Recognition of new citrulline-containing peptide epitopes by autoantibodies produced in vivo and in vitro by B cells of rheumatoid arthritis patients

Eszter Szarka, Fruzsina Babos, Anna Magyar, Krisztina Huber, Zoltán Szittner, Krisztián Papp, J. Prechl, Judit Pozsgay, Zsuzsa Neer, Monika Ádori, György Nagy, Bernadette Rojkovich, Tamás Gáti, Judit Kelemen, Zsuzsanna Baka, Márta Brózik, Borbála Pazár, G. Poór, F. Hudecz, G. Sármay

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Anti-citrullinated peptide/protein antibodies (ACPAs) are highly sensitive and specific markers of rheumatoid arthritis (RA). Identification of peptide epitopes that may detect different subgroups of RA patients might have diagnostic and prognostic significance. We have investigated citrulline- and arginine-containing peptide pairs derived from filaggrin, collagen or vimentin, and compared this citrulline-peptide panel with the serological assays conventionally used to detect ACPAs. Furthermore, we studied if the same citrulline-peptides identify antibody-secreting cells in in vitro cultures of RA B cells. Recognition of citrulline- and arginine-containing filaggrin, vimentin and collagen peptide epitopes were tested by Multipin ELISA system, by indirect ELISA and by a peptide-specific microarray. B cells were purified from blood by negative selection; antibody-producing cells were enumerated by ELISPOT assay. The panel composed of citrulline-peptide epitopes of filaggrin, collagen and vimentin was recognized by RA sera with a sensitivity and specificity comparable with the currently used tests. Moreover, the combined citrulline-peptide panel including the new short epitope peptide of filaggrin, fil311-315, also identified nearly one-third of RA cases that were negative for antibodies against cyclic citrullinated peptides, mutated citrullinated vimentin or for rheumatoid factor. The results with the peptide-specific microarray have shown that although most ACPAs recognizing the four citrulline peptides are IgG, some of them specifically recognizing citrulline-containing filaggrin peptides (fil311-315 and fil306-326) are IgM, and so may be produced either by newly formed activated B cells or by unswitched B memory cells. Furthermore, the citrulline-peptides of filaggrin and vimentin detect ACPA-producing cells, and so could also be applied to study the B cells of RA patients.

Original languageEnglish
Pages (from-to)181-191
Number of pages11
JournalImmunology
Volume141
Issue number2
DOIs
Publication statusPublished - Feb 2014

Fingerprint

Citrulline
Autoantibodies
Epitopes
Rheumatoid Arthritis
B-Lymphocytes
Peptides
Vimentin
Antibody-Producing Cells
In Vitro Techniques
Collagen
Antibodies
Arginine
Proteins
Enzyme-Linked Immunosorbent Assay
Enzyme-Linked Immunospot Assay
Rheumatoid Factor

Keywords

  • Anti-citrullinated peptide antibodies
  • B cell
  • Citrulline-peptide
  • Diagnosis
  • Rheumatoid arthritis

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Recognition of new citrulline-containing peptide epitopes by autoantibodies produced in vivo and in vitro by B cells of rheumatoid arthritis patients. / Szarka, Eszter; Babos, Fruzsina; Magyar, Anna; Huber, Krisztina; Szittner, Zoltán; Papp, Krisztián; Prechl, J.; Pozsgay, Judit; Neer, Zsuzsa; Ádori, Monika; Nagy, György; Rojkovich, Bernadette; Gáti, Tamás; Kelemen, Judit; Baka, Zsuzsanna; Brózik, Márta; Pazár, Borbála; Poór, G.; Hudecz, F.; Sármay, G.

In: Immunology, Vol. 141, No. 2, 02.2014, p. 181-191.

