scholarly journals High Concentrations of Angiopoietin-Like Protein 4 Detected in Serum from Patients with Rheumatoid Arthritis Can Be Explained by Non-Specific Antibody Reactivity

PLoS ONE ◽  
2017 ◽  
Vol 12 (1) ◽  
pp. e0168922
Author(s):  
Elena Makoveichuk ◽  
Toralph Ruge ◽  
Solveig Nilsson ◽  
Anna Södergren ◽  
Gunilla Olivecrona
Keyword(s):  
Rheumatoid Arthritis ◽  
Specific Antibody ◽  
Antibody Reactivity ◽  
High Concentrations

scholarly journals Impaired Gamma Interferon Responses against Parvovirus B19 by Recently Infected Children

2000 ◽  
Vol 74 (21) ◽  
pp. 9903-9910 ◽  
Author(s):  
Amanda Corcoran ◽  
Sean Doyle ◽  
David Waldron ◽  
Alfred Nicholson ◽  
Bernard P. Mahon
Keyword(s):  
Rheumatoid Arthritis ◽  
Immune Responses ◽  
Specific Antibody ◽  
Parvovirus B19 ◽  
Gamma Interferon ◽  
Capsid Proteins ◽  
Exact Nature ◽  
Unique Region ◽  
Antibody Reactivity ◽  
Ifn Γ

ABSTRACT Parvovirus B19 is the causative agent of “fifth disease” of childhood. It has been implicated in a variety of conditions, including unsuccessful pregnancy and rheumatoid arthritis, and is a potential contaminant of blood products. There has been little study of immunity to parvovirus B19, and the exact nature of the protective humoral and cell-mediated immune response is unclear. Immune responses to purified virus capsid proteins, VP1 and VP2, were examined from a cohort of recently infected children and compared with responses from long-term convalescent volunteers. The results demonstrate that antibody reactivity is primarily maintained against conformational epitopes in VP1 and VP2. The unique region of VP1 appears to be a major target for cell-mediated immune responses, particularly in recently infected individuals. We confirm that antibody reactivity against linear epitopes of VP2 is lost shortly after infection but find no evidence of the proposed phenotypic switch in either the subclass of parvovirus B19-specific antibody or the pattern of cytokine production by antigen-specific T cells. The dominant subclass of specific antibody detected from both children and adults was immunoglobulin G1. No evidence was found for interleukin 4 (IL-4) or IL-5 production by isolated lymphocytes from children or adults. In contrast, lymphocytes from convalescent adults produced a typical type 1 response associated with high levels of IL-2 and gamma interferon (IFN-γ). However, we observed a significant (P < 0.001) deficit in the production of IFN-γ in response to VP1 or VP2 from lymphocytes isolated from children. Taken together, these results imply that future parvovirus B19 vaccines designed for children will require the use of conformationally preserved capsid proteins incorporating Th1 driving adjuvants. Furthermore, these data suggest novel mechanisms whereby parvovirus B19 infection may contribute to rheumatoid arthritis and unsuccessful pregnancy.

scholarly journals FRI0596 NOVEL AUTOANTIBODY BIOMARKERS FOR THE PREDICTION OF THERAPY RESPONSE IN RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 904.1-904
Author(s):  
P. Vandormael ◽  
A. Pues ◽  
E. Sleurs ◽  
P. Verschueren ◽  
V. Somers
Keyword(s):  
Rheumatoid Arthritis ◽  
Therapy Response ◽  
Autoimmune Disorder ◽  
First Line ◽  
Research Support ◽  
Serum Samples ◽  
Glucocorticoid Treatment ◽  
Baseline Serum ◽  
Disease Remission ◽  
Antibody Reactivity

