Biomarkers of lymphoma in Sjögren's syndrome and evaluation of the lymphoma risk in prelymphomatous conditions: results of a multicenter study.
OBJECTIVE
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.
Rheumatology Clinic, DSMB, Department of Medical and Biological Sciences, University Hospital "Santa Maria della Misericordia", Udine, Italy. Electronic address: quarto77@gmail.com.
Luca
L
Quartuccio
Institute of Statistics, University of Udine, Italy.
Miriam
M
Isola
Rheumatology Unit, University of Pisa, Italy.
Chiara
C
Baldini
Rheumatology Unit, La Sapienza University of Rome, Italy.
Roberta
R
Priori
Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Perugia, Italy.
Elena
E
Bartoloni Bocci
Rheumatology Unit, University of L'Aquila, Italy.
Francesco
F
Carubbi
Rheumatology Clinic, DSMB, Department of Medical and Biological Sciences, University Hospital "Santa Maria della Misericordia", Udine, Italy.
Marta
M
Maset
Institute of Statistics, University of Udine, Italy.
Giorgia
G
Gregoraci
Department of Mathematics and Computer Science, University of Udine, Italy.
Vincenzo
V
Della Mea
Rheumatology Clinic, DSMB, Department of Medical and Biological Sciences, University Hospital "Santa Maria della Misericordia", Udine, Italy.
Sara
S
Salvin
Rheumatology Clinic, DSMB, Department of Medical and Biological Sciences, University Hospital "Santa Maria della Misericordia", Udine, Italy.
Ginevra
G
De Marchi
Rheumatology Unit, University of Pisa, Italy.
Nicoletta
N
Luciano
Rheumatology Unit, La Sapienza University of Rome, Italy.
Serena
S
Colafrancesco
Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Perugia, Italy.
Alessia
A
Alunno
Rheumatology Unit, University of L'Aquila, Italy.
Roberto
R
Giacomelli
Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Perugia, Italy.
Roberto
R
Gerli
Rheumatology Unit, La Sapienza University of Rome, Italy.
Guido
G
Valesini
Rheumatology Unit, University of Pisa, Italy.
Stefano
S
Bombardieri
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.
Salvatore
S
De Vita
D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008223:Lymphoma / Q000175:diagnosis* / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D011230:Precancerous Conditions / Q000473:pathology*; D012306:Risk; D012859:Sjogren's Syndrome / Q000150:complications* / Q000276:immunology
D015415:Biomarkers
Cryoglobulinemia; Lymphoma; Sjögren's syndrome