B-cell activity markers are associated with different disease activity domains in primary Sjögren's syndrome

for the UK Primary Sjögren's Syndrome Registry, Katherine James, Chimwemwe Chipeta, Antony Parker, Stephen Harding, Simon J. Cockell, Colin S. Gillespie, Jennifer Hallinan, Francesca Barone, Simon J. Bowman, Wan Fai Ng, Benjamin A. Fisher, Frances Hall, Elalaine C. Bacabac, Helen Frankland, Robert Moots, Kuntal Chadravarty, Shamin Lamabadusuriya, Michele Bombardieri, Constantino Pitzalis & 31 others Nurhan Sutcliffe, Celia Breston, Nagui Gendi, Karen Culfear, Claire Riddell, John Hamburger, Andrea Richards, Saaeha Rauz, Sue Brailsford, Joanne Dasgin, Joanne Logan, Diarmuid Mulherin, Jacqueline Andrews, Paul Emery, Alison McManus, Colin Pease, David Pickles, Alison Booth, Marian Regan, Jon King, Amanda Holt, Theodoros Dimitroulas, Lucy Kadiki, Daljit Kaur, George Kitas, Abdul Khan, Tracey Cosier, Panthakalam, Kelly Mintrim, Neil McHugh, John Pauling

Research output: Contribution to journalArticle

Abstract

Objectives. B-cell activating factor (BAFF), β-2 microglobulin (β2M) and serum free light chains (FLCs) are elevated in primary SS (pSS) and associated with disease activity. We aimed to investigate their association with the individual disease activity domains of the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) in a large well-characterized pSS cohort. Methods. Sera from pSS patients enrolled in the UK Primary Sjögren's Syndrome Registry (UKPSSR) (n = 553) and healthy controls (n = 286) were analysed for FLC (κ and λ), BAFF and β2M. Pearson correlation coefficients were calculated for patient clinical characteristics, including salivary flow, Schirmer's test, EULAR Sjögren's Syndrome Patient Reported Index and serum IgG levels. Poisson regression was performed to identify independent predictors of total ESSDAI and ClinESSDAI (validated ESSDAI minus the biological domain) scores and their domains. Results. Levels of BAFF, β2M and FLCs were higher in pSS patients compared to controls. All three biomarkers associated significantly with the ESSDAI and the ClinESSDAI. BAFF associated with the peripheral nervous system domain of the ESSDAI, whereas β2M and FLCs associated with the cutaneous, biological and renal domains. Multivariate analysis showed BAFF, β2M and their interaction to be independent predictors of ESSDAI/ClinESSDAI. FLCs were also shown to associate with the ESSDAI/ ClinESSDAI but not independent of serum IgG. Conclusion. All biomarkers were associated with total ESSDAI scores but with differing domain associations. These findings should encourage further investigation of these biomarkers in longitudinal studies and against other disease activity measures.

LanguageEnglish
Pages1222-1227
Number of pages6
JournalRheumatology (United Kingdom)
Volume57
Issue number7
Early online date28 Mar 2018
DOIs
StatusPublished - 1 Jul 2018

Keywords

  • B cells
  • B-cell activating factor
  • Biomarker
  • Disease activity
  • Free light chains
  • Sjögren's syndrome
  • β-2 microglobulin

ASJC Scopus subject areas

  • Rheumatology
  • Pharmacology (medical)

Cite this

B-cell activity markers are associated with different disease activity domains in primary Sjögren's syndrome. / for the UK Primary Sjögren's Syndrome Registry.

In: Rheumatology (United Kingdom), Vol. 57, No. 7, 01.07.2018, p. 1222-1227.