Research output: Contribution to journalArticle

Szarka, E, Babos, F, Magyar, A, Huber, K, Szittner, Z, Papp, K, Prechl, J, Pozsgay, J, Neer, Z, Ádori, M, Nagy, G, Rojkovich, B, Gáti, T, Kelemen, J, Baka, Z, Brózik, M, Pazár, B, Poór, G, Hudecz, F & Sármay, G 2014, 'Recognition of new citrulline-containing peptide epitopes by autoantibodies produced in vivo and in vitro by B cells of rheumatoid arthritis patients', Immunology, vol. 141, no. 2, pp. 181-191. https://doi.org/10.1111/imm.12175
Szarka, Eszter ; Babos, Fruzsina ; Magyar, Anna ; Huber, Krisztina ; Szittner, Zoltán ; Papp, Krisztián ; Prechl, J. ; Pozsgay, Judit ; Neer, Zsuzsa ; Ádori, Monika ; Nagy, György ; Rojkovich, Bernadette ; Gáti, Tamás ; Kelemen, Judit ; Baka, Zsuzsanna ; Brózik, Márta ; Pazár, Borbála ; Poór, G. ; Hudecz, F. ; Sármay, G. / Recognition of new citrulline-containing peptide epitopes by autoantibodies produced in vivo and in vitro by B cells of rheumatoid arthritis patients. In: Immunology. 2014 ; Vol. 141, No. 2. pp. 181-191.
@article{2665e3fc19b14844b9f3afe8ae912fbb,
title = "Recognition of new citrulline-containing peptide epitopes by autoantibodies produced in vivo and in vitro by B cells of rheumatoid arthritis patients",
abstract = "Anti-citrullinated peptide/protein antibodies (ACPAs) are highly sensitive and specific markers of rheumatoid arthritis (RA). Identification of peptide epitopes that may detect different subgroups of RA patients might have diagnostic and prognostic significance. We have investigated citrulline- and arginine-containing peptide pairs derived from filaggrin, collagen or vimentin, and compared this citrulline-peptide panel with the serological assays conventionally used to detect ACPAs. Furthermore, we studied if the same citrulline-peptides identify antibody-secreting cells in in vitro cultures of RA B cells. Recognition of citrulline- and arginine-containing filaggrin, vimentin and collagen peptide epitopes were tested by Multipin ELISA system, by indirect ELISA and by a peptide-specific microarray. B cells were purified from blood by negative selection; antibody-producing cells were enumerated by ELISPOT assay. The panel composed of citrulline-peptide epitopes of filaggrin, collagen and vimentin was recognized by RA sera with a sensitivity and specificity comparable with the currently used tests. Moreover, the combined citrulline-peptide panel including the new short epitope peptide of filaggrin, fil311-315, also identified nearly one-third of RA cases that were negative for antibodies against cyclic citrullinated peptides, mutated citrullinated vimentin or for rheumatoid factor. The results with the peptide-specific microarray have shown that although most ACPAs recognizing the four citrulline peptides are IgG, some of them specifically recognizing citrulline-containing filaggrin peptides (fil311-315 and fil306-326) are IgM, and so may be produced either by newly formed activated B cells or by unswitched B memory cells. Furthermore, the citrulline-peptides of filaggrin and vimentin detect ACPA-producing cells, and so could also be applied to study the B cells of RA patients.",
keywords = "Anti-citrullinated peptide antibodies, B cell, Citrulline-peptide, Diagnosis, Rheumatoid arthritis",
author = "Eszter Szarka and Fruzsina Babos and Anna Magyar and Krisztina Huber and Zolt{\'a}n Szittner and Kriszti{\'a}n Papp and J. Prechl and Judit Pozsgay and Zsuzsa Neer and Monika {\'A}dori and Gy{\"o}rgy Nagy and Bernadette Rojkovich and Tam{\'a}s G{\'a}ti and Judit Kelemen and Zsuzsanna Baka and M{\'a}rta Br{\'o}zik and Borb{\'a}la Paz{\'a}r and G. Po{\'o}r and F. Hudecz and G. S{\'a}rmay",
year = "2014",
month = "2",
doi = "10.1111/imm.12175",
language = "English",
volume = "141",
pages = "181--191",
journal = "Immunology",
issn = "0019-2805",
publisher = "Wiley-Blackwell",
number = "2",

}

TY - JOUR

T1 - Recognition of new citrulline-containing peptide epitopes by autoantibodies produced in vivo and in vitro by B cells of rheumatoid arthritis patients

AU - Szarka, Eszter

AU - Babos, Fruzsina

AU - Magyar, Anna

AU - Huber, Krisztina

AU - Szittner, Zoltán

AU - Papp, Krisztián

AU - Prechl, J.

