Serological and hematological characteristics of Sjogren’s syndrome and dry eye syndrome patients using a novel immune serology technique

Hadas Ben-Eli; Abraham Solomon; Doron J. Aframian; Eldad Ben-Chetrit; Dror Mevorach; Geffen Kleinstern; Tim Waterboer; Martina Willhauck-Fleckenstein; Michael Pawlita; Ora Paltiel

doi:10.1371/journal.pone.0244712

Serological and hematological characteristics of Sjogren’s syndrome and dry eye syndrome patients using a novel immune serology technique

Hadas Ben-Eli^*, Abraham Solomon, Doron J. Aframian, Eldad Ben-Chetrit, Dror Mevorach, Geffen Kleinstern, Tim Waterboer, Martina Willhauck-Fleckenstein, Michael Pawlita, Ora Paltiel

^*Corresponding author for this work

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

3 Scopus citations

Abstract

Objectives To compare hematologic and serological parameters among patients with Sjogren’s syndrome (SS), dry eye syndrome (DES) and controls, and validate a novel multiplex-serology method for identifying auto-antibodies in these populations. Methods In a clinic-based case-control study a total of 422 participants were recruited, including 91 with SS, 120 DES, and 211 controls (age and sex frequency-matched). We measured blood counts, anti-nuclear-antibodies (ANA), anti-SSA/SSB, anti-ribonucleoprotein (RNP), anti-double-stranded-DNA (DS-DNA), and rheumatoid factor (RF) using the “Immunodot” qualitative-ELISA assay. Immunoglobulins, C3 and C4 were measured by immune-fluorescence. Autoantibodies were also quantified with a newly-developed method using glutathione-S-transferase fusion proteins of SSA/Ro 52 and 60kD and SSB/La (multiplex-serology), measuring median fluorescence intensity (MFI). Results Among DES patients, only 2% (95%CI: 0.36–6.3) had positive immune serology. SS patients had lower lymphocyte, hemoglobin and C3 levels but higher prevalence of RF, ANA, anti-SSA/B and higher IgG and MFI levels, compared to DES and controls (P<0.001). Presence of anti-SSA/Ro-52kD was associated with SS [odds ratio (OR) = 2.05, 95% confidence interval (CI): 1.46–2.88]. Anti-SSB/La was inversely associated with DES (OR = 0.81, 95%CI: 0.65–1.00) compared to controls. Positivity to RF (adjusted for age, gender and ethnicity OR = 5.03, 95%CI: 1.78–14.21), ANA (OR = 14.75, 95%CI: 4.09–53.17), or combination of anti-SSA/B (OR = 20.97, 95%CI: 4.60–95.54) were more likely in SS compared to DES. The novel multiplex-serology method correctly identified anti-SSA/B autoantibodies by ELISA among SS, DES patients and controls (sensitivity = 1.0, negative-predictive-value = 1.0). Conclusions Serologic parameters distinguish SS from DES patients and controls. A newly-developed multiplex-serology technique may be useful to detect autoantibodies in large epidemiologic studies.

Original language	American English
Article number	e0244712
Journal	PLoS ONE
Volume	15
Issue number	12 December
DOIs	https://doi.org/10.1371/journal.pone.0244712
State	Published - Dec 2020

Bibliographical note

Funding Information:
The study was supported by the ?Israel Cancer Association? (grant number: 8037815 to OP) https://en.cancer.org.il/ The funders do not play any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Publisher Copyright:
© 2020 Ben-Eli et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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10.1371/journal.pone.0244712

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Ben-Eli, H., Solomon, A., Aframian, D. J., Ben-Chetrit, E., Mevorach, D., Kleinstern, G., Waterboer, T., Willhauck-Fleckenstein, M., Pawlita, M., & Paltiel, O. (2020). Serological and hematological characteristics of Sjogren’s syndrome and dry eye syndrome patients using a novel immune serology technique. PLoS ONE, 15(12 December), Article e0244712. https://doi.org/10.1371/journal.pone.0244712

