Guillermo Ruacho1,2, Marika Kvarnström1,2, Agneta Zickert1,2, Vilija Oke1,2, Johan Rönnelid1,2, Susanna Eketjäll1,2, Kerstin Elvin1,2, Iva Gunnarsson1,2, Elisabet Svenungsson3,4. 1. From the Department of Medicine Solna, Division of Rheumatology, Karolinska Institutet, Stockholm; Karolinska University Hospital, Stockholm; Karolinska Institutet/AstraZeneca Integrated Cardio Metabolic Centre (KI-AZ ICMC), Stockholm; Department of Medicine Solna, Division of Immunology and Allergy, Karolinska Institutet, Stockholm; Center for Clinical Research, Uppsala University, Sörmland; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala; Cardiovascular, Renal and Metabolism, Innovative Medicines and Early Development (IMED) Biotech Unit, AstraZeneca, Huddinge, Sweden. 2. G. Ruacho, DMD, Department of Medicine Solna, Division of Rheumatology, Karolinska Institutet, and Center for Clinical Research, Uppsala University; M. Kvarnström, MD, PhD, Department of Medicine Solna, Division of Rheumatology, Karolinska Institutet, and Karolinska University Hospital; A. Zickert, MD, PhD, Department of Medicine Solna, Division of Rheumatology, Karolinska Institutet, and Karolinska University Hospital; V. Oke, MD, PhD, Department of Medicine Solna, Division of Rheumatology, Karolinska Institutet, and Karolinska University Hospital; J. Rönnelid, MD, PhD, Department of Immunology, Genetics and Pathology, Uppsala University; S. Eketjäll, PhD, Cardiovascular, Renal and Metabolism, IMED Biotech Unit, AstraZeneca, and KI-AZ ICMC; K. Elvin, MD, PhD, Department of Medicine Solna, Division of Immunology and Allergy, Karolinska Institutet and Karolinska University Hospital; I. Gunnarsson, MD, PhD, Department of Medicine Solna, Division of Rheumatology, Karolinska Institutet, and Karolinska University Hospital; E. Svenungsson, MD, PhD, Department of Medicine Solna, Division of Rheumatology, Karolinska Institutet, and Karolinska University Hospital. 3. From the Department of Medicine Solna, Division of Rheumatology, Karolinska Institutet, Stockholm; Karolinska University Hospital, Stockholm; Karolinska Institutet/AstraZeneca Integrated Cardio Metabolic Centre (KI-AZ ICMC), Stockholm; Department of Medicine Solna, Division of Immunology and Allergy, Karolinska Institutet, Stockholm; Center for Clinical Research, Uppsala University, Sörmland; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala; Cardiovascular, Renal and Metabolism, Innovative Medicines and Early Development (IMED) Biotech Unit, AstraZeneca, Huddinge, Sweden. elisabet.svenungsson@ki.se. 4. G. Ruacho, DMD, Department of Medicine Solna, Division of Rheumatology, Karolinska Institutet, and Center for Clinical Research, Uppsala University; M. Kvarnström, MD, PhD, Department of Medicine Solna, Division of Rheumatology, Karolinska Institutet, and Karolinska University Hospital; A. Zickert, MD, PhD, Department of Medicine Solna, Division of Rheumatology, Karolinska Institutet, and Karolinska University Hospital; V. Oke, MD, PhD, Department of Medicine Solna, Division of Rheumatology, Karolinska Institutet, and Karolinska University Hospital; J. Rönnelid, MD, PhD, Department of Immunology, Genetics and Pathology, Uppsala University; S. Eketjäll, PhD, Cardiovascular, Renal and Metabolism, IMED Biotech Unit, AstraZeneca, and KI-AZ ICMC; K. Elvin, MD, PhD, Department of Medicine Solna, Division of Immunology and Allergy, Karolinska Institutet and Karolinska University Hospital; I. Gunnarsson, MD, PhD, Department of Medicine Solna, Division of Rheumatology, Karolinska Institutet, and Karolinska University Hospital; E. Svenungsson, MD, PhD, Department of Medicine Solna, Division of Rheumatology, Karolinska Institutet, and Karolinska University Hospital. elisabet.svenungsson@ki.se.
