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Tear levels of IL-7, IL-1α, and IL-1β may differentiate between IgG4-related disease and Sjögren’s syndrome

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Abstract

We aim to assess and compare a cytokine and chemokine profile in tears from patients with IgG4-related disease (IgG4-RD) and Sjögren’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 °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-γ, TNF-α, G-CSF, IL-1-α, IL-1β, 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-1α, and IL-1β; in particular, the IL-7/IL-1α and IL-7/IL-1β 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-1α, and IL-1β 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-1α, and IL-1β levels may serve as helpful biomarkers in separating IgG4-RD from SS.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Funding

This study was funded with department resources.

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Correspondence to Luis Llorente.

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The Institutional Review Board (Comité de Ética en Investigación del Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, IRE-2549–18-20–1) approved the study, and it complies with the Helsinki Declaration. Patients signed written informed consent forms.

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Martín-Nares, E., Hernández-Molina, G., Lima, G. et al. Tear levels of IL-7, IL-1α, and IL-1β may differentiate between IgG4-related disease and Sjögren’s syndrome. Clin Rheumatol 42, 1101–1105 (2023). https://doi.org/10.1007/s10067-023-06501-2

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