Background:Rheumatoid arthritis (RA) is an autoimmune disorder that is characterized by chronic inflammation of the joint synovium and presence of autoantibodies in most patients. For RA, many treatments are currently available but each treatment will only induce disease remission in a subset of patients. Moreover, finding out which patients respond well to first-line therapy with classical synthetic disease modifying anti-rheumatic drugs (csDMARDs), still largely depends on trial and error.Objectives:In this study, we aim to find novel RA autoantibody biomarkers that predict therapy response to csDMARDs before the initiation of treatment.Methods:In the CareRA trial, a Flemish multicenter study of different treatment regimes, serum samples were collected from RA patients that did or did not show disease remission (DAS28(CRP)<2.6) in response to csDMARDs, combined with a step down glucocorticoid treatment. In our study, baseline samples, collected before the start of treatment, were used to determine predictive antibody reactivity. A cDNA phage display library, representing the antigens from RA synovial tissue, was constructed and screened for antibody reactivity in baseline serum samples of RA patients that failed to reach remission at week 16. Using enzyme-linked immunosorbent assays (ELISA), antibody reactivity against the identified antigens was initially determined in pooled baseline serum samples of RA patients that did (n=50) or did not (n=40) reach disease remission at week 16. Antigenic targets that showed increased antibody reactivity in pools from patients that did not reach disease remission, were further validated in individual serum samples of 69 RA patients that did not reach DAS28(CRP) remission at week 16, and 122 RA patients that did.Results:Screening and validation of antibody reactivity resulted in 41 novel antigens. The retrieved antigenic sequences correspond to (parts of) known proteins and to randomly formed peptides. A panel of 3 of these peptide antigens could be composed, whose baseline antibody reactivity correlated with lack of therapy response at week 16. Presence of antibodies against at least one of these 3 antigens was significantly higher in individual samples of RA patients that did not reach DAS28(CRP) remission (43 vs. 29%, p=0.041), or that failed to reach ACR 70 (42 vs. 26%, p=0.029) response criteria at week 16, compared to RA patients that did reach these respective criteria. In addition, RA patients which were positive for this antibody panel at baseline, also showed less DAS(CRP) remission at week 4 and week 8.Conclusion:We have identified a set of 3 antibody biomarkers that can predict failure of early disease remission after first-line RA therapy, which might contribute to personalized medicine decisions.Disclosure of Interests:Patrick Vandormael: None declared, Astrid Pues: None declared, Ellen Sleurs: None declared, Patrick Verschueren Grant/research support from: Pfizer unrestricted chair of early RA research, Speakers bureau: various companies, Veerle Somers Grant/research support from: Research grant from Pfizer and BMS

Are neutrophil extracellular traps the link for the cross-talk between periodontitis and rheumatoid arthritis physiopathology?

Rheumatology ◽  
2021 ◽  
Author(s):  
Sicília Rezende Oliveira ◽  
José Alcides A de Arruda ◽  
Ayda Henriques Schneider ◽  
Valessa Florindo Carvalho ◽  
Caio Machado ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cross Talk ◽  
Neutrophil Extracellular Traps ◽  
Periodontal Therapy ◽  
Clinical Parameters ◽  
Extracellular Traps ◽  
Early Ra ◽  
The Cross ◽  
High Concentrations ◽  
The Impact

Abstract Objectives Neutrophil extracellular traps (NETs) play a role in the pathogenesis of periodontitis and rheumatoid arthritis (RA). However, it remains poorly understood whether NETs participate in the cross-talk between periodontitis and RA. Herein, we investigated the production of NETs in individuals with periodontitis and RA and its association with clinical parameters. The impact of periodontal therapy on RA and NET release was also assessed. Methods The concentration of NETs and cytokines was determined in the saliva and plasma of individuals with early RA (n = 24), established RA (n = 64), and individuals without RA (n = 76). The influence of periodontitis on the production of NETs and cytokines was also evaluated. Results Individuals with early RA had a higher concentration of NETs in saliva and plasma than individuals with established RA or without RA. Periodontitis resulted in an increase in the concentration of NETs of groups of individuals without RA and with early RA. The proportion of individuals with high concentrations of IL-6, IL-10 and GM-CSF was higher among individuals with periodontitis than among individuals without periodontitis. The concentrations of TNF-α, IL-6, IL-17/IL-25, and IL-28A were particularly high in individuals with early RA. Worse periodontal clinical parameters, RA onset and RA activity were significantly associated with circulating NETs. Periodontal therapy was associated with a reduction in the concentration of NETs and inflammatory cytokines and amelioration in periodontitis and RA. Conclusion This study reveals that NETs are a possible link between periodontitis and RA, with periodontal therapy resulting in a dramatic switch in circulating NET levels.

