Smoking, Porphyromonas gingivalis and the immune response to citrullinated autoantigens before the clinical onset of rheumatoid arthritis in a Southern European nested case-control study

Benjamin A Fisher; Alison J Cartwright; Anne-Marie Quirke; Paola de Pablo; Dora Romaguera; Salvatore Panico; Amalia Mattiello; Diana Gavrila; Carmen Navarro; Carlotta Sacerdote; Paolo Vineis; Rosario Tumino; David F Lappin; Danae Apazidou; Shauna Culshaw; Jan Potempa; Dominique S Michaud; Elio Riboli; Patrick J Venables

doi:10.1186/s12891-015-0792-y

Smoking, Porphyromonas gingivalis and the immune response to citrullinated autoantigens before the clinical onset of rheumatoid arthritis in a Southern European nested case-control study

Benjamin A Fisher, Alison J Cartwright, Anne-Marie Quirke, Paola de Pablo, Dora Romaguera, Salvatore Panico, Amalia Mattiello, Diana Gavrila, Carmen Navarro, Carlotta Sacerdote, Paolo Vineis, Rosario Tumino, David F Lappin, Danae Apazidou, Shauna Culshaw, Jan Potempa, Dominique S Michaud, Elio Riboli, Patrick J Venables

Inflammation and Ageing

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Abstract

BACKGROUND: Antibodies to citrullinated proteins (ACPA) occur years before RA diagnosis. Porphyromonas gingivalis expresses its own peptidylarginine deiminase (PPAD), and is a proposed aetiological factor for the ACPA response. Smoking is a risk factor for both ACPA-positive RA and periodontitis. We aimed to study the relation of these factors to the risk of RA in a prospective cohort.

METHODS: We performed a nested case-control study by identifying pre-RA cases in four populations from the European Prospective Investigation into Cancer and nutrition, matched with three controls. Data on smoking and other covariates were obtained from baseline questionnaires. Antibodies to CCP2 and citrullinated peptides from α-enolase, fibrinogen, vimentin and PPAD were measured. Antibodies to arginine gingipain (RgpB) were used as a marker for P.gingivalis infection and validated in a separate cohort of healthy controls and subjects with periodontitis.

RESULTS: We studied 103 pre-RA cases. RA development was associated with several ACPA specificities, but not with antibodies to citrullinated PPAD peptides. Antibody levels to RgpB and PPAD peptides were higher in smokers but were not associated with risk of RA or with pre-RA autoimmunity. Former but not current smoking was associated with antibodies to α-enolase (OR 4.06; 95 % CI 1.02, 16.2 versus 0.54; 0.09-3.73) and fibrinogen peptides (OR 4.24; 95 % CI 1.2-14.96 versus 0.58; 0.13-2.70), and later development of RA (OR 2.48; 95 % CI 1.27-4.84 versus 1.57; 0.85-2.93), independent of smoking intensity.

CONCLUSIONS: Smoking remains a risk factor for RA well before the clinical onset of disease. In this cohort, P.gingivalis is not associated with pre-RA autoimmunity or risk of RA in an early phase before disease-onset. Antibodies to PPAD peptides are not an early feature of ACPA ontogeny.

Original language	English
Article number	331
Journal	BMC Musculoskeletal Disorders
Volume	16
Issue number	1
DOIs	https://doi.org/10.1186/s12891-015-0792-y
Publication status	Published - 4 Nov 2015

Keywords

Smoking
Rheumatoid arthritis (RA)
Anti-citrullinated protein antibodies (ACPA)
Citrullination
Porphyromonas gingivalis

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1186/s12891-015-0792-yLicence: Creative Commons: Attribution (CC BY)

Fisher_et_al_Smoking_porphyromonas_BMC_Musculoskeletal_disorders_2015
Checked for eligibility: 20/01/2016. © 2015 Fisher et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Final published version, 702 KBLicence: Creative Commons: Attribution (CC BY)

Cite this

Fisher, B. A., Cartwright, A. J., Quirke, A.-M., de Pablo, P., Romaguera, D., Panico, S., Mattiello, A., Gavrila, D., Navarro, C., Sacerdote, C., Vineis, P., Tumino, R., Lappin, D. F., Apazidou, D., Culshaw, S., Potempa, J., Michaud, D. S., Riboli, E., & Venables, P. J. (2015). Smoking, Porphyromonas gingivalis and the immune response to citrullinated autoantigens before the clinical onset of rheumatoid arthritis in a Southern European nested case-control study. BMC Musculoskeletal Disorders, 16(1), Article 331. https://doi.org/10.1186/s12891-015-0792-y