@article{44f0de124ce74b9eaa6a33d354e60726,

title = "Serological and hematological characteristics of Sjogren{\textquoteright}s syndrome and dry eye syndrome patients using a novel immune serology technique",

abstract = "Objectives To compare hematologic and serological parameters among patients with Sjogren{\textquoteright}s syndrome (SS), dry eye syndrome (DES) and controls, and validate a novel multiplex-serology method for identifying auto-antibodies in these populations. Methods In a clinic-based case-control study a total of 422 participants were recruited, including 91 with SS, 120 DES, and 211 controls (age and sex frequency-matched). We measured blood counts, anti-nuclear-antibodies (ANA), anti-SSA/SSB, anti-ribonucleoprotein (RNP), anti-double-stranded-DNA (DS-DNA), and rheumatoid factor (RF) using the “Immunodot” qualitative-ELISA assay. Immunoglobulins, C3 and C4 were measured by immune-fluorescence. Autoantibodies were also quantified with a newly-developed method using glutathione-S-transferase fusion proteins of SSA/Ro 52 and 60kD and SSB/La (multiplex-serology), measuring median fluorescence intensity (MFI). Results Among DES patients, only 2% (95%CI: 0.36–6.3) had positive immune serology. SS patients had lower lymphocyte, hemoglobin and C3 levels but higher prevalence of RF, ANA, anti-SSA/B and higher IgG and MFI levels, compared to DES and controls (P<0.001). Presence of anti-SSA/Ro-52kD was associated with SS [odds ratio (OR) = 2.05, 95% confidence interval (CI): 1.46–2.88]. Anti-SSB/La was inversely associated with DES (OR = 0.81, 95%CI: 0.65–1.00) compared to controls. Positivity to RF (adjusted for age, gender and ethnicity OR = 5.03, 95%CI: 1.78–14.21), ANA (OR = 14.75, 95%CI: 4.09–53.17), or combination of anti-SSA/B (OR = 20.97, 95%CI: 4.60–95.54) were more likely in SS compared to DES. The novel multiplex-serology method correctly identified anti-SSA/B autoantibodies by ELISA among SS, DES patients and controls (sensitivity = 1.0, negative-predictive-value = 1.0). Conclusions Serologic parameters distinguish SS from DES patients and controls. A newly-developed multiplex-serology technique may be useful to detect autoantibodies in large epidemiologic studies.",

author = "Hadas Ben-Eli and Abraham Solomon and Aframian, {Doron J.} and Eldad Ben-Chetrit and Dror Mevorach and Geffen Kleinstern and Tim Waterboer and Martina Willhauck-Fleckenstein and Michael Pawlita and Ora Paltiel",

note = "Funding Information: The study was supported by the ?Israel Cancer Association? (grant number: 8037815 to OP) https://en.cancer.org.il/ The funders do not play any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: {\textcopyright} 2020 Ben-Eli et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",

year = "2020",

month = dec,

doi = "10.1371/journal.pone.0244712",

language = "American English",

volume = "15",

journal = "PLoS ONE",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "12 December",

}

Ben-Eli, H, Solomon, A, Aframian, DJ, Ben-Chetrit, E, Mevorach, D, Kleinstern, G, Waterboer, T, Willhauck-Fleckenstein, M, Pawlita, M & Paltiel, O 2020, 'Serological and hematological characteristics of Sjogren’s syndrome and dry eye syndrome patients using a novel immune serology technique', PLoS ONE, vol. 15, no. 12 December, e0244712. https://doi.org/10.1371/journal.pone.0244712

TY - JOUR

T1 - Serological and hematological characteristics of Sjogren’s syndrome and dry eye syndrome patients using a novel immune serology technique

AU - Ben-Eli, Hadas

AU - Solomon, Abraham

AU - Aframian, Doron J.

AU - Ben-Chetrit, Eldad

AU - Mevorach, Dror

AU - Kleinstern, Geffen

AU - Waterboer, Tim

AU - Willhauck-Fleckenstein, Martina

AU - Pawlita, Michael

AU - Paltiel, Ora

N1 - Funding Information: The study was supported by the ?Israel Cancer Association? (grant number: 8037815 to OP) https://en.cancer.org.il/ The funders do not play any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: © 2020 Ben-Eli et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PY - 2020/12