AU - Pozsgay, Judit

AU - Neer, Zsuzsa

AU - Ádori, Monika

AU - Nagy, György

AU - Rojkovich, Bernadette

AU - Gáti, Tamás

AU - Kelemen, Judit

AU - Baka, Zsuzsanna

AU - Brózik, Márta

AU - Pazár, Borbála

AU - Poór, G.

AU - Hudecz, F.

AU - Sármay, G.

PY - 2014/2

Y1 - 2014/2

N2 - Anti-citrullinated peptide/protein antibodies (ACPAs) are highly sensitive and specific markers of rheumatoid arthritis (RA). Identification of peptide epitopes that may detect different subgroups of RA patients might have diagnostic and prognostic significance. We have investigated citrulline- and arginine-containing peptide pairs derived from filaggrin, collagen or vimentin, and compared this citrulline-peptide panel with the serological assays conventionally used to detect ACPAs. Furthermore, we studied if the same citrulline-peptides identify antibody-secreting cells in in vitro cultures of RA B cells. Recognition of citrulline- and arginine-containing filaggrin, vimentin and collagen peptide epitopes were tested by Multipin ELISA system, by indirect ELISA and by a peptide-specific microarray. B cells were purified from blood by negative selection; antibody-producing cells were enumerated by ELISPOT assay. The panel composed of citrulline-peptide epitopes of filaggrin, collagen and vimentin was recognized by RA sera with a sensitivity and specificity comparable with the currently used tests. Moreover, the combined citrulline-peptide panel including the new short epitope peptide of filaggrin, fil311-315, also identified nearly one-third of RA cases that were negative for antibodies against cyclic citrullinated peptides, mutated citrullinated vimentin or for rheumatoid factor. The results with the peptide-specific microarray have shown that although most ACPAs recognizing the four citrulline peptides are IgG, some of them specifically recognizing citrulline-containing filaggrin peptides (fil311-315 and fil306-326) are IgM, and so may be produced either by newly formed activated B cells or by unswitched B memory cells. Furthermore, the citrulline-peptides of filaggrin and vimentin detect ACPA-producing cells, and so could also be applied to study the B cells of RA patients.

AB - Anti-citrullinated peptide/protein antibodies (ACPAs) are highly sensitive and specific markers of rheumatoid arthritis (RA). Identification of peptide epitopes that may detect different subgroups of RA patients might have diagnostic and prognostic significance. We have investigated citrulline- and arginine-containing peptide pairs derived from filaggrin, collagen or vimentin, and compared this citrulline-peptide panel with the serological assays conventionally used to detect ACPAs. Furthermore, we studied if the same citrulline-peptides identify antibody-secreting cells in in vitro cultures of RA B cells. Recognition of citrulline- and arginine-containing filaggrin, vimentin and collagen peptide epitopes were tested by Multipin ELISA system, by indirect ELISA and by a peptide-specific microarray. B cells were purified from blood by negative selection; antibody-producing cells were enumerated by ELISPOT assay. The panel composed of citrulline-peptide epitopes of filaggrin, collagen and vimentin was recognized by RA sera with a sensitivity and specificity comparable with the currently used tests. Moreover, the combined citrulline-peptide panel including the new short epitope peptide of filaggrin, fil311-315, also identified nearly one-third of RA cases that were negative for antibodies against cyclic citrullinated peptides, mutated citrullinated vimentin or for rheumatoid factor. The results with the peptide-specific microarray have shown that although most ACPAs recognizing the four citrulline peptides are IgG, some of them specifically recognizing citrulline-containing filaggrin peptides (fil311-315 and fil306-326) are IgM, and so may be produced either by newly formed activated B cells or by unswitched B memory cells. Furthermore, the citrulline-peptides of filaggrin and vimentin detect ACPA-producing cells, and so could also be applied to study the B cells of RA patients.

KW - Anti-citrullinated peptide antibodies

KW - B cell

KW - Citrulline-peptide

KW - Diagnosis

KW - Rheumatoid arthritis

UR - http://www.scopus.com/inward/record.url?scp=84891897803&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84891897803&partnerID=8YFLogxK

U2 - 10.1111/imm.12175

DO - 10.1111/imm.12175

M3 - Article

VL - 141

SP - 181

EP - 191

JO - Immunology

JF - Immunology

SN - 0019-2805

IS - 2

ER -