FRI0068 LIPID PROFILE AND BONE MINERAL DENSITY IN PATIENTS WITH RHEUMATOID ARTHRITIS: IS THERE AN ADDED RISK OF OSTEOPOROSIS?

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 610.1-611
Author(s):  
B. Touil ◽  
H. Azzouzi ◽  
O. Lamkhanat ◽  
F. Chennouf ◽  
I. Linda
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Mineral Density ◽  
Lumbar Spine ◽  
Linear Regression ◽  
Femoral Neck ◽  
Lipid Profile ◽  
Density Lipoprotein ◽  
Mineral Density ◽  
High Tc ◽  
High Concentrations

Background:Bone is a target in many inflammatory rheumatic diseases such as rheumatoid arthritis (RA). It has been supposed that an atherogenic lipid profile could be associated with lower bone mineral density (BMD) and vertebral fractures (VF).Objectives:We aimed to evaluate the relationship between the lipid profile, BMD and the presence of VF in RA patients.Methods:A cross sectional study was conducted in a population of 169 established RA. In each subject we evaluated the body mass index (BMI), tobacco use, alcohol consumption, presence of diabetes and high blood pression, lipid profile (total cholesterol (TC), High density lipoprotein cholesterol (HDLc), low density lipoprotein cholesterol (LDLc), triglycerides (TG), and VF. RA characteristics were also assessed (disease duration, disease activity score (DAS), auto antibodies, corticosteroid intake, and secondary sjogren’s syndrome). BMD was measured by dual energy X-ray absorptiometry (DXA) in lumbar spine and femoral neck. Logistic and linear regression were performed with SPSS 20, both BMD and VF were assessed as dependent variables.Results:The mean age was 55.5±11.9 years, with a female predominance (152 women). The average BMI was 26.79 ± 5.36. We had 24.3 % of hypertensive patients and 16.6 % of diabetics. The average lipid concentrations were 4.39±1 mmol/L for TC, 1.293±0.36 mmol/L for HDLc, 2.74±0.80 mmol/L for LDLc and 1.25±0.62 mmol/L for TG. At the linear regression there was no correlation between plasma lipid concentrations and BMD, whether at the lumbar spine or the femoral neck. However we found a significant correlation between VF and high TC concentrations (p=0.043, OR: 2.864, 95% IC [1.036-7.922]). At the multivariate regression, high TC levels were still associated with VF, adjusted in BMI, age and the duration of corticosteroid use (p=0.006, OR: 6.07, 95% CI[1.69- 21.77]). The same finding was observed between high concentrations of HDLc and the prevalence of VF adjusted in the same variables (p=0.006, OR: 197.01, 95% CI [4.64-8363.51]).Conclusion:Although there was no relation between lipid plasma levels and BMD in our population. There was a significant association between high concentrations of TC, HDLc and the prevalence of VF.Disclosure of Interests:None declared

Loss of Gag-Specific Antibody Reactivity in Cattle Experimentally Infected with Bovine Immunodeficiency-Like Virus

1995 ◽  
Vol 8 (1) ◽  
pp. 27-36 ◽  
Author(s):  
JEFFREY A. ISAACSON ◽  
JAMES A. ROTH ◽  
CHARLES WOOD ◽  
SUSAN CARPENTER
Keyword(s):  
Specific Antibody ◽  
Antibody Reactivity

Artefactual 25-OH vitamin D concentration in multiple myeloma

2017 ◽  
Vol 54 (6) ◽  
pp. 716-720 ◽  
Author(s):  
Michal WS Ong ◽  
Rashim Salota ◽  
Tracy Reeman ◽  
Marta Lapsley ◽  
Lydia Jones
Keyword(s):  
Rheumatoid Arthritis ◽  
Vitamin D ◽  
Rheumatoid Factor ◽  
Reference Method ◽  
Sun Exposure ◽  
High Concentration ◽  
History Of ◽  
High Concentrations ◽  
Vitamin D Supplements ◽  
25 Oh Vitamin D

