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

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.

Download Full-text

Isotypes of Epstein-Barr Virus Antibodies in Rheumatoid Arthritis: Association with Rheumatoid Factors and Citrulline-Dependent Antibodies

BioMed Research International ◽

10.1155/2015/472174 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 9

Author(s):

Marie Wulff Westergaard ◽

Anette Holck Draborg ◽

Lone Troelsen ◽

Søren Jacobsen ◽

Gunnar Houen

Keyword(s):

Rheumatoid Arthritis ◽

Lupus Erythematosus ◽

Epstein Barr Virus ◽

Nuclear Antigen ◽

Rheumatoid Factors ◽

Humoral Immune ◽

Barr Virus ◽

Ebv Infection ◽

Epstein Barr ◽

Citrullinated Protein

In order to study the humoral immune response against Epstein-Barr virus (EBV) in patients with rheumatoid arthritis (RA) and to compare it with the two major autoantibody types in RA, plasma samples from 77 RA patients, 28 patients with systemic lupus erythematosus (SLE), and 28 healthy controls (HCs) were investigated by enzyme-linked immunosorbent assays (ELISA). Increased percentages of positives and concentrations of IgG/IgA/IgM antibodies against the latent EBV nuclear antigen-1 (EBNA-1) were observed in RA patients compared to SLE patients and HCs. Increased concentrations and percentages of positives of IgG/IgA/IgM against the early lytic EBV antigen diffuse (EAD) were also found in RA patients compared to HCs but were highest in SLE patients. Furthermore, associations between the elevated EBNA-1 IgA and EBNA-1 IgM levels and the presence of IgM and IgA rheumatoid factors (RFs) and anti-citrullinated protein antibodies (ACPAs, IgG) and between elevated IgA concentrations against EAD and the presence of RFs and ACPAs in RA patients were found. Thus, RA patients had elevated antibodies of all isotypes characteristic of latent EBV infection (whereas SLE patients had elevated antibodies characteristic of lytic EBV infection). Notably, for IgM and IgA (but not IgG), these were associated with the presence of characteristic RA autoantibodies.

Download Full-text

Comparative Study for the Presence of Enterococcal Virulence Factors Gelatinase, Hemolysin and Biofilm Among Clinical and Commensal Isolates of Enterococcus Faecalis

Journal of Laboratory Physicians ◽

10.4103/0974-2727.72159 ◽

2010 ◽

Vol 2 (02) ◽

pp. 100-104 ◽

Cited By ~ 18

Author(s):

Giridhara Upadhyaya P M. ◽

Umapathy B L. ◽

Ravikumar K L.

Keyword(s):

Rheumatoid Arthritis ◽

Enterococcus Faecalis ◽

Virulence Factors ◽

Lupus Erythematosus ◽

Nosocomial Infections ◽

Clinical Isolates ◽

Nuclear Antigen ◽

Biofilm Production ◽

Significant Difference ◽

Citrullinated Peptide

ABSTRACT Background: Biofilm production, gelatinase and hemolysin are the potential virulence factors of Enterococci. Gelatinase and hemolysin producing strains of Enterococcus faecalis have been shown to cause severe infections in animal models. Biofilm production has been shown to enhance the persistence of E. faecalis in urinary bladder and other medical indwelling devices infections. Aims: To compare the presence of gelatinase, hemolysin and biofilm formation among clinical and commensal isolates and to study the co-relation between virulence factors with respect to different clinical specimens. Settings and Design: During the study period of 2 years from July 2004 to July 2006, 200 clinical isolates from nosocomial infections and 100 commensal isolates of E. faecalis were taken for the study. Materials and Methods: The clinical and commensal isolates were tested for the presence of gelatinase, hemolysin and biofilm and compared. The presence of these virulence factors among different clinical isolates was also studied. 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. Statistical Analysis: Chi-square and likelihood ratio analysis were carried out using SSPS version 5.1 software. Results: Results: The clinical isolates produced 39, 16.5 and 32.5% of gelatinase, hemolysin and biofilm, respectively, as compared to 31, 19 and 16% produced by the commensal isolates, respectively. Endotracheal tube infection, urinary tract infection, umbilical catheter tip infected isolates produced 60.8, 86.6 and 100% biofilm, respectively. Conclusion: Significant difference in the production of biofilm (P<0.001) was noted between clinical and commensal isolates. Organism isolated from medically indwelling devices produced high amount of biofilm, confirming its role in colonization and causing nosocomial infections.

Download Full-text

EBNA1 IgM-Based Discrimination Between Rheumatoid Arthritis Patients, Systemic Lupus Erythematosus Patients and Healthy Controls

Antibodies ◽

10.3390/antib8020035 ◽

2019 ◽

Vol 8 (2) ◽

pp. 35 ◽

Cited By ~ 1

Author(s):

Nicole Hartwig Trier ◽

Anette Holck Draborg ◽

Louise Sternbæk ◽

Lone Troelsen ◽

Janni Lisander Larsen ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Epstein Barr Virus ◽

Connective Tissue Diseases ◽

Nuclear Antigen ◽

Healthy Controls ◽

Systemic Lupus ◽

Barr Virus ◽

Epstein Barr

Epstein–Barr Virus (EBV) has been associated with development of rheumatic connective tissue diseases like rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in genetically susceptible individuals. Diagnosis of RA and SLE relies on clinical criteria in combination with the presence of characteristic autoantibodies. In addition, antibodies to several EBV antigens have been shown to be elevated in patients with these diseases compared to healthy controls (HC). Here, we elaborated improved enzyme-linked immunosorbent assays for antibodies (IgM, IgA, IgG) to the EBV proteins Epstein-Barr Virus nuclear antigen (EBNA)1 and early antigen diffuse (EAD) in order to determine their potential diagnostic role. We showed that especially EBNA1 IgM distinguished RA from SLE and HCs and also distinguished SLE from HCs. EBNA1 IgA was almost as effective in differentiating RA from SLE and HC, while EAD IgG and IgA were able to discern SLE patients from RA patients and HCs. Collectively, these findings illustrate the potential diagnostic use of antibodies to EBV proteins to diagnose RA and to differentiate SLE from RA.

Download Full-text

Association analysis of anti-Epstein-Barr nuclear antigen-1 antibodies, anti-cyclic citrullinated peptide antibodies, the shared epitope and smoking status in Brazilian patients with rheumatoid arthritis

Clinics ◽

10.1590/s1807-59322011000800016 ◽

2011 ◽

Vol 66 (8) ◽

pp. 1401-1406 ◽

Cited By ~ 8

Author(s):

Michel Alexandre Yazbek ◽

Silvia de Barros-Mazon ◽

Cláudio Lúcio Rossi ◽

Ana Carolina Londe ◽

Lilian Tereza Lavras Costallat ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Association Analysis ◽

Shared Epitope ◽

Smoking Status ◽

Nuclear Antigen ◽

Cyclic Citrullinated Peptide ◽

Epstein Barr ◽

Citrullinated Peptide ◽

Epstein Barr Nuclear Antigen ◽

Peptide Antibodies

Download Full-text

Antifibrillarin autoantibodies present in systemic sclerosis and other connective tissue diseases interact with similar epitopes.

Journal of Experimental Medicine ◽

10.1084/jem.181.3.1027 ◽

1995 ◽

Vol 181 (3) ◽

pp. 1027-1036 ◽

Cited By ~ 32

Author(s):

K N Kasturi ◽

A Hatakeyama ◽

H Spiera ◽

C A Bona

Keyword(s):

Systemic Sclerosis ◽

Connective Tissue ◽

Lupus Erythematosus ◽

Competitive Inhibition ◽

Molecular Mimicry ◽

Connective Tissue Diseases ◽

Nuclear Antigen ◽

Barr Virus ◽

Recombinant Fusion Proteins ◽

Epstein Barr

Autoantibodies specific against fibrillarin, a 34-kD nucleolar protein associated with U3-snRNP, are present in patients with systemic sclerosis (SSc). To understand the mechanisms involved in the induction of these autoantibodies, we prepared a series of human fibrillarin recombinant proteins covering the entire molecule and analyzed their interaction with the autoantibodies present in various connective tissue diseases. Our results showed that antifibrillarin autoantibodies are present not only in SSc, as previously reported, but also in a variety of other connective tissue diseases. Patients with SSc (58%), mixed connective tissue diseases (60%), CREST syndrome (calcinosis, Raynaud phenomenon, esophageal dismotility, sclerodactyly, and telangiectasia syndrome) (58%), systemic lupus erythematosus (39%), rheumatoid arthritis (60%), and Sjogern's syndrome (84%) showed presence of antifibrillarin autoantibodies. Results obtained from competitive inhibition radioimmunoassay and Western blot analyses with purified recombinant fusion proteins revealed that these autoantibodies react primarily with epitope(s) present in the NH2- (AA 1-80) and COOH-terminal (AA 276-321) domains of fibrillarin. Autoantibodies reacting with internal regions of fibrillarin are less frequent. Analysis of the hydrophilicity profiles of reactive peptides showed presence of three potential antigenic sites in the NH2- and two in the COOH-terminal regions. While a hexapeptide sequence NH2 terminus of fibrillarin is shared with an Epstein-Barr virus-encoded nuclear antigen, the COOH-terminal region shares sequence homology with P40, the capsid protein encoded by herpes virus type 1. Interestingly, these two regions of fibrillarin also contain the most immunodominant sequences, as predicted by surface probability and the Jameson and Wolf antigenic index. These observations suggest that molecular mimicry might play an important role in the induction of antifibrillarin autoantibodies.

Download Full-text