Audrey Benyamine1,2, Daniel Bertin3, Noémie Resseguier4, Xavier Heim2,3, Julien Bermudez2, David Launay5,6,7, Sylvain Dubucquoi8, Adrian Hij9, Dominique Farge9,10, Alain Lescoat11, Isabelle Bahon-Riedinger12, Nouria Benmostefa13, Luc Mouthon13, Jean-Robert Harlé14, Gilles Kaplanski2,15, Pascal Rossi1,2, Nathalie Bardin2,3, Brigitte Granel1,2. 1. Internal Medicine Department, North Hospital of Marseilles, Public Assistance Hospital of Marseilles (AP-HM), 13015 Marseilles, France. 2. Aix Marseilles University (AMU), INSERM, INRA, C2VN, 13005 Marseilles, France. 3. Immunology Laboratory, La Conception Hospital, Public Assistance Hospital of Marseilles (AP-HM), 13005 Marseilles, France. 4. Epidemiology and Health Economics, La Timone Hospital, AP-HM, Aix Marseilles University (AMU), 13005 Marseilles, France. 5. Univ. Lille, U1286-INFINITE-Institute for Translational Research in Inflammation, F-59000 Lille, France. 6. Inserm, F-59000 Lille, France. 7. CHU Lille, Internal Medicine and Clinical Immunology Department, Center of Reference for Rare Autoimmune and Systemic Diseases of North and North-West France (CeRAINO), F-59000 Lille, France. 8. Immunology Institute, Hospital University Center of Lille, 59037 Lille, France. 9. Public Assistance Hospital of Paris, Saint-Louis Hospital, Autoimmune and Vascular Disease Unit, Internal Medicine (UF04), Center of reference for rare systemic autoimmune diseases (FAI2R), Université de Paris, EA 3518, Paris, France. 10. Department of Medicine, McGill University, Montreal, QC H3G 2M1, Canada. 11. Internal Medicine and Clinical Immunology Department, Hospital University Center of Rennes, 35000 Rennes, France. 12. Immunology Laboratory, Hospital University Center of Rennes, 35033 Rennes, France. 13. Internal Medicine Department, Center of reference for rare systemic autoimmune diseases of Ile de France, Cochin Hospital, Public Assistance Hospital of Paris (AP-HP), 75014 Paris, France. 14. Internal Medicine Department, La Timone Hospital, Public Assistance Hospital of Marseilles (AP-HM), 13005 Marseilles, France. 15. Internal Medicine and Clinical Immunology Department, La Conception Hospital, Public Assistance Hospital of Marseilles (AP-HM), 13005 Marseilles, France.
Abstract
BACKGROUND: The detection of additional autoantibodies is of great concern in systemic sclerosis (SSc) when those included in the ACR/EULAR classification are negative. In this context, the interest of antifibrillarin (anti-U3RNP) autoantibodies (AFAs) in the routine evaluation of SSc remains unclear. We aimed to assess the relevance of AFAs and their clinical association in SSc patients. METHODS: In a multicenter observational retrospective study, we collected immunological and clinical data associated with AFA positivity in SSc (n = 42) and non-SSc patients (n = 13). Patients with SSc negative for AFAs (n = 83) were considered as a control group. AFAs were detected by indirect immunofluorescence (IIF) using HEp-2 cells, EliA or immunoblot techniques. RESULTS: We confirmed a typical nuclear IIF pattern and showed that AFAs are mostly exclusive towards SSc conventional autoantibodies. Although also observed in non-SSc patients, high levels of AFAs with the ELiA technique allowed the diagnosis of SSc. Compared to AFA-negative SSc patients, AFA-positive SSc patients more frequently exhibited visceral involvements. They more frequently suffered from the diffuse cutaneous form and had a higher global severity of the disease. CONCLUSIONS: We demonstrate the usefulness of quantifying AFAs in the immunological exploration of SSc, especially when patients are seronegative for SSc conventional autoantibodies and display a typical IIF pattern. AFAs might constitute an interesting marker of SSc severity.
BACKGROUND: The detection of additional autoantibodies is of great concern in systemic sclerosis (SSc) when those included in the ACR/EULAR classification are negative. In this context, the interest of antifibrillarin (anti-U3RNP) autoantibodies (AFAs) in the routine evaluation of SSc remains unclear. We aimed to assess the relevance of AFAs and their clinical association in SSc patients. METHODS: In a multicenter observational retrospective study, we collected immunological and clinical data associated with AFA positivity in SSc (n = 42) and non-SSc patients (n = 13). Patients with SSc negative for AFAs (n = 83) were considered as a control group. AFAs were detected by indirect immunofluorescence (IIF) using HEp-2 cells, EliA or immunoblot techniques. RESULTS: We confirmed a typical nuclear IIF pattern and showed that AFAs are mostly exclusive towards SSc conventional autoantibodies. Although also observed in non-SSc patients, high levels of AFAs with the ELiA technique allowed the diagnosis of SSc. Compared to AFA-negative SSc patients, AFA-positive SSc patients more frequently exhibited visceral involvements. They more frequently suffered from the diffuse cutaneous form and had a higher global severity of the disease. CONCLUSIONS: We demonstrate the usefulness of quantifying AFAs in the immunological exploration of SSc, especially when patients are seronegative for SSc conventional autoantibodies and display a typical IIF pattern. AFAs might constitute an interesting marker of SSc severity.