Hadas Ben-Eli1,2,3, Abraham Solomon1, Doron J Aframian4, Eldad Ben-Chetrit5, Dror Mevorach6, Geffen Kleinstern7, Tim Waterboer8, Martina Willhauck-Fleckenstein8, Michael Pawlita8, Ora Paltiel2,9. 1. Braun School of Public Health and Community Medicine, Hadassah-Hebrew University, Jerusalem, Israel. 2. Department of Ophthalmology Hadassah-Hebrew University Medical Center, Jerusalem, Israel. 3. Department of Optometry and Vision Science, Hadassah Academic College, Jerusalem, Israel. 4. Department of Oral Medicine, Sedation and Maxillofacial Imaging and Sjogren's Syndrome Center, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. 5. Unit of Rheumatology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. 6. Department of Internal Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. 7. Department of Health Sciences Research, Mayo Clinic, Rochester, MN, United States of America. 8. Infections and Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. 9. Department of Hematology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
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.
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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