Serological epitope profile of anti-Ro52-positive patients with systemic autoimmune rheumatic diseases

Maria Infantino, Francesca Meacci, Valentina Grossi, Maurizio Benucci, Gabriella Morozzi, Elio Tonutti, Marilina Tampoia, Antonina Ott, Wolfgang Meyer, Fabiola Atzeni, Piercarlo Sarzi-Puttini, Mariangela Manfredi, Nicola Bizzaro

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background: Ro52 is an interferon-inducible protein of the tripartite motif family. Antibodies against Ro52 have been described in patients with different autoimmune diseases, such as systemic lupus erythematosus and Sjögren's syndrome, that are often associated with anti-Ro60 antibodies. The Ro52 autoantigen is extraordinarily immunogenic, and its autoantibodies are directed against both linear and conformational epitopes. The aim of this study was to evaluate the prevalence of antibodies to the five Ro52 domains, as well as to Ro52 176- to 196-amino acid (aa) and 200-239-aa peptides, in different systemic autoimmune rheumatic diseases (SARDs). We also aimed to verify whether antibodies to a single domain or domain association could increase their diagnostic specificity for any SARD. Methods: Serum samples were obtained from 100 anti-Ro52 antibody-positive patients with SARDs and from 68 controls (50 healthy donors and 18 patients with other autoimmune or allergic diseases). A special line immunoassay was created containing a full-length Ro52 antigen expressed in insect cells using the baculovirus system, five recombinant Ro52 antigen fragments [Ro52-1, Ro52-2, Ro52-3, Ro52-4 (partly overlapping Ro52-1 and Ro52-2), and Ro52-5 (partly overlapping Ro52-2 and Ro52-3)], and two Ro52 peptides (176-196 aa and 200-239 aa), all expressed in Escherichia coli. Results: In patients with SARDs, fragment prevalence rates were as follows: Ro52-1 = 3 %, Ro52-2 = 97 %, Ro52-3 = 0 %, Ro52-4 = 9 %, Ro52-5 = 28 %, Ro52 175-196-aa peptide = 6 %, and Ro52 200-239-aa peptide = 74 %. All control samples were negative for the full-length Ro52 and for the five fragments tested. Conclusions: The main epitope of the Ro52 antigen was localized on fragment 2 (aa 125-267), and the majority (97 %) of SARD sera had antibodies that target this fragment. As most of the samples were positive for fragment 2 and only some for fragments 4 or 5, which partially overlap fragment 2, it seems that the target epitope is localized in the middle of fragment 2 or in the area between fragments 4 and 5. No antibody against a single epitope or a combination of epitopes was linked to any of the single SARDs.

Original languageEnglish
Article number365
JournalArthritis Research and Therapy
Volume17
Issue number1
DOIs
Publication statusPublished - Dec 17 2015

Fingerprint

Rheumatic Diseases
Autoimmune Diseases
Epitopes
Amino Acids
Antibodies
Peptides
Anti-Idiotypic Antibodies
Immunoglobulin Fragments
Baculoviridae
Autoantigens
Serum
Immunoassay
Systemic Lupus Erythematosus
Autoantibodies
Interferons
Insects
Tissue Donors
Escherichia coli
SS-A antigen

Keywords

  • Anti-Ro52 antibodies
  • Anti-Ro52 epitopes
  • Rheumatic diseases

ASJC Scopus subject areas

  • Rheumatology
  • Immunology
  • Immunology and Allergy

Cite this

Infantino, M., Meacci, F., Grossi, V., Benucci, M., Morozzi, G., Tonutti, E., ... Bizzaro, N. (2015). Serological epitope profile of anti-Ro52-positive patients with systemic autoimmune rheumatic diseases. Arthritis Research and Therapy, 17(1), [365]. https://doi.org/10.1186/s13075-015-0871-3

Serological epitope profile of anti-Ro52-positive patients with systemic autoimmune rheumatic diseases. / Infantino, Maria; Meacci, Francesca; Grossi, Valentina; Benucci, Maurizio; Morozzi, Gabriella; Tonutti, Elio; Tampoia, Marilina; Ott, Antonina; Meyer, Wolfgang; Atzeni, Fabiola; Sarzi-Puttini, Piercarlo; Manfredi, Mariangela; Bizzaro, Nicola.

In: Arthritis Research and Therapy, Vol. 17, No. 1, 365, 17.12.2015.