The most commonly used techniques to measure vitamin D are automated immunoassays which are known to be affected by interferences, especially from immunoglobulins present in the patient’s serum. We present a case of a patient with myeloma in whom interference with the vitamin D assay was identified. An 83-year-old female, known to have IgG myeloma, was found to have a high concentration of 25-OH vitamin D on a routine test without any signs of vitamin D toxicity. She was not taking vitamin D supplements or any other multivitamin preparation and had minimal sun exposure. The initial and subsequent samples run by the ARCHITECT 25-OH vitamin D assay (chemiluminescent microparticle immunoassay technology, Abbott Laboratories, Abbott Park, IL) showed a high concentration of 25-OH vitamin D of 281 nmol/L and 327 nmol/L, respectively. Further fresh samples taken for 25-OH vitamin D and analysed by liquid chromatography-mass spectrometry (LC-MS/MS) and ARCHITECT analysis showed results of 49 nmol/L and 289 nmol/L, respectively. Our patient had high concentrations of circulating IgG paraproteins and had a long history of rheumatoid arthritis; paraproteins and rheumatoid factor may interfere in the assay. In conclusion, we report a case of a patient with IgG myeloma and rheumatoid arthritis with high concentrations of 25-OH vitamin D detected by the Abbott ARCHITECT, but not by a reference method (LC-MS/MS). The most likely cause of the discordant results is interference in the immunoassay by the paraprotein but interference from rheumatoid factor remains a possibility.

scholarly journals HPLC Determination of Erythrocyte Methotrexate Polyglutamates after Low-Dose Methotrexate Therapy in Patients with Rheumatoid Arthritis

2003 ◽  
Vol 49 (10) ◽  
pp. 1632-1641 ◽  
Author(s):  
Thierry Dervieux ◽  
Diana Orentas Lein ◽  
John Marcelletti ◽  
Ken Pischel ◽  
Katie Smith ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Low Dose ◽  
Direct Injection ◽  
Reversed Phase ◽  
Hplc Method ◽  
Stability Study ◽  
Limit Of Quantification ◽  
Methotrexate Polyglutamates ◽  
Routine Monitoring ◽  
High Concentrations

Abstract Background: Methotrexate (MTX) may produce antiarthritic effects through polyglutamation to methotrexate polyglutamates (MTXPGs), a process that covalently attaches sequential γ-linked glutamic residues to MTX. We sought to develop an innovative HPLC method for the quantification of these metabolites in erythrocytes. Methods: Two alternative approaches were developed. In the first approach, MTXPGs from 50 μL of packed erythrocytes were converted to MTX in the presence of plasma γ-glutamyl hydrolase and mercaptoethanol at 37 °C. In the second approach, MTXPG species (up to the hepta order of glutamation) from 100 μL packed erythrocytes were directly quantified in a single run. In both methods, the MTXPGs were extracted from the biological matrix by a simple perchloric acid deproteinization step with direct injection of the extract into the HPLC. The chromatography used a C18 reversed-phase column, an ammonium acetate/acetonitrile buffer, and postcolumn photo-oxidation of MTXPGs to fluorescent analytes. Results: Intra- and interday imprecision (CVs) were &lt;10% at low and high concentrations of analytes for both methods. The limit of quantification was 5 nmol/L. In 70 patients with rheumatoid arthritis receiving weekly low-dose MTX, the mean (SD) total MTXPG concentration measured after conversion of MTXPGs to MTX was similar to the total MTXPG concentration calculated from the sum of individual MTXPG species [117 (56) vs 120 (59) nmol/L; r = 0.97; slope = 1.0]. The triglutamate predominated over all other MTXPG species (36% of total), the pentaglutamate was the highest order of glutamation detected, and a stability study revealed no change in the polyglutamation pattern in erythrocytes 48 h after phlebotomy when the specimen was stored at 2–8 °C. Conclusion: The proposed method for quantification of erythrocyte MTXPGs is rapid, sensitive, and accurate and can be applied to the routine monitoring of MTX therapy.

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