Abstract
Purpose :
Dry eye syndrome (DES) is a manifestation of Sjogren’s syndrome (SS), an autoimmune disease (AID) with a high lifetime risk of B-cell non-Hodgkin lymphoma (B-NHL). We aimed to explore whether an etiologic continuum exists from DES through SS to B-NHL by assessing environmental and infectious exposures and cytokine levels in these disorders.
Methods :
In a clinic-based case-control study 702 participants: 91 SS, 120 DES, 211 controls (age and sex-matched), and 280 B-NHL cases were recruited and interviewed regarding exposures. Antibody titers to HCV, HBV, EBV, CMV, H. pylori, and C. trachomatis were tested by multiplex serology. Serum cytokines IL4, IL6, IL10, IL12, IL17, TNFα, INFγ and IL1β were tested on SS and DES participants using multiplex ELISA.
Results :
SS showed a female predominance (9.2:1). Factors inversely associated with NHL, DES and SS include alcohol consumption (OR=0.47, 95%CI: 0.32-0.71; OR=0.54, CI: 0.33, 0.88; OR=0.27, CI: 0.15, 0.49, respectively), , and East European ancestry for SS (OR=0.43; CI: 0.23-0.79), compared to controls. Self-reported infection requiring hospitalization was more common in NHL (OR=1.91; CI: 1.22-2.98), DES (OR=3.22; CI: 1.93-5.35) and SS (OR=4.58; CI: 2.56-8.18) than in controls. NHL cases were more likely to report 1st degree relatives with hematologic cancer (OR=1.91; CI: 1.00-3.62), while 1st degree relatives with AID were more common among SS (OR=5.23; CI: 2.58-10.58) and DES patients (OR=3.56; CI: 1.84-6.89). IL10 and IL12 levels were higher in SS than in DES, while controls had intermediate levels (P<0.001). A higher proportion of SS patients had antibodies to HCV, EBV-EA-D and CMV (P=0.02, 0.02, 0.01, respectively) than NHL, DES or controls. CMV seropositivity was more common in SS patients than among controls (OR=3.56; CI: 1.14-11.04), while that of C. trachomatis was decreased in DES (OR=0.40; CI: 0.19-0.84) compared to controls.
Conclusions :
While some factors (eg alcohol, hospitalization fir infection) appear to be associated with all 3 conditions, some were specific to one or two of them. Cytokine activation does not show a continuum from controls→DES→SS. Patients with DES and SS appear distinct in terms of infectious exposures. Further work is required to understand events leading to B cell NHL in autoimmune disease.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.