Tear levels of IL-7, IL-1 alpha, and IL-1 beta may differentiate between IgG4-related disease and Sjogren's syndrome

We aim to assess and compare a cytokine and chemokine profile in tears from patients with IgG4-related disease (IgG4-RD) and Sjogren's syndrome (SS), and to see if this profile could aid in differentiating these two diseases. We included 10 patients with IgG4-RD who met the Comprehensive Diagnostic Criteria for IgG4-RD and 17 patients who met the AECG criteria for primary SS. The Schirmer-I test was carried out using two standardized sterile tear strips, which were then immediately frozen at - 86 degrees C until assayed. The tears were extracted from the strips after they had been defrosted using a buffer containing 0.5 M NaCl and 0.5% Tween-20. The amounts (pg/ml) of the following cytokines and chemokines were then measured using luminometry: IFN-gamma, TNF-alpha, G-CSF, IL-1-alpha, IL-1 beta, IL-4, IL-7, IL-12p40, IL-12p70, IL-13, IL-17A, CCL2, CCL3, CCL4, CCL11, and CXCL10. In the IgG4-RD group, seven patients had lacrimal gland involvement, five had dry eye symptoms, and six had a positive Schirmer-I test. In the SS group, 16 (94.1%) had dry eyes and all had a positive Schirmer-I test. We were able to differentiate between both diseases using levels of IL-7, IL-1 alpha, and IL-1 beta; in particular, the IL-7/IL-1 alpha and IL-7/IL-1 beta ratios had the best discriminatory potential, with cut-off values of 0.32 (AUC: 0.93, sensitivity: 94%, specificity: 80%, p = 0.0003) and 12.55 (AUC: 0.96, sensitivity: 94%, specificity: 90%, p = 0.0001), respectively. Our results suggest that IL-7, IL-1 alpha, and IL-1 beta tear levels could help differentiate IgG4-RD from SS. Key Points The lacrimal gland is frequently involved in IgG4-RD and SS. This characteristic makes both diseases mimics of one another. Patients with IgG4-RD and SS have different profiles of tear cytokines and chemokines. Tear IL-7, IL-1a, and IL-1 beta levels may serve as helpful biomarkers in separating IgG4-RD from SS.