@article{053f60bba4fa4bc0a2aea4b47d15c52f,

title = "Smoking, Porphyromonas gingivalis and the immune response to citrullinated autoantigens before the clinical onset of rheumatoid arthritis in a Southern European nested case-control study",

abstract = "BACKGROUND: Antibodies to citrullinated proteins (ACPA) occur years before RA diagnosis. Porphyromonas gingivalis expresses its own peptidylarginine deiminase (PPAD), and is a proposed aetiological factor for the ACPA response. Smoking is a risk factor for both ACPA-positive RA and periodontitis. We aimed to study the relation of these factors to the risk of RA in a prospective cohort.METHODS: We performed a nested case-control study by identifying pre-RA cases in four populations from the European Prospective Investigation into Cancer and nutrition, matched with three controls. Data on smoking and other covariates were obtained from baseline questionnaires. Antibodies to CCP2 and citrullinated peptides from α-enolase, fibrinogen, vimentin and PPAD were measured. Antibodies to arginine gingipain (RgpB) were used as a marker for P.gingivalis infection and validated in a separate cohort of healthy controls and subjects with periodontitis.RESULTS: We studied 103 pre-RA cases. RA development was associated with several ACPA specificities, but not with antibodies to citrullinated PPAD peptides. Antibody levels to RgpB and PPAD peptides were higher in smokers but were not associated with risk of RA or with pre-RA autoimmunity. Former but not current smoking was associated with antibodies to α-enolase (OR 4.06; 95 % CI 1.02, 16.2 versus 0.54; 0.09-3.73) and fibrinogen peptides (OR 4.24; 95 % CI 1.2-14.96 versus 0.58; 0.13-2.70), and later development of RA (OR 2.48; 95 % CI 1.27-4.84 versus 1.57; 0.85-2.93), independent of smoking intensity.CONCLUSIONS: Smoking remains a risk factor for RA well before the clinical onset of disease. In this cohort, P.gingivalis is not associated with pre-RA autoimmunity or risk of RA in an early phase before disease-onset. Antibodies to PPAD peptides are not an early feature of ACPA ontogeny.",

keywords = "Smoking, Rheumatoid arthritis (RA), Anti-citrullinated protein antibodies (ACPA), Citrullination, Porphyromonas gingivalis",

author = "Fisher, {Benjamin A} and Cartwright, {Alison J} and Anne-Marie Quirke and {de Pablo}, Paola and Dora Romaguera and Salvatore Panico and Amalia Mattiello and Diana Gavrila and Carmen Navarro and Carlotta Sacerdote and Paolo Vineis and Rosario Tumino and Lappin, {David F} and Danae Apazidou and Shauna Culshaw and Jan Potempa and Michaud, {Dominique S} and Elio Riboli and Venables, {Patrick J}",

year = "2015",

month = nov,

day = "4",

doi = "10.1186/s12891-015-0792-y",

language = "English",

volume = "16",

journal = "BMC Musculoskeletal Disorders",

issn = "1471-2474",

publisher = "Springer",

number = "1",

}

Fisher, BA, Cartwright, AJ, Quirke, A-M, de Pablo, P, Romaguera, D, Panico, S, Mattiello, A, Gavrila, D, Navarro, C, Sacerdote, C, Vineis, P, Tumino, R, Lappin, DF, Apazidou, D, Culshaw, S, Potempa, J, Michaud, DS, Riboli, E & Venables, PJ 2015, 'Smoking, Porphyromonas gingivalis and the immune response to citrullinated autoantigens before the clinical onset of rheumatoid arthritis in a Southern European nested case-control study', BMC Musculoskeletal Disorders, vol. 16, no. 1, 331. https://doi.org/10.1186/s12891-015-0792-y

Smoking, Porphyromonas gingivalis and the immune response to citrullinated autoantigens before the clinical onset of rheumatoid arthritis in a Southern European nested case-control study. / Fisher, Benjamin A; Cartwright, Alison J; Quirke, Anne-Marie et al.
In: BMC Musculoskeletal Disorders, Vol. 16, No. 1, 331, 04.11.2015.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Smoking, Porphyromonas gingivalis and the immune response to citrullinated autoantigens before the clinical onset of rheumatoid arthritis in a Southern European nested case-control study