Research output: Contribution to journalArticle

for the UK Primary Sjögren's Syndrome Registry. / B-cell activity markers are associated with different disease activity domains in primary Sjögren's syndrome. In: Rheumatology (United Kingdom). 2018 ; Vol. 57, No. 7. pp. 1222-1227.
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abstract = "Objectives. B-cell activating factor (BAFF), β-2 microglobulin (β2M) and serum free light chains (FLCs) are elevated in primary SS (pSS) and associated with disease activity. We aimed to investigate their association with the individual disease activity domains of the EULAR Sj{\"o}gren's Syndrome Disease Activity Index (ESSDAI) in a large well-characterized pSS cohort. Methods. Sera from pSS patients enrolled in the UK Primary Sj{\"o}gren's Syndrome Registry (UKPSSR) (n = 553) and healthy controls (n = 286) were analysed for FLC (κ and λ), BAFF and β2M. Pearson correlation coefficients were calculated for patient clinical characteristics, including salivary flow, Schirmer's test, EULAR Sj{\"o}gren's Syndrome Patient Reported Index and serum IgG levels. Poisson regression was performed to identify independent predictors of total ESSDAI and ClinESSDAI (validated ESSDAI minus the biological domain) scores and their domains. Results. Levels of BAFF, β2M and FLCs were higher in pSS patients compared to controls. All three biomarkers associated significantly with the ESSDAI and the ClinESSDAI. BAFF associated with the peripheral nervous system domain of the ESSDAI, whereas β2M and FLCs associated with the cutaneous, biological and renal domains. Multivariate analysis showed BAFF, β2M and their interaction to be independent predictors of ESSDAI/ClinESSDAI. FLCs were also shown to associate with the ESSDAI/ ClinESSDAI but not independent of serum IgG. Conclusion. All biomarkers were associated with total ESSDAI scores but with differing domain associations. These findings should encourage further investigation of these biomarkers in longitudinal studies and against other disease activity measures.",
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author = "{for the UK Primary Sj{\"o}gren's Syndrome Registry} and Katherine James and Chimwemwe Chipeta and Antony Parker and Stephen Harding and Cockell, {Simon J.} and Gillespie, {Colin S.} and Jennifer Hallinan and Francesca Barone and Bowman, {Simon J.} and Ng, {Wan Fai} and Fisher, {Benjamin A.} and Frances Hall and Bacabac, {Elalaine C.} and Helen Frankland and Robert Moots and Kuntal Chadravarty and Shamin Lamabadusuriya and Michele Bombardieri and Constantino Pitzalis and Nurhan Sutcliffe and Celia Breston and Nagui Gendi and Karen Culfear and Claire Riddell and John Hamburger and Andrea Richards and Saaeha Rauz and Sue Brailsford and Joanne Dasgin and Joanne Logan and Diarmuid Mulherin and Jacqueline Andrews and Paul Emery and Alison McManus and Colin Pease and David Pickles and Alison Booth and Marian Regan and Jon King and Amanda Holt and Theodoros Dimitroulas and Lucy Kadiki and Daljit Kaur and George Kitas and Abdul Khan and Tracey Cosier and Panthakalam and Kelly Mintrim and Neil McHugh and John Pauling",
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T1 - B-cell activity markers are associated with different disease activity domains in primary Sjögren's syndrome

AU - for the UK Primary Sjögren's Syndrome Registry

AU - James, Katherine

AU - Chipeta, Chimwemwe

AU - Parker, Antony

AU - Harding, Stephen

AU - Cockell, Simon J.

AU - Gillespie, Colin S.

AU - Hallinan, Jennifer

AU - Barone, Francesca

AU - Bowman, Simon J.

AU - Ng, Wan Fai

AU - Fisher, Benjamin A.

AU - Hall, Frances

AU - Bacabac, Elalaine C.

