Luca Quartuccio1, Miriam Isola2, Chiara Baldini3, Roberta Priori4, Elena Bartoloni Bocci5, Francesco Carubbi6, Marta Maset7, Giorgia Gregoraci2, Vincenzo Della Mea8, Sara Salvin7, Ginevra De Marchi7, Nicoletta Luciano3, Serena Colafrancesco4, Alessia Alunno5, Roberto Giacomelli6, Roberto Gerli5, Guido Valesini4, Stefano Bombardieri3, Salvatore De Vita9. 1. Rheumatology Clinic, DSMB, Department of Medical and Biological Sciences, University Hospital "Santa Maria della Misericordia", Udine, Italy. Electronic address: quarto77@gmail.com. 2. Institute of Statistics, University of Udine, Italy. 3. Rheumatology Unit, University of Pisa, Italy. 4. Rheumatology Unit, La Sapienza University of Rome, Italy. 5. Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Perugia, Italy. 6. Rheumatology Unit, University of L'Aquila, Italy. 7. Rheumatology Clinic, DSMB, Department of Medical and Biological Sciences, University Hospital "Santa Maria della Misericordia", Udine, Italy. 8. Department of Mathematics and Computer Science, University of Udine, Italy. 9. Rheumatology Clinic, DSMB, Department of Medical and Biological Sciences, University Hospital "Santa Maria della Misericordia", Udine, Italy. Electronic address: devita.salvatore@aoud.sanita.fvg.it.
Abstract
OBJECTIVES: To define the biomarkers associated with lymphoproliferation in primary Sjögren's syndrome (pSS) by distinguishing in separate groups the two best-recognized non-malignant prelymphomatous conditions in pSS, i.e., salivary gland swelling and cryoglobulinemic vasculitis (CV). METHODS: A multicenter study was conducted in 5 centres. Patients fulfilled the following criteria: (1) positive AECG criteria for pSS, (2) serum cryoglobulins evaluated, and (3) lack of hepatitis C virus infection. Four groups were distinguished and analysed by multinomial analyses: (1) B-cell non-Hodgkin's lymphoma (NHL), (2) CV without lymphoma, (3) salivary swelling without NHL (SW), and (4) pSS patients without NHL or prelymphomatous conditions. RESULTS: Six hundred and sixty-one patients were studied. Group 1/NHL comprised 40/661 (6.1%) patients, Group 2/CV 17/661 (2.6%), Group 3/SW 180/661 (27.2%), and Group 4/pSS controls 424/661 (64.1%). Low C4 [relative-risk ratio (RRR) 8.3], cryoglobulins (RRR 6.8), anti-La antibodies (RRR 5.2), and leukopenia (RRR 3.3) were the variables distinguishing Group 1/NHL from Group 4/Controls. As concerns the subset of patients with prelymphomatous conditions, the absence of these biomarkers provided a negative predictive value for lymphoma of 98% in patients with salivary swelling (Group 3/SW). Additional follow-up studies in patients with SW confirmed the high risk of lymphoma when at least 2/4 biomarkers were positive. CONCLUSIONS: Lymphoma-associated biomarkers were defined in a multicentre series of well-characterized patients with pSS, by dissecting the cohort in the pSS-associated prelymphomatous conditions. Notably, it was demonstrated for the first time that among the pSS patients with salivary swelling, only those with positive biomarkers present an increased risk of lymphoma evolution.
OBJECTIVES: To define the biomarkers associated with lymphoproliferation in primary Sjögren's syndrome (pSS) by distinguishing in separate groups the two best-recognized non-malignant prelymphomatous conditions in pSS, i.e., salivary gland swelling and cryoglobulinemic vasculitis (CV). METHODS: A multicenter study was conducted in 5 centres. Patients fulfilled the following criteria: (1) positive AECG criteria for pSS, (2) serum cryoglobulins evaluated, and (3) lack of hepatitis C virus infection. Four groups were distinguished and analysed by multinomial analyses: (1) B-cell non-Hodgkin's lymphoma (NHL), (2) CV without lymphoma, (3) salivary swelling without NHL (SW), and (4) pSS patients without NHL or prelymphomatous conditions. RESULTS: Six hundred and sixty-one patients were studied. Group 1/NHL comprised 40/661 (6.1%) patients, Group 2/CV 17/661 (2.6%), Group 3/SW 180/661 (27.2%), and Group 4/pSS controls 424/661 (64.1%). Low C4 [relative-risk ratio (RRR) 8.3], cryoglobulins (RRR 6.8), anti-La antibodies (RRR 5.2), and leukopenia (RRR 3.3) were the variables distinguishing Group 1/NHL from Group 4/Controls. As concerns the subset of patients with prelymphomatous conditions, the absence of these biomarkers provided a negative predictive value for lymphoma of 98% in patients with salivary swelling (Group 3/SW). Additional follow-up studies in patients with SW confirmed the high risk of lymphoma when at least 2/4 biomarkers were positive. CONCLUSIONS:Lymphoma-associated biomarkers were defined in a multicentre series of well-characterized patients with pSS, by dissecting the cohort in the pSS-associated prelymphomatous conditions. Notably, it was demonstrated for the first time that among the pSS patients with salivary swelling, only those with positive biomarkers present an increased risk of lymphoma evolution.
Authors: Maria B Nishishinya; Claudia A Pereda; Santiago Muñoz-Fernández; José M Pego-Reigosa; Iñigo Rúa-Figueroa; José-Luis Andreu; Mónica Fernández-Castro; José Rosas; Estibaliz Loza Santamaría Journal: Rheumatol Int Date: 2014-06-05 Impact factor: 2.631
Authors: Kerry M Leehan; Nathan P Pezant; Astrid Rasmussen; Kiely Grundahl; Jacen S Moore; Lida Radfar; David M Lewis; Donald U Stone; Christopher J Lessard; Nelson L Rhodus; Barbara M Segal; C Erick Kaufman; R Hal Scofield; Kathy L Sivils; Courtney Montgomery; A Darise Farris Journal: Autoimmunity Date: 2017-10-08 Impact factor: 2.815