scholarly journals Specificity of Anti-Citrullinated Protein Antibodies to Citrullinated α-Enolase Peptides as a Function of Epitope Structure and Composition

Antibodies ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 27
Author(s):  
Ilaria Fanelli ◽  
Paolo Rovero ◽  
Paul Robert Hansen ◽  
Jette Frederiksen ◽  
Gunnar Houen ◽  
...  
Keyword(s):  
Peptide Conformation ◽  
Nuclear Antigen ◽  
Enzyme Linked Immunosorbent Assay ◽  
World Population ◽  
Epstein Barr Virus Infection ◽  
Barr Virus ◽  
Epitope Structure ◽  
Epstein Barr ◽  
Citrullinated Protein ◽  
Citrullinated Peptide

Rheumatoid arthritis (RA) is an autoimmune disease affecting approximately 1–2% of the world population. In addition to the first discovered serologic markers for RA, the rheumatoid factors (RFs), anti-citrullinated protein antibodies (ACPAs) are even more specific for the disease compared to RFs and are found in 70–80% of RA patient sera. RA etiopathogenesis still needs to be elucidated, as different factors are proposed to be involved, such as Epstein–Barr virus infection. Hence, understanding the interaction between ACPAs and their citrullinated peptide targets is relevant for a better knowledge of RA pathophysiology and for diagnostic purposes. In this study, a cohort of RA sera, healthy control sera and multiple sclerosis sera were screened for reactivity to a variety of citrullinated peptides originating from α-enolase, pro-filaggrin, proteoglycan and Epstein–Barr nuclear antigen-2 by enzyme-linked immunosorbent assay. ACPA reactivity to citrullinated α-enolase peptides was found to depend on peptide length and peptide conformation, favouring cyclic (disulfide bond) conformations for long peptides and linear peptides for truncated ones. Additional investigations about the optimal peptide conformation for ACPA detection, employing pro-filaggrin and EBNA-2 peptides, confirmed these findings, indicating a positive effect of cyclization of longer peptides of approximately 20 amino acids. Moreover, screening of the citrullinated peptides confirmed that ACPAs can be divided into two groups based on their reactivity. Approximately 90% of RA sera recognize several peptide targets, being defined as cross-reactive or overlapping reactivities, and whose reactivity to the citrullinated peptide is considered primarily to be backbone-dependent. In contrast, approximately 10% recognize a single target and are defined as nonoverlapping, primarily depending on the specific amino acid side-chains in the epitope for a stable interaction. Collectively, this study contributed to characterize epitope composition and structure for optimal ACPA reactivity and to obtain further knowledge about the cross-reactive nature of ACPAs.

Epstein-Barr virus-specific antibody response in cerebrospinal fluid and serum of patients with multiple sclerosis

2010 ◽  
Vol 16 (7) ◽  
pp. 883-887 ◽  
Author(s):  
Massimiliano Castellazzi ◽  
Carmine Tamborino ◽  
Alice Cani ◽  
Elena Negri ◽  
Eleonora Baldi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Neurological Disorders ◽  
Epstein Barr Virus ◽  
Serum Levels ◽  
Nuclear Antigen ◽  
Enzyme Linked Immunosorbent Assay ◽  
Barr Virus ◽  
Epstein Barr ◽  
Multiple Sclerosis Patients

Cerebrospinal fluid and serum levels and intrathecal synthesis of anti-Epstein—Barr virus (EBV) IgG were measured by enzyme-linked immunosorbent assay in 80 relapsing—remitting multiple sclerosis patients grouped according to clinical and magnetic resonance imaging (MRI) evidence of disease activity. Eighty patients with other inflammatory neurological disorders (OIND) and 80 patients with non-inflammatory neurological disorders (NIND) served as neurological controls. Cerebrospinal fluid concentrations were higher in OIND than in multiple sclerosis ( p < 0.0001) and NIND ( p < 0.01) for anti-viral-capsid-antigen (anti-VCA) IgG, in multiple sclerosis than in NIND ( p < 0.01) and in OIND than in NIND ( p < 0.05) for anti-EBV nuclear antigen-1 (EBNA-1) IgG. Serum levels were more elevated in OIND than in multiple sclerosis ( p < 0.05) and in MRI inactive than in MRI active multiple sclerosis ( p < 0.0001) for anti-VCA IgG, and in multiple sclerosis than in OIND and NIND ( p < 0.01) for anti-EBNA-1 IgG. Serum titres of anti-VCA and anti-EBNA-1 IgG were also positively ( p < 0.05) and inversely ( p < 0.001) correlated, respectively, with the Expanded Disability Status Scale. An intrathecal IgG production of anti-VCA and anti-EBNA-1 IgG, as indicated by Antibody Index, was present only in a limited number of multiple sclerosis patients and controls (range from 1.3 to 6.3%). These findings do not support a direct pathogenetic role of EBV-targeted humoral immune response in multiple sclerosis.

scholarly journals Detection of Viral Citrullinated Peptide Antibodies Directed Against EBV or VCP: In Early Rheumatoid Arthritis Patients of Indian Origin