AU - Frankland, Helen

AU - Moots, Robert

AU - Chadravarty, Kuntal

AU - Lamabadusuriya, Shamin

AU - Bombardieri, Michele

AU - Pitzalis, Constantino

AU - Sutcliffe, Nurhan

AU - Breston, Celia

AU - Gendi, Nagui

AU - Culfear, Karen

AU - Riddell, Claire

AU - Hamburger, John

AU - Richards, Andrea

AU - Rauz, Saaeha

AU - Brailsford, Sue

AU - Dasgin, Joanne

AU - Logan, Joanne

AU - Mulherin, Diarmuid

AU - Andrews, Jacqueline

AU - Emery, Paul

AU - McManus, Alison

AU - Pease, Colin

AU - Pickles, David

AU - Booth, Alison

AU - Regan, Marian

AU - King, Jon

AU - Holt, Amanda

AU - Dimitroulas, Theodoros

AU - Kadiki, Lucy

AU - Kaur, Daljit

AU - Kitas, George

AU - Khan, Abdul

AU - Cosier, Tracey

AU - Panthakalam, null

AU - Mintrim, Kelly

AU - McHugh, Neil

AU - Pauling, John

PY - 2018/7/1

Y1 - 2018/7/1

N2 - Objectives. B-cell activating factor (BAFF), β-2 microglobulin (β2M) and serum free light chains (FLCs) are elevated in primary SS (pSS) and associated with disease activity. We aimed to investigate their association with the individual disease activity domains of the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) in a large well-characterized pSS cohort. Methods. Sera from pSS patients enrolled in the UK Primary Sjögren's Syndrome Registry (UKPSSR) (n = 553) and healthy controls (n = 286) were analysed for FLC (κ and λ), BAFF and β2M. Pearson correlation coefficients were calculated for patient clinical characteristics, including salivary flow, Schirmer's test, EULAR Sjögren's Syndrome Patient Reported Index and serum IgG levels. Poisson regression was performed to identify independent predictors of total ESSDAI and ClinESSDAI (validated ESSDAI minus the biological domain) scores and their domains. Results. Levels of BAFF, β2M and FLCs were higher in pSS patients compared to controls. All three biomarkers associated significantly with the ESSDAI and the ClinESSDAI. BAFF associated with the peripheral nervous system domain of the ESSDAI, whereas β2M and FLCs associated with the cutaneous, biological and renal domains. Multivariate analysis showed BAFF, β2M and their interaction to be independent predictors of ESSDAI/ClinESSDAI. FLCs were also shown to associate with the ESSDAI/ ClinESSDAI but not independent of serum IgG. Conclusion. All biomarkers were associated with total ESSDAI scores but with differing domain associations. These findings should encourage further investigation of these biomarkers in longitudinal studies and against other disease activity measures.

AB - Objectives. B-cell activating factor (BAFF), β-2 microglobulin (β2M) and serum free light chains (FLCs) are elevated in primary SS (pSS) and associated with disease activity. We aimed to investigate their association with the individual disease activity domains of the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) in a large well-characterized pSS cohort. Methods. Sera from pSS patients enrolled in the UK Primary Sjögren's Syndrome Registry (UKPSSR) (n = 553) and healthy controls (n = 286) were analysed for FLC (κ and λ), BAFF and β2M. Pearson correlation coefficients were calculated for patient clinical characteristics, including salivary flow, Schirmer's test, EULAR Sjögren's Syndrome Patient Reported Index and serum IgG levels. Poisson regression was performed to identify independent predictors of total ESSDAI and ClinESSDAI (validated ESSDAI minus the biological domain) scores and their domains. Results. Levels of BAFF, β2M and FLCs were higher in pSS patients compared to controls. All three biomarkers associated significantly with the ESSDAI and the ClinESSDAI. BAFF associated with the peripheral nervous system domain of the ESSDAI, whereas β2M and FLCs associated with the cutaneous, biological and renal domains. Multivariate analysis showed BAFF, β2M and their interaction to be independent predictors of ESSDAI/ClinESSDAI. FLCs were also shown to associate with the ESSDAI/ ClinESSDAI but not independent of serum IgG. Conclusion. All biomarkers were associated with total ESSDAI scores but with differing domain associations. These findings should encourage further investigation of these biomarkers in longitudinal studies and against other disease activity measures.

KW - B cells

KW - B-cell activating factor

KW - Biomarker

KW - Disease activity

KW - Free light chains

KW - Sjögren's syndrome

KW - β-2 microglobulin

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U2 - 10.1093/rheumatology/key063

DO - 10.1093/rheumatology/key063

M3 - Article

VL - 57

SP - 1222

EP - 1227

JO - Rheumatology

T2 - Rheumatology

JF - Rheumatology

SN - 1462-0324

IS - 7

ER -