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

For the UK Primary Sjögren's Syndrome registry

doi:10.1093/rheumatology/key063

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

For the UK Primary Sjögren's Syndrome registry

Institute of Cellular Medicine
Newcastle University
University of Birmingham
Binding Site Group
Macquarie University
Rheumatology DepartmentRheumatology Departmentgham NHS Foundation Trust
Cambridge University Hospitals NHS Foundation Trust
Liverpool University Hospitals NHS Foundation Trust
Barking, Havering and Redbridge University Hospitals NHS Trust
Barts Health NHS Trust
Mid and South Essex NHS Foundation Trust
Belfast Health and Social Care Trust
Birmingham Community Healthcare NHS Foundation Trust
Sandwell and West Birmingham Hospitals NHS Trust
University Hospitals Birmingham NHS Foundation Trust
Royal Wolverhampton Hospitals NHS Trust
Leeds Teaching Hospitals NHS Trust
University Hospitals of Derby and Burton NHS Foundation Trust
University Hospitals Plymouth NHS Trust
Dudley Group NHS Foundation Trust
East Kent Hospitals University NHS Foundation Trust
East Sussex Healthcare NHS Trust
Frimley Health NHS Foundation Trust
Harrogate and District NHS Foundation Trust
NHS Greater Glasgow and Clyde
Great Western Hospitals NHS Foundation Trust
Homerton University Hospital NHS Foundation Trust
East Suffolk and North Essex NHS Foundation Trust
Maidstone and Tunbridge Wells NHS Trust
University of Manchester
Newcastle upon Tyne Hospitals NHS Foundation Trust
Nottingham University Hospitals NHS Trust
Portsmouth Hospitals University NHS Trust
Gateshead Health NHS Foundation Trust
Hampshire Hospitals NHS Foundation Trust
Royal United Hospitals Bath NHS Foundation Trust
Royal Sheffield Hospital
South Tyneside and Sunderland NHS Foundation Trust
Royal Surrey Hospital
Salisbury NHS Foundation Trust
Midlands Partnership NHS Foundation Trust
Torbay and South Devon NHS Foundation Trust
University College Hospital
NHS Fife

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

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.

Original language	English
Pages (from-to)	1222-1227
Number of pages	6
Journal	Rheumatology
Volume	57
Issue number	7
DOIs	https://doi.org/10.1093/rheumatology/key063
Publication status	Published - 1 Jul 2018
Externally published	Yes

Keywords

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

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10.1093/rheumatology/key063

Cite this

@article{623bc68af3e541fa9d9d6ad92a983a2b,

title = "B-cell activity markers are associated with different disease activity domains in primary Sj{\"o}gren's syndrome",

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.",

keywords = "B cells, B-cell activating factor, Biomarker, Disease activity, Free light chains, Sj{\"o}gren's syndrome, β-2 microglobulin",

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 Mark Lloyd and Lisa Moore",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology.",

year = "2018",

month = jul,

day = "1",

doi = "10.1093/rheumatology/key063",

language = "English",

volume = "57",

pages = "1222--1227",

journal = "Rheumatology",

issn = "1462-0324",

publisher = "Oxford University Press",

number = "7",

}

TY - JOUR

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,

AU - Mintrim, Kelly

AU - Lloyd, Mark

AU - Moore, Lisa

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

UR - https://www.scopus.com/pages/publications/85051473603

U2 - 10.1093/rheumatology/key063

DO - 10.1093/rheumatology/key063

M3 - Article

C2 - 29608774

AN - SCOPUS:85051473603

SN - 1462-0324

VL - 57

SP - 1222

EP - 1227

JO - Rheumatology

JF - Rheumatology

IS - 7

ER -

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

Abstract

Keywords

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