2010 ◽  
Vol 2 (02) ◽  
pp. 093-099
Author(s):  
Sudha S Deo ◽  
Rashmi R Shetty ◽  
Kejal J Mistry ◽  
Arun R Chogle
Keyword(s):  
Rheumatoid Arthritis ◽  
Early Rheumatoid Arthritis ◽  
Lupus Erythematosus ◽  
Nuclear Antigen ◽  
Barr Virus ◽  
Igm Antibody ◽  
Significant Difference ◽  
Epstein Barr ◽  
Low Sensitivity ◽  
Citrullinated Peptide

ABSTRACT Aim: Study was undertaken to analyze the frequency of anti-viral citrullinated peptide (anti-VCP) antibodies in sera from patients with early rheumatoid arthritis (ERA). Materials and Methods: Viral citrullinated peptide (VCP) and Epstein-Barr nuclear antigen (EBNA-1) peptide were commercially prepared and antibodies to these were determined in 25 patients of ERA, 40 disease control patients constituting 25 rheumatoid arthritis (RA), 7 systemic lupus erythematosus (SLE), 2 scleroderma, 1 spondyloarthritis (SpA), 1 juvenile rheumatoid arthritis (JRA), 1 osteoarthritis (OA), 1 psoriatic arthritis (PsA), 1 undifferentiated arthritis (UA), and 1 gout and 25 healthy controls (HCs) were taken for comparison. In-house ELISA was established for both the antibodies while cyclic citrullinated peptide (CCP) antibody was detected by commercial ELISA kit. Results: Significant increase in VCP antibody by ERA and disease controls than healthy normal was observed. VCP IgM antibody was significantly increased in RA patients than HC. The presence of VCP antibody signifies a good marker for ERA. We observed significant difference in the VCP IgG and IgM antibody when compared to EBNA-1. In-house ELISA established for EBNA-1 and VCP antibodies showed low sensitivity but 96% specificity. Conclusions: We observed that sera from early RA patients reacted to the deiminated protein encoded by Epstain Barr Virus (EBV). Thus a possible role of virus in inducing an anti-citrullinated peptide antibody (ACPA) response reveals viral etiology in this disease.

scholarly journals Early events in Epstein-Barr virus infection provide a model for B cell activation.

1985 ◽  
Vol 162 (1) ◽  
pp. 45-59 ◽  
Author(s):  
D A Thorley-Lawson ◽  
K P Mann
Keyword(s):  
B Cells ◽  
B Cell ◽  
Epstein Barr Virus ◽  
Rna Synthesis ◽  
Cell Activation ◽  
Nuclear Antigen ◽  
Epstein Barr Virus Infection ◽  
B Cell Activation ◽  
Barr Virus ◽  
Epstein Barr

We have used Epstein-Barr virus (EBV) infection in vitro to delineate two distinct stages in B cell activation. Previous studies have shown that the BLAST-2 (EBVCS) (EBV cell surface) activation antigen is expressed on a small fraction of B cells within 24 h of stimulation with a variety of agents, including mitogens and EBV. In this study, we have been able to isolate the BLAST-2 (EBVCS)+ cells early after activation/infection with EBV. These cells are small B cells that are actively synthesizing RNA but not DNA, and are, therefore, clearly distinct from large proliferating lymphoblasts. In addition, they contain multiple copies of the EBV genome, express the viral nuclear antigen (EBNA) and, most importantly, proceed to undergo transformation when placed back in culture. By comparison, the BLAST-2 (EBVCS)- population does not undergo transformation, even though a fraction of these cells are activated for RNA synthesis and express EBNA. Thus, using the EBV system, we have been able to show directly that an activated B cell first expresses the BLAST-2 (EBVCS) antigen concomitant with an increase in RNA synthesis, and then subsequently proceeds to differentiate into a proliferating lymphoblast.

Age at Epstein-Barr virus infection and Epstein-Barr virus nuclear antigen-1 antibodies in Swedish children

2012 ◽  
Vol 1 (3) ◽  
pp. 136-138 ◽  
Author(s):  
K. Claire Simon ◽  
Shanie Saghafian-Hedengren ◽  
Eva Sverremark-Ekström ◽  
Caroline Nilsson ◽  
Alberto Ascherio
Keyword(s):  
Virus Infection ◽  
Epstein Barr Virus ◽  
Nuclear Antigen ◽  
Epstein Barr Virus Infection ◽  
Barr Virus ◽  
Epstein Barr ◽  
Barr Virus Infection

Hypovitaminosis-D and EBV: no interdependence between two MS risk factors in a healthy young UK autumn cohort

2013 ◽  
Vol 20 (6) ◽  
pp. 751-753 ◽  
Author(s):  
Caren Ramien ◽  
Annette Pachnio ◽  
Sofia Sisay ◽  
Jusnara Begum ◽  
Alison Leese ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Sclerosis ◽  
Epstein Barr Virus ◽  
Quantitative Polymerase Chain Reaction ◽  
Hypovitaminosis D ◽  
Nuclear Antigen ◽  
Epstein Barr Virus Infection ◽  
Barr Virus ◽  
Epstein Barr