Abstract
OBJECTIVE: An often-neglected subset of patients with systemic lupus erythematosus (SLE) is those with secondary Sjögren syndrome (SLE-sSS). Further, primary SS overlaps and can be difficult to delineate from SLE. To shed light on the SLE-sSS subset, we investigated a large and well-characterized SLE cohort, comparing patients with SLE-sSS and SLE patients without SS (SLE-nonsSS) and controls. METHODS: We included 504 consecutive patients with SLE, fulfilling the 1982 revised American College of Rheumatology criteria, and 319 controls from the general population, matched for age and sex to the first 319 patients. SLE-sSS was defined according to the American-European Consensus Criteria (AECC). A thorough clinical examination, including subjective and objective quantifications of sicca symptoms, was performed in all participants. Autoantibodies and 20 selected cytokines were measured by luminex and multiplex analysis, respectively. RESULTS: SLE-sSS, as defined by AECC, occurred in 23% of the patients with SLE. In comparison to SLE-nonsSS, the SLE-sSS group was older and more frequently female. Leukopenia and peripheral neuropathy were more frequent and nephritis less frequent. Circulating levels of 6/20 investigated proinflammatory cytokines [tumor necrosis factor-α, interleukin (IL) 6, monocyte chemoattractant protein 4, macrophage inflammatory protein 1β, IL-12/IL-23p40, and interferon γ-induced protein 10], total IgG, anti-SSA/Ro52, anti-SSA/Ro60, anti-SSB/La antibodies, and rheumatoid factor (IgM and IgA) were higher in the SLE-sSS group (p < 0.05 for all comparisons). CONCLUSION: The frequency of SLE-sSS increased with age and affected roughly one-quarter of all patients with SLE. Despite less internal organ involvement, a systemic inflammatory state with high levels of proinflammatory cytokines is present in the SLE-sSS subgroup. This is a novel observation that may affect future understanding and treatment of the SLE-sSS subset.
OBJECTIVE: An often-neglected subset of patients with systemic lupus erythematosus (SLE) is those with secondary Sjögren syndrome (SLE-sSS). Further, primary SS overlaps and can be difficult to delineate from SLE. To shed light on the SLE-sSS subset, we investigated a large and well-characterized SLE cohort, comparing patients with SLE-sSS and SLEpatients without SS (SLE-nonsSS) and controls. METHODS: We included 504 consecutive patients with SLE, fulfilling the 1982 revised American College of Rheumatology criteria, and 319 controls from the general population, matched for age and sex to the first 319 patients. SLE-sSS was defined according to the American-European Consensus Criteria (AECC). A thorough clinical examination, including subjective and objective quantifications of sicca symptoms, was performed in all participants. Autoantibodies and 20 selected cytokines were measured by luminex and multiplex analysis, respectively. RESULTS:SLE-sSS, as defined by AECC, occurred in 23% of the patients with SLE. In comparison to SLE-nonsSS, the SLE-sSS group was older and more frequently female. Leukopenia and peripheral neuropathy were more frequent and nephritis less frequent. Circulating levels of 6/20 investigated proinflammatory cytokines [tumor necrosis factor-α, interleukin (IL) 6, monocyte chemoattractant protein 4, macrophage inflammatory protein 1β, IL-12/IL-23p40, and interferon γ-induced protein 10], total IgG, anti-SSA/Ro52, anti-SSA/Ro60, anti-SSB/La antibodies, and rheumatoid factor (IgM and IgA) were higher in the SLE-sSS group (p < 0.05 for all comparisons). CONCLUSION: The frequency of SLE-sSS increased with age and affected roughly one-quarter of all patients with SLE. Despite less internal organ involvement, a systemic inflammatory state with high levels of proinflammatory cytokines is present in the SLE-sSS subgroup. This is a novel observation that may affect future understanding and treatment of the SLE-sSS subset.
Authors: Elisabet Svenungsson; Iva Gunnarsson; Vera Illescas-Bäckelin; Estelle Trysberg; Andreas Jönsen; Dag Leonard; Christopher Sjöwall; Susanne Pettersson Journal: Lupus Sci Med Date: 2021-05
Authors: Sahwa Elbagir; Giorgia Grosso; NasrEldeen A Mohammed; Amir I Elshafie; Elnour M Elagib; Agneta Zickert; Vivek Anand Manivel; Eleftheria Pertsinidou; Musa A M Nur; Iva Gunnarsson; Johan Rönnelid; Elisabet Svenungsson Journal: Lupus Date: 2021-05-06 Impact factor: 2.911
Authors: M Paula Gomez Hernandez; Emily E Starman; Andrew B Davis; Miyuraj Harishchandra Hikkaduwa Withanage; Erliang Zeng; Scott M Lieberman; Kim A Brogden; Emily A Lanzel Journal: Rheumatology (Oxford) Date: 2021-10-02 Impact factor: 7.580