Nancy Agmon-Levin1, Amir Dagan2, Yogev Peri3, Juan-Manuel Anaya4, Carlo Selmi5, Angela Tincani6, Nicola Bizzaro7, Ljudmila Stojanovich8, Jan Damoiseaux9, Jan Willem Cohen Tervaert9, Marta Mosca10, Ricard Cervera11, Yehuda Shoenfeld12. 1. Zabludowicz Center for Autoimmune Diseases, Chaim Sheba Medical Center; and Sackler Faculty of Medicine, Tel-Aviv University, Israel. 2. Zabludowicz Center for Autoimmune Diseases, Chaim Sheba Medical Center; and Internal Medicine T, Chaim Sheba Medical Center, Tel Aviv, Israel. 3. Zabludowicz Center for Autoimmune Diseases, Chaim Sheba Medical Center, Tel Aviv, Israel. 4. Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Colombia. 5. Department of Internal Medicine, IRCCS Istituto Clinico Humanitas, University of Milan, Italy. 6. Rheumatology and Clinical Immunology, Spedali Civili and University of Brescia, Italy. 7. Laboratorio di Patologia Clinica, Ospedale Civile, Tolmezzo, Italy. 8. Bezhanijska Kosa University Medical Center, Serbia. 9. Laboratory of Clinical Immunology, Maastricht University Medical Center, Maastricht, The Netherlands. 10. Department of Clinical and Experimental Medicine, Rheumatology Unit, University of Pisa, Italy. 11. Department of Autoimmune Diseases; Hospital Clínic, Barcelona, Spain. 12. Zabludowicz Center for Autoimmune Diseases, Chaim Sheba Medical Center; Sackler Faculty of Medicine, Tel-Aviv University; and Incumbent of the Laura Schwarz-KipChair for Research of Autoimmune Diseases, Tel-Aviv University, Israel. shoenfel@post.tau.ac.il.
Abstract
OBJECTIVES: The presence of anti-Ro/SSA and anti-La/SSB antibodies has been linked with autoimmunity in general and with several autoimmune diseases (AID) in particular. In the current study we evaluated these antibodies in a wide spectrum of AID as well as the links between them and anti-infectious antibodies. METHODS: We examined 2082 sera from patients with 16 different AID compared to 524 sera from geographically-matched healthy controls, for the presence and titres of anti-Ro/SSA and anti-La/SSB. All samples were also tested for a variety of anti-infectious agents' antibodies using the BioPlex 2200-immunoassay (Bio-Rad, USA). RESULTS: Anti-Ro/SSA was more prevalent, with significantly higher titre in 5 autoimmune diseases namely Sjögren's syndrome (SS), systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS) both primary and APS linked to SLE, systemic sclerosis (SSc) and primary biliary cirrhosis (PBC). Anti-La/SSB was more prevalent with higher titers in SS, SLE, APS linked to SLE and PBC. Prevalence, but not titers, of both antibodies were higher also in polymyositis (PM). Additionally, we found a correlation between anti-Ro/SSA antibodies and antibodies of the IgM and IgG subtypes directed at cytomegalovirus as well as IgG-antibodies directed at Epstein-Barr virus (EBV) and toxoplasma (p<0.001). Anti-La/SSB antibodies correlated with the presence of IgG antibodies against EBV early antigen (p<0.001). CONCLUSIONS: In a large cohort of patients with autoimmune diseases we found an association between anti-Ro/SSA and anti-La/SSB antibodies and 6 autoimmune diseases, amongst which primary APS and PM. Additionally, we observed linkages between these autoantibodies and anti-infectious antibodies directed at Epstein-Barr virus, toxoplasma and cytomegalovirus. Our findings support the concept of interplay between infectious agents and autoimmunity, such as the plausibility of an infectious agent that trigger the immune system to produce specific antibodies which will later result in a unique group of AID.
OBJECTIVES: The presence of anti-Ro/SSA and anti-La/SSB antibodies has been linked with autoimmunity in general and with several autoimmune diseases (AID) in particular. In the current study we evaluated these antibodies in a wide spectrum of AID as well as the links between them and anti-infectious antibodies. METHODS: We examined 2082 sera from patients with 16 different AID compared to 524 sera from geographically-matched healthy controls, for the presence and titres of anti-Ro/SSA and anti-La/SSB. All samples were also tested for a variety of anti-infectious agents' antibodies using the BioPlex 2200-immunoassay (Bio-Rad, USA). RESULTS: Anti-Ro/SSA was more prevalent, with significantly higher titre in 5 autoimmune diseases namely Sjögren's syndrome (SS), systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS) both primary and APS linked to SLE, systemic sclerosis (SSc) and primary biliary cirrhosis (PBC). Anti-La/SSB was more prevalent with higher titers in SS, SLE, APS linked to SLE and PBC. Prevalence, but not titers, of both antibodies were higher also in polymyositis (PM). Additionally, we found a correlation between anti-Ro/SSA antibodies and antibodies of the IgM and IgG subtypes directed at cytomegalovirus as well as IgG-antibodies directed at Epstein-Barr virus (EBV) and toxoplasma (p<0.001). Anti-La/SSB antibodies correlated with the presence of IgG antibodies against EBV early antigen (p<0.001). CONCLUSIONS: In a large cohort of patients with autoimmune diseases we found an association between anti-Ro/SSA and anti-La/SSB antibodies and 6 autoimmune diseases, amongst which primary APS and PM. Additionally, we observed linkages between these autoantibodies and anti-infectious antibodies directed at Epstein-Barr virus, toxoplasma and cytomegalovirus. Our findings support the concept of interplay between infectious agents and autoimmunity, such as the plausibility of an infectious agent that trigger the immune system to produce specific antibodies which will later result in a unique group of AID.
Authors: Harini Bagavant; Micah L Dunkleberger; Nina Wolska; Magdalena Sroka; Astrid Rasmussen; Indra Adrianto; Courtney Montgomery; Kathy Sivils; Joel M Guthridge; Judith A James; Joan T Merrill; Umesh S Deshmukh Journal: Clin Exp Rheumatol Date: 2018-06-25 Impact factor: 4.862