Objective. The EULAR Sjögren's Syndrome Patient-Reported Index (ESS-PRI) is a validated tool for measuring pain, fatigue and dryness in primary Sjögren's syndrome (pSS). We evaluated its association with disease and non-disease related variables, and its variation though the follow-up. Methods. We included 130 pSS patients who were interviewed to register demographics, schooling, smoking, menopause, body mass index, disease duration, use of hormonal replacement, associated sicca drugs, prednisone, immunosuppressors/antimalarials, comorbidities such as diabetes mellitus, hypothyroidism, depression, fibromyalgia and scored the Charlson comorbidity index. We assessed the non-stimulated whole salivary flow (NSWSF), Schirmer-I test, ESSDAI and ESSPRI scores. In a subset of patients, we scored a second ESSPRI.Results. Most patients were women, mean age 57 years and median disease duration 9.3 years. The median ESSPRI score was 6 (fatigue 6, pain 4, dryness 8). Eighty patients (61.5%) had an ES-SPRI ≥5 points and were characterised by a higher prevalence of depression (OR 3.7,) and lower NSWSF (OR 0.59,. Among 62 patients with a second ESS-PRI (median time 25 months), 44 (70%) experienced a decrement/increment ≥1 in the ESSPRI (16 were decrement). We did not find any of the studied variables associated with this variation, also including change in prednisone or immunosuppressors.Conclusion. An ESSPRI ≥5 (unsatisfactory symptom state) was associated with low NSWSF and depression. Most of the patients experienced a clinically significant ESSPRI variation (increment or decrement), nevertheless, we were not able to identify any variable associated with this change. Further studies would be helpful to understand the underlying causes.

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Diverse immune cell subsets have been described in IgG4-related disease (IgG4-RD). If there is a different immunophenotype according to clinical phenotype and activity status is not known. Levels of IL-4-, IL-13-, IL-5-, and IL-21-producing CD4+ T cells (Th2 subsets), CD4+ cytotoxic T lymphocytes (CD4+CTLs), T helper 9 cells, T follicular helper cells (Tfh; Tfh1/Tfh2/Tfh17/Tf regulatory [Tfr]), Foxp3+ regulatory T cells, Type 1 regulatory T cells (Tr1), T helper 3 regulatory cells (Th3), IL-10-producing regulatory B cells (Bregs), IL-10-expressing regulatory plasmacytoid dendritic (pDC IL-10+) cells, and M1 and M2 monocytes were determined by flow cytometry in 43 IgG4-RD patients and 12 controls. All immune subsets were higher in patients vs. controls. CD4+/IL-4+, CD4+/IL-5+, CD4+CTLs, Tfh2, Tfh17, Tfr, and M1 monocyte cell number was different among IgG4-RD clinical phenotypes. The pancreato-hepato-biliary phenotype was characterized by a higher CD4+CTLs, Tfh17, Tfh2, and Tfr and lower M1 cell number. An increased CD4+CTLs and Th3 cell number distinguished the head and neck-limited phenotype, while the retroperitoneal/aortic and Mikulicz/systemic phenotypes were characterized by increased Th2 subsets. Tfh17, Tr1, Th3, pDC, M1, and M2 monocytes were augmented in active patients. In summary, the clinical heterogeneity of IgG4-RD might be driven by the participation of different immunophenotypes and, consequently, by a different fibroinflammatory process.

Background:The lacrimal gland is frequently involved in both IgG4-related disease (IgG4-RD) and Sjögren’s syndrome (SS) and presents with swelling and/or dry eye symptoms. Although a distinct chemokