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

1995 ◽  
Vol 181 (3) ◽  
pp. 1027-1036 ◽  
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.

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

Antibodies ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 35 ◽  
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.

scholarly journals Molecular mimicry between Anoctamin 2 and Epstein-Barr virus nuclear antigen 1 associates with multiple sclerosis risk

2019 ◽  
Vol 116 (34) ◽  
pp. 16955-16960 ◽  
Author(s):  
Katarina Tengvall ◽  
Jesse Huang ◽  
Cecilia Hellström ◽  
Patrick Kammer ◽  
Martin Biström ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Sclerosis ◽  
T Cell ◽  
Epstein Barr Virus ◽  
Molecular Mimicry ◽  
Nuclear Antigen ◽  
Immune Reactivity ◽  
Barr Virus ◽  
Epstein Barr ◽  
Antibody Levels

Multiple sclerosis (MS) is a chronic inflammatory, likely autoimmune disease of the central nervous system with a combination of genetic and environmental risk factors, among which Epstein-Barr virus (EBV) infection is a strong suspect. We have previously identified increased autoantibody levels toward the chloride-channel protein Anoctamin 2 (ANO2) in MS. Here, IgG antibody reactivity toward ANO2 and EBV nuclear antigen 1 (EBNA1) was measured using bead-based multiplex serology in plasma samples from 8,746 MS cases and 7,228 controls. We detected increased anti-ANO2 antibody levels in MS (P = 3.5 × 10−36) with 14.6% of cases and 7.8% of controls being ANO2 seropositive (odds ratio [OR] = 1.6; 95% confidence intervals [95%CI]: 1.5 to 1.8). The MS risk increase in ANO2-seropositive individuals was dramatic when also exposed to 3 known risk factors for MS: HLA-DRB1*15:01 carriage, absence of HLA-A*02:01, and high anti-EBNA1 antibody levels (OR = 24.9; 95%CI: 17.9 to 34.8). Reciprocal blocking experiments with ANO2 and EBNA1 peptides demonstrated antibody cross-reactivity, mapping to ANO2 [aa 140 to 149] and EBNA1 [aa 431 to 440]. HLA gene region was associated with anti-ANO2 antibody levels and HLA-DRB1*04:01 haplotype was negatively associated with ANO2 seropositivity (OR = 0.6; 95%CI: 0.5 to 0.7). Anti-ANO2 antibody levels were not increased in patients from 3 other inflammatory disease cohorts. The HLA influence and the fact that specific IgG production usually needs T cell help provides indirect evidence for a T cell ANO2 autoreactivity in MS. We propose a hypothesis where immune reactivity toward EBNA1 through molecular mimicry with ANO2 contributes to the etiopathogenesis of MS.

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.

Ulnar artery vasculopathy: a common but nonspecific feature of systemic sclerosis

2017 ◽  
Vol 2 (3) ◽  
pp. 221-224
Author(s):  
Tae-Jong Kim ◽  
Soon-Young Song ◽  
Hee Chang Ahn ◽  
Yoon-Kyoung Sung ◽  
Sang-Cheol Bae ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Connective Tissue ◽  
Lupus Erythematosus ◽  
Connective Tissue Diseases ◽  
Case Series ◽  
Ulnar Artery ◽  
Common Finding ◽  
Clinical Factors ◽  
Vessel Disease ◽  
Large Vessel Disease

Introduction Systemic sclerosis (SSc) is characterized by microvascular abnormalities and fibrosis. Several studies have reported that large vessel disease is also common in SSc. The aim of this case series was to investigate whether ulnar artery involvement in patients with SSc is a disease-specific phenomenon, as compared to other connective tissue diseases (CTD). Methods A total of 28 patients, including 7 with SSc and 12 with systemic lupus erythematosus (SLE), underwent brachial arteriography due to severe Raynaud's phenomenon and/or digital ulcerations and were enrolled in the study. They were divided into two groups: an SSc/SSc-overlap group and a non-SSc group. The collection of the clinical parameters was conducted to investigate the associations between clinical factors and the ulnar artery vasculopathy. Results The SSc/SSc-overlap group (n = 10) consisted of 7 patients with SSc and 3 with features overlapping SSc. In the non-SSc group (n = 18), 12 cases of SLE, 2 of mixed connective tissue disease, 1 of dermatomyositis + SLE, 1 of rheumatoid arthritis, 1 of Sjogren's syndrome, and 1 case of skin vasculitis, were included. The relative frequencies of ulnar artery involvement were not significantly different between the SSc/SSc-overlap and non-SSc groups, respectively (n = 6, 60% vs. n = 9, 50%, p = 0.611). Conclusions Although ulnar artery involvement was frequently detected in patients with SSc/SSc-overlap, it was also a common finding in other CTDs; therefore, it is not specific to SSc or SSc-overlap diseases.

scholarly journals Epstein-Barr Virus in Systemic Autoimmune Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Anette Holck Draborg ◽  
Karen Duus ◽  
Gunnar Houen
Keyword(s):  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Epstein Barr Virus ◽  
Immune Escape ◽  
Connective Tissue Diseases ◽  
Systemic Autoimmune Diseases ◽  
Barr Virus ◽  
Epstein Barr ◽  
Genetic And Environmental Factors ◽  
Immune Escape Mechanisms

Systemic autoimmune diseases (SADs) are a group of connective tissue diseases with diverse, yet overlapping, symptoms and autoantibody development. The etiology behind SADs is not fully elucidated, but a number of genetic and environmental factors are known to influence the incidence of SADs. Recent findings link dysregulation of Epstein-Barr virus (EBV) with SAD development. EBV causes a persistent infection with a tight latency programme in memory B-cells, which enables evasion of the immune defence. A number of immune escape mechanisms and immune-modulating proteins have been described for EBV. These immune modulating functions make EBV a good candidate for initiation of autoimmune diseases and exacerbation of disease progression. This review focuses on systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and Sjögren’s syndrome (SS) and sum up the existing data linking EBV with these diseases including elevated titres of EBV antibodies, reduced T-cell defence against EBV, and elevated EBV viral load. Together, these data suggest that uncontrolled EBV infection can develop diverse autoreactivities in genetic susceptible individuals with different manifestations depending on the genetic background and the site of reactivation.

scholarly journals Epstein Barr Virus and Autoimmune Responses in Systemic Lupus Erythematosus

2021 ◽  
Vol 11 ◽  
Author(s):  
Neelakshi R. Jog ◽  
Judith A. James
Keyword(s):  
Multiple Sclerosis ◽  
Systemic Lupus Erythematosus ◽  
Systemic Sclerosis ◽  
Lupus Erythematosus ◽  
Epstein Barr Virus ◽  
Immune Dysregulation ◽  
Systemic Autoimmune Disease ◽  
Systemic Lupus ◽  
Barr Virus ◽  
Epstein Barr

Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease. Infections or infectious reactivation are potential triggers for initiation of autoimmunity and for SLE flares. Epstein-Barr virus (EBV) is gamma herpes virus that has been associated with several autoimmune diseases such as SLE, multiple sclerosis, Sjogren’s syndrome, and systemic sclerosis. In this review, we will discuss the recent advances regarding how EBV may contribute to immune dysregulation, and how these mechanisms may relate to SLE disease progression.

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