Y1 - 2020/12

N2 - Objectives To compare hematologic and serological parameters among patients with Sjogren’s syndrome (SS), dry eye syndrome (DES) and controls, and validate a novel multiplex-serology method for identifying auto-antibodies in these populations. Methods In a clinic-based case-control study a total of 422 participants were recruited, including 91 with SS, 120 DES, and 211 controls (age and sex frequency-matched). We measured blood counts, anti-nuclear-antibodies (ANA), anti-SSA/SSB, anti-ribonucleoprotein (RNP), anti-double-stranded-DNA (DS-DNA), and rheumatoid factor (RF) using the “Immunodot” qualitative-ELISA assay. Immunoglobulins, C3 and C4 were measured by immune-fluorescence. Autoantibodies were also quantified with a newly-developed method using glutathione-S-transferase fusion proteins of SSA/Ro 52 and 60kD and SSB/La (multiplex-serology), measuring median fluorescence intensity (MFI). Results Among DES patients, only 2% (95%CI: 0.36–6.3) had positive immune serology. SS patients had lower lymphocyte, hemoglobin and C3 levels but higher prevalence of RF, ANA, anti-SSA/B and higher IgG and MFI levels, compared to DES and controls (P<0.001). Presence of anti-SSA/Ro-52kD was associated with SS [odds ratio (OR) = 2.05, 95% confidence interval (CI): 1.46–2.88]. Anti-SSB/La was inversely associated with DES (OR = 0.81, 95%CI: 0.65–1.00) compared to controls. Positivity to RF (adjusted for age, gender and ethnicity OR = 5.03, 95%CI: 1.78–14.21), ANA (OR = 14.75, 95%CI: 4.09–53.17), or combination of anti-SSA/B (OR = 20.97, 95%CI: 4.60–95.54) were more likely in SS compared to DES. The novel multiplex-serology method correctly identified anti-SSA/B autoantibodies by ELISA among SS, DES patients and controls (sensitivity = 1.0, negative-predictive-value = 1.0). Conclusions Serologic parameters distinguish SS from DES patients and controls. A newly-developed multiplex-serology technique may be useful to detect autoantibodies in large epidemiologic studies.

AB - Objectives To compare hematologic and serological parameters among patients with Sjogren’s syndrome (SS), dry eye syndrome (DES) and controls, and validate a novel multiplex-serology method for identifying auto-antibodies in these populations. Methods In a clinic-based case-control study a total of 422 participants were recruited, including 91 with SS, 120 DES, and 211 controls (age and sex frequency-matched). We measured blood counts, anti-nuclear-antibodies (ANA), anti-SSA/SSB, anti-ribonucleoprotein (RNP), anti-double-stranded-DNA (DS-DNA), and rheumatoid factor (RF) using the “Immunodot” qualitative-ELISA assay. Immunoglobulins, C3 and C4 were measured by immune-fluorescence. Autoantibodies were also quantified with a newly-developed method using glutathione-S-transferase fusion proteins of SSA/Ro 52 and 60kD and SSB/La (multiplex-serology), measuring median fluorescence intensity (MFI). Results Among DES patients, only 2% (95%CI: 0.36–6.3) had positive immune serology. SS patients had lower lymphocyte, hemoglobin and C3 levels but higher prevalence of RF, ANA, anti-SSA/B and higher IgG and MFI levels, compared to DES and controls (P<0.001). Presence of anti-SSA/Ro-52kD was associated with SS [odds ratio (OR) = 2.05, 95% confidence interval (CI): 1.46–2.88]. Anti-SSB/La was inversely associated with DES (OR = 0.81, 95%CI: 0.65–1.00) compared to controls. Positivity to RF (adjusted for age, gender and ethnicity OR = 5.03, 95%CI: 1.78–14.21), ANA (OR = 14.75, 95%CI: 4.09–53.17), or combination of anti-SSA/B (OR = 20.97, 95%CI: 4.60–95.54) were more likely in SS compared to DES. The novel multiplex-serology method correctly identified anti-SSA/B autoantibodies by ELISA among SS, DES patients and controls (sensitivity = 1.0, negative-predictive-value = 1.0). Conclusions Serologic parameters distinguish SS from DES patients and controls. A newly-developed multiplex-serology technique may be useful to detect autoantibodies in large epidemiologic studies.

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U2 - 10.1371/journal.pone.0244712

DO - 10.1371/journal.pone.0244712

M3 - Article

C2 - 33382786

AN - SCOPUS:85099044633

SN - 1932-6203

VL - 15

JO - PLoS ONE

JF - PLoS ONE

IS - 12 December

M1 - e0244712

ER -

Serological and hematological characteristics of Sjogren’s syndrome and dry eye syndrome patients using a novel immune serology technique

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