Research output: Contribution to journalArticle

Infantino, M, Meacci, F, Grossi, V, Benucci, M, Morozzi, G, Tonutti, E, Tampoia, M, Ott, A, Meyer, W, Atzeni, F, Sarzi-Puttini, P, Manfredi, M & Bizzaro, N 2015, 'Serological epitope profile of anti-Ro52-positive patients with systemic autoimmune rheumatic diseases', Arthritis Research and Therapy, vol. 17, no. 1, 365. https://doi.org/10.1186/s13075-015-0871-3
Infantino, Maria ; Meacci, Francesca ; Grossi, Valentina ; Benucci, Maurizio ; Morozzi, Gabriella ; Tonutti, Elio ; Tampoia, Marilina ; Ott, Antonina ; Meyer, Wolfgang ; Atzeni, Fabiola ; Sarzi-Puttini, Piercarlo ; Manfredi, Mariangela ; Bizzaro, Nicola. / Serological epitope profile of anti-Ro52-positive patients with systemic autoimmune rheumatic diseases. In: Arthritis Research and Therapy. 2015 ; Vol. 17, No. 1.
@article{b0c4e17759264a17ad15b04bbc7d1a87,
title = "Serological epitope profile of anti-Ro52-positive patients with systemic autoimmune rheumatic diseases",
abstract = "Background: Ro52 is an interferon-inducible protein of the tripartite motif family. Antibodies against Ro52 have been described in patients with different autoimmune diseases, such as systemic lupus erythematosus and Sj{\"o}gren's syndrome, that are often associated with anti-Ro60 antibodies. The Ro52 autoantigen is extraordinarily immunogenic, and its autoantibodies are directed against both linear and conformational epitopes. The aim of this study was to evaluate the prevalence of antibodies to the five Ro52 domains, as well as to Ro52 176- to 196-amino acid (aa) and 200-239-aa peptides, in different systemic autoimmune rheumatic diseases (SARDs). We also aimed to verify whether antibodies to a single domain or domain association could increase their diagnostic specificity for any SARD. Methods: Serum samples were obtained from 100 anti-Ro52 antibody-positive patients with SARDs and from 68 controls (50 healthy donors and 18 patients with other autoimmune or allergic diseases). A special line immunoassay was created containing a full-length Ro52 antigen expressed in insect cells using the baculovirus system, five recombinant Ro52 antigen fragments [Ro52-1, Ro52-2, Ro52-3, Ro52-4 (partly overlapping Ro52-1 and Ro52-2), and Ro52-5 (partly overlapping Ro52-2 and Ro52-3)], and two Ro52 peptides (176-196 aa and 200-239 aa), all expressed in Escherichia coli. Results: In patients with SARDs, fragment prevalence rates were as follows: Ro52-1 = 3 {\%}, Ro52-2 = 97 {\%}, Ro52-3 = 0 {\%}, Ro52-4 = 9 {\%}, Ro52-5 = 28 {\%}, Ro52 175-196-aa peptide = 6 {\%}, and Ro52 200-239-aa peptide = 74 {\%}. All control samples were negative for the full-length Ro52 and for the five fragments tested. Conclusions: The main epitope of the Ro52 antigen was localized on fragment 2 (aa 125-267), and the majority (97 {\%}) of SARD sera had antibodies that target this fragment. As most of the samples were positive for fragment 2 and only some for fragments 4 or 5, which partially overlap fragment 2, it seems that the target epitope is localized in the middle of fragment 2 or in the area between fragments 4 and 5. No antibody against a single epitope or a combination of epitopes was linked to any of the single SARDs.",
keywords = "Anti-Ro52 antibodies, Anti-Ro52 epitopes, Rheumatic diseases",
author = "Maria Infantino and Francesca Meacci and Valentina Grossi and Maurizio Benucci and Gabriella Morozzi and Elio Tonutti and Marilina Tampoia and Antonina Ott and Wolfgang Meyer and Fabiola Atzeni and Piercarlo Sarzi-Puttini and Mariangela Manfredi and Nicola Bizzaro",
year = "2015",
month = "12",
day = "17",
doi = "10.1186/s13075-015-0871-3",
language = "English",
volume = "17",
journal = "Arthritis Research and Therapy",
issn = "1478-6354",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Serological epitope profile of anti-Ro52-positive patients with systemic autoimmune rheumatic diseases