AU - Fisher, Benjamin A

AU - Cartwright, Alison J

AU - Quirke, Anne-Marie

AU - de Pablo, Paola

AU - Romaguera, Dora

AU - Panico, Salvatore

AU - Mattiello, Amalia

AU - Gavrila, Diana

AU - Navarro, Carmen

AU - Sacerdote, Carlotta

AU - Vineis, Paolo

AU - Tumino, Rosario

AU - Lappin, David F

AU - Apazidou, Danae

AU - Culshaw, Shauna

AU - Potempa, Jan

AU - Michaud, Dominique S

AU - Riboli, Elio

AU - Venables, Patrick J

PY - 2015/11/4

Y1 - 2015/11/4

N2 - BACKGROUND: Antibodies to citrullinated proteins (ACPA) occur years before RA diagnosis. Porphyromonas gingivalis expresses its own peptidylarginine deiminase (PPAD), and is a proposed aetiological factor for the ACPA response. Smoking is a risk factor for both ACPA-positive RA and periodontitis. We aimed to study the relation of these factors to the risk of RA in a prospective cohort.METHODS: We performed a nested case-control study by identifying pre-RA cases in four populations from the European Prospective Investigation into Cancer and nutrition, matched with three controls. Data on smoking and other covariates were obtained from baseline questionnaires. Antibodies to CCP2 and citrullinated peptides from α-enolase, fibrinogen, vimentin and PPAD were measured. Antibodies to arginine gingipain (RgpB) were used as a marker for P.gingivalis infection and validated in a separate cohort of healthy controls and subjects with periodontitis.RESULTS: We studied 103 pre-RA cases. RA development was associated with several ACPA specificities, but not with antibodies to citrullinated PPAD peptides. Antibody levels to RgpB and PPAD peptides were higher in smokers but were not associated with risk of RA or with pre-RA autoimmunity. Former but not current smoking was associated with antibodies to α-enolase (OR 4.06; 95 % CI 1.02, 16.2 versus 0.54; 0.09-3.73) and fibrinogen peptides (OR 4.24; 95 % CI 1.2-14.96 versus 0.58; 0.13-2.70), and later development of RA (OR 2.48; 95 % CI 1.27-4.84 versus 1.57; 0.85-2.93), independent of smoking intensity.CONCLUSIONS: Smoking remains a risk factor for RA well before the clinical onset of disease. In this cohort, P.gingivalis is not associated with pre-RA autoimmunity or risk of RA in an early phase before disease-onset. Antibodies to PPAD peptides are not an early feature of ACPA ontogeny.

AB - BACKGROUND: Antibodies to citrullinated proteins (ACPA) occur years before RA diagnosis. Porphyromonas gingivalis expresses its own peptidylarginine deiminase (PPAD), and is a proposed aetiological factor for the ACPA response. Smoking is a risk factor for both ACPA-positive RA and periodontitis. We aimed to study the relation of these factors to the risk of RA in a prospective cohort.METHODS: We performed a nested case-control study by identifying pre-RA cases in four populations from the European Prospective Investigation into Cancer and nutrition, matched with three controls. Data on smoking and other covariates were obtained from baseline questionnaires. Antibodies to CCP2 and citrullinated peptides from α-enolase, fibrinogen, vimentin and PPAD were measured. Antibodies to arginine gingipain (RgpB) were used as a marker for P.gingivalis infection and validated in a separate cohort of healthy controls and subjects with periodontitis.RESULTS: We studied 103 pre-RA cases. RA development was associated with several ACPA specificities, but not with antibodies to citrullinated PPAD peptides. Antibody levels to RgpB and PPAD peptides were higher in smokers but were not associated with risk of RA or with pre-RA autoimmunity. Former but not current smoking was associated with antibodies to α-enolase (OR 4.06; 95 % CI 1.02, 16.2 versus 0.54; 0.09-3.73) and fibrinogen peptides (OR 4.24; 95 % CI 1.2-14.96 versus 0.58; 0.13-2.70), and later development of RA (OR 2.48; 95 % CI 1.27-4.84 versus 1.57; 0.85-2.93), independent of smoking intensity.CONCLUSIONS: Smoking remains a risk factor for RA well before the clinical onset of disease. In this cohort, P.gingivalis is not associated with pre-RA autoimmunity or risk of RA in an early phase before disease-onset. Antibodies to PPAD peptides are not an early feature of ACPA ontogeny.

KW - Smoking

KW - Rheumatoid arthritis (RA)

KW - Anti-citrullinated protein antibodies (ACPA)

KW - Citrullination

KW - Porphyromonas gingivalis

U2 - 10.1186/s12891-015-0792-y

DO - 10.1186/s12891-015-0792-y

M3 - Article

C2 - 26537917

SN - 1471-2474

VL - 16

JO - BMC Musculoskeletal Disorders

JF - BMC Musculoskeletal Disorders

IS - 1

M1 - 331

ER -

Smoking, Porphyromonas gingivalis and the immune response to citrullinated autoantigens before the clinical onset of rheumatoid arthritis in a Southern European nested case-control study

Abstract

Keywords

UN SDGs

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