Late Epstein-Barr virus infection and hypovitaminosis-D as environmental risk factors in the pathogenesis of multiple sclerosis are gaining great interest. We, therefore, tested for in-vivo interdependence between Epstein-Barr-virus (EBV)-status and 25-hydroxyvitamin D3 (25(OH)D3) -level in healthy young individuals from a United Kingdom (UK) autumn cohort. EBV-load was measured by quantitative polymerase chain reaction and 25(OH)D3 levels by isotope-dilution liquid chromatography-tandem mass spectrometry. This young, healthy UK autumn cohort showed surprisingly low levels of 25(OH)D3 (mean value: 40.5 nmol/L ± 5.02). Furthermore, we found that low 25(OH)D3 levels did not impact on EBV load and anti-EBV nuclear antigen-1 (EBNA-1) titers. However, we observed a correlation between EBV load and EBNA-1 titers. These observations should be of value in the study of the potential relationship between hypovitaminosis-D and EBV-status in the pathophysiology of multiple sclerosis.

False Positive EBNA IgM and IgG Antibody Tests for Infectious Mononucleosis in Children

PEDIATRICS ◽  
1994 ◽  
Vol 94 (6) ◽  
pp. 892-894 ◽  
Author(s):  
Dorothy Levine ◽  
Rosemary Klenk ◽  
Alan Morelli ◽  
Nancy Hofreuter ◽  
Richard C. Tilton ◽  
...  
Keyword(s):  
Virus Infection ◽  
Infectious Mononucleosis ◽  
False Positive ◽  
Epstein Barr Virus ◽  
Enzyme Linked Immunosorbent Assay ◽  
Epstein Barr Virus Infection ◽  
Igg Antibody ◽  
Barr Virus ◽  
Epstein Barr ◽  
Barr Virus Infection

Objectives. To assess the reliability of the Monolert test, a new enzyme-linked immunosorbent assay for the diagnosis of acute infectious mononucleosis (IM). Design. A retrospective laboratory and clinical analysis of 38 children diagnosed with acute IM. Setting. A suburban pediatric practice in Connecticut. Patients. Thirty-eight children (ages 18 months to 17 years) who were diagnosed with acute IM using the Monolert test during the period October 1992 to August 1993. Results. Eighty-three percent of these children had no evidence of Epstein-Barr virus infection on subsequent investigation. The false positive results of the Monolert test could not be explained on the basis of elevated antibody titers to either cytomegalovirus or Borrelia burgdorferi. Conclusion. Monolert is a poor screening test and is of little apparent value as a diagnostic test for acute Epstein-Barr virus infection in pediatric patients.

Investigation on the serum antibodies levels against Epstein-Barr virus in pulmonary lymphoepithelioma-like carcinoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18186-18186
Author(s):  
S. Niraula ◽  
Y. S. Zong ◽  
L. Z. Zhai ◽  
C. C. Guo ◽  
T. Y. Lin
Keyword(s):  
Epstein Barr Virus ◽  
High Titer ◽  
Serum Levels ◽  
Small Sample ◽  
Nuclear Antigen ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serum Antibodies ◽  
Barr Virus ◽  
Antigen Complex ◽  
Epstein Barr

18186 Background: Pulmonary lymphoepithelioma-like carcinoma (PLELC) belongs to large cell sub-type of non-small cell lung cancer (NSCLC) with just about 160 cases reported previously. Its epidemiology, prognosis and therapeutic approach is evidently different from other NSCLCs. EBV infection is seen in 100% of Asian PLELC patients whenever tested. The aim of this study was to analyze serum antibodies level against EBV in PLELC patients. Methods: Sera of all seven patients with re-confirmed PLELC from a single institute in Canton, China in the past 4 years were collected. Serum levels of 8 different antibodies against EBV (Epstein-Barr virus): EBNA1 (EBV nuclear antigen 1- IgA and IgG), Zta (Bam Z transactivator antigen-IgA and IgG), VCA-p18 (Viral capsid antigen-p18-IgA and IgG), VCA-antigen complex (VCA-IgA) and Early antigen complex (EA-IgA ) were measured in each of these patients using enzyme-linked immunosorbent assay and Immunoenzymatic assay respectively. Results: Out of 7 cases, 6 showed high EBNA-1 level, 4 showed high zta, 3 showed high VCA-p18, 3 showed high titer of VCA complex and 2 showed high EA complex titer ( Table 1 ) Conclusions: Though small sample size, this is the first study in this depth ever to conclude that sera of all Asian patients with pulmonary LELC have high antibody titers against EBV. The infection mainly is latency II type as seen in Nasopharyngeal carcinoma and Hodgkin’s disease as well. A small portion of PLELC express lytic products such as Zta, EA and VCA. The authors assume that pre-therapeutic measurement of serum levels of anti-EBV antibodies (at least 2 kinds) is highly warranted in suspected Asian NSCLC patients. Positive result strongly puts PLELC into differential diagnosis. [Table: see text] No significant financial relationships to disclose.

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