarkers of NETosis and platelet activation for risk prediction in patients with AMI. Combining biomarkers from closely linked, but distinct, biological pathways was more effective than utilizing either type of biomarker alone.

scholarly journals Serum IgA Antibodies Specific to M. leprae Antigens as Biomarkers for Leprosy Detection and Household Contact Tracking

2021 ◽  
Vol 8 ◽  
Author(s):  
Kyssia Karen de Paiva e Silva ◽  
Erick Esteves de Oliveira ◽  
Carolina Martins Moreira Elias ◽  
Ingrid Estevam Pereira ◽  
Roberta Olmo Pinheiro ◽  
...  
Keyword(s):  
Delayed Diagnosis ◽  
Serum Levels ◽  
Household Contact ◽  
Enzyme Linked Immunosorbent Assay ◽  
Roc Curve Analysis ◽  
Additional Tool ◽  
Household Contacts ◽  
Serum Iga ◽  
Contact Tracking ◽  
Diagnosis And Classification

Leprosy remains endemic in several developing countries, such as India and Brazil, in part due to delayed diagnosis that facilitates ongoing transmission. Although immunoglobulins against several Mycobacterium leprae antigens have been indicated for the early diagnosis, and IgA participates in the early stages of leprosy and in subclinical infection, relatively little research has examined anti-M. leprae IgA responses. Here, we investigated serum IgA reactivity against NDO-HSA, LID-1 and NDO-LID, in paucibacillary (PB) and multibacillary (MB) patients and their household contacts, using enzyme-linked immunosorbent assay (ELISA). Diagnostic accuracy of each ELISA was evaluated by receiver operating characteristic (ROC) curve analysis. Our data reveal elevated IgA serum levels against the three M. leprae specific antigens in MB patients, whereas IgA reactivity in PB patients was increased only to NDO-HSA. Further, MB and PB household contacts displayed higher IgA reactivity to NDO-HSA than non-endemic controls. Our data suggest measurement of serum IgA against NDO-HSA as an additional tool in the diagnosis and classification of the disease, with potential utility for household contact follow-up.

The Relationship of Serum Hemojuvelin and Hepcidin Levels with Iron Overload in Nonalcoholic Fatty Liver Disease

2015 ◽  
Vol 24 (3) ◽  
pp. 293-300 ◽  
Author(s):  
Salih Boga ◽  
Huseyin Alkim ◽  
Canan Alkim ◽  
Ali Riza Koksal ◽  
Mehmet Bayram ◽  
...  
Keyword(s):  
Liver Disease ◽  
Iron Overload ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Clinical Characteristics ◽  
Serum Levels ◽  
Fibrosis Stage ◽  
Enzyme Linked Immunosorbent Assay ◽  
Nonalcoholic Fatty Liver

Background & Aims: Mild iron overload is frequently reported in patients with nonalcoholic fatty liver disease (NAFLD). Hepcidin is the master iron-regulatory peptide and hemojuvelin (HJV) is the key regulator of iron-dependent secretion of hepcidin. The aims of this study were to evaluate serum HJV and hepcidin levels in patients with biopsy-proven NAFLD with and without hepatic iron overload, and to identify potential associations of HJV and hepcidin with the clinical characteristics of the patients enrolled. Methods: Serum levels of HJV and hepcidin were measured in 66 NAFLD patients with (n=12) and without (n=54) iron overload, and controls (n=35) by enzyme-linked immunosorbent assay. Hemojuvelin and hepcidin levels were assessed in relation to clinical characteristics and liver histologic evaluation of the participants. Results: Significantly lower serum HJV (281.1 [239.2-353.6] vs. 584.8 [440.3-661] ng/ml, p<0.001) and similar serum hepcidin levels (60.5±31.1 vs. 55.8±11.9 ng/ml, p=0.285) were found in NAFLD patients when compared to controls. İron-overloaded NAFLD patients had significantly lower HJV (249.9 [187.6-296.3] vs. 292.9 [243-435] ng/ml, p=0.032) and significantly higher hepcidin (78.4±35.5 vs. 56.5±28.9ng/ml, p=0.027) levels than NAFLD patients without iron overload. Fibrosis stage was significantly higher in iron overloaded NAFLD group (p<0.001). Ferritin levels correlated significantly both with HOMA-IR (r=0.368, p=0.002) and fibrosis stage (r=0.571, p<0.001). Conclusions: Our findings suggest that HJV levels are low in NAFLD and even lower in iron overloaded NAFLD, while hepcidin levels are higher in NAFLD with iron overload. The gradually decreased HJV and increased hepcidin concentrations in our patients most likely reflect the physiological response to iron accumulation in the liver.

Low Serum Levels of Fibroblast Growth Factor 2 in Gunn Rats: A Hyperbilirubinemia Animal Model of Schizophrenic Symptoms

2020 ◽  
Vol 19 (7) ◽  
pp. 503-508
Author(s):  
Maiko Hayashida ◽  
Sadayuki Hashioka ◽  
Kenji Hayashida ◽  
Shoko Miura ◽  
Keiko Tsuchie ◽  
...  
Keyword(s):  
Animal Model ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Wistar Rats ◽  
Serum Levels ◽  
Significant Negative Correlation ◽  
Enzyme Linked Immunosorbent Assay ◽  
Normal Strain ◽  
Fibroblast Growth ◽  
Gunn Rats

Background: Fibroblast growth factor (FGF) 2 (also referred to as basic FGF) is a multifunctional growth factor that plays a pivotal role in the pro-survival, pro-migration and pro-differentiation of neurons. Method: Because alterations in FGF2 levels are suggested to contribute to the pathogenesis schizophrenia, we investigated serum levels of FGF2 in the Gunn rat, a hyperbilirubinemia animal model of schizophrenic symptoms. Results: The enzyme-linked immunosorbent assay showed that the serum levels of FGF2 in Gunn rats were 5.09 ± 0.236 pg/mL, while those in the normal strain Wistar rats were 11.90 ± 2.142 pg/mL. The serum FGF2 levels in Gunn rats were significantly lower than those in Wistar rats. We also measured serum levels of unconjugated bilirubin (UCB) and found a significant negative correlation between UCB and FGF2 at serum levels in all the rats studied. Conclusion: Since it is known that FGF2 regulates dopaminergic neurons and have anti-neuroinflammatory effects, our finding suggests that low FGF2 levels may contribute to the pathogenesis of schizophrenia, in which disbalanced dopamin-ergic signaling and neuroinflammation are supposed to play certain roles.

Sign in / Sign up

Export Citation Format

Share Document