AU - Infantino, Maria

AU - Meacci, Francesca

AU - Grossi, Valentina

AU - Benucci, Maurizio

AU - Morozzi, Gabriella

AU - Tonutti, Elio

AU - Tampoia, Marilina

AU - Ott, Antonina

AU - Meyer, Wolfgang

AU - Atzeni, Fabiola

AU - Sarzi-Puttini, Piercarlo

AU - Manfredi, Mariangela

AU - Bizzaro, Nicola

PY - 2015/12/17

Y1 - 2015/12/17

N2 - Background: Ro52 is an interferon-inducible protein of the tripartite motif family. Antibodies against Ro52 have been described in patients with different autoimmune diseases, such as systemic lupus erythematosus and Sjögren's syndrome, that are often associated with anti-Ro60 antibodies. The Ro52 autoantigen is extraordinarily immunogenic, and its autoantibodies are directed against both linear and conformational epitopes. The aim of this study was to evaluate the prevalence of antibodies to the five Ro52 domains, as well as to Ro52 176- to 196-amino acid (aa) and 200-239-aa peptides, in different systemic autoimmune rheumatic diseases (SARDs). We also aimed to verify whether antibodies to a single domain or domain association could increase their diagnostic specificity for any SARD. Methods: Serum samples were obtained from 100 anti-Ro52 antibody-positive patients with SARDs and from 68 controls (50 healthy donors and 18 patients with other autoimmune or allergic diseases). A special line immunoassay was created containing a full-length Ro52 antigen expressed in insect cells using the baculovirus system, five recombinant Ro52 antigen fragments [Ro52-1, Ro52-2, Ro52-3, Ro52-4 (partly overlapping Ro52-1 and Ro52-2), and Ro52-5 (partly overlapping Ro52-2 and Ro52-3)], and two Ro52 peptides (176-196 aa and 200-239 aa), all expressed in Escherichia coli. Results: In patients with SARDs, fragment prevalence rates were as follows: Ro52-1 = 3 %, Ro52-2 = 97 %, Ro52-3 = 0 %, Ro52-4 = 9 %, Ro52-5 = 28 %, Ro52 175-196-aa peptide = 6 %, and Ro52 200-239-aa peptide = 74 %. All control samples were negative for the full-length Ro52 and for the five fragments tested. Conclusions: The main epitope of the Ro52 antigen was localized on fragment 2 (aa 125-267), and the majority (97 %) of SARD sera had antibodies that target this fragment. As most of the samples were positive for fragment 2 and only some for fragments 4 or 5, which partially overlap fragment 2, it seems that the target epitope is localized in the middle of fragment 2 or in the area between fragments 4 and 5. No antibody against a single epitope or a combination of epitopes was linked to any of the single SARDs.

AB - Background: Ro52 is an interferon-inducible protein of the tripartite motif family. Antibodies against Ro52 have been described in patients with different autoimmune diseases, such as systemic lupus erythematosus and Sjögren's syndrome, that are often associated with anti-Ro60 antibodies. The Ro52 autoantigen is extraordinarily immunogenic, and its autoantibodies are directed against both linear and conformational epitopes. The aim of this study was to evaluate the prevalence of antibodies to the five Ro52 domains, as well as to Ro52 176- to 196-amino acid (aa) and 200-239-aa peptides, in different systemic autoimmune rheumatic diseases (SARDs). We also aimed to verify whether antibodies to a single domain or domain association could increase their diagnostic specificity for any SARD. Methods: Serum samples were obtained from 100 anti-Ro52 antibody-positive patients with SARDs and from 68 controls (50 healthy donors and 18 patients with other autoimmune or allergic diseases). A special line immunoassay was created containing a full-length Ro52 antigen expressed in insect cells using the baculovirus system, five recombinant Ro52 antigen fragments [Ro52-1, Ro52-2, Ro52-3, Ro52-4 (partly overlapping Ro52-1 and Ro52-2), and Ro52-5 (partly overlapping Ro52-2 and Ro52-3)], and two Ro52 peptides (176-196 aa and 200-239 aa), all expressed in Escherichia coli. Results: In patients with SARDs, fragment prevalence rates were as follows: Ro52-1 = 3 %, Ro52-2 = 97 %, Ro52-3 = 0 %, Ro52-4 = 9 %, Ro52-5 = 28 %, Ro52 175-196-aa peptide = 6 %, and Ro52 200-239-aa peptide = 74 %. All control samples were negative for the full-length Ro52 and for the five fragments tested. Conclusions: The main epitope of the Ro52 antigen was localized on fragment 2 (aa 125-267), and the majority (97 %) of SARD sera had antibodies that target this fragment. As most of the samples were positive for fragment 2 and only some for fragments 4 or 5, which partially overlap fragment 2, it seems that the target epitope is localized in the middle of fragment 2 or in the area between fragments 4 and 5. No antibody against a single epitope or a combination of epitopes was linked to any of the single SARDs.

KW - Anti-Ro52 antibodies

KW - Anti-Ro52 epitopes

KW - Rheumatic diseases

UR - http://www.scopus.com/inward/record.url?scp=84955684228&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84955684228&partnerID=8YFLogxK

U2 - 10.1186/s13075-015-0871-3

DO - 10.1186/s13075-015-0871-3

M3 - Article

AN - SCOPUS:84955684228

VL - 17

JO - Arthritis Research and Therapy

JF - Arthritis Research and Therapy

SN - 1478-6354

IS - 1

M1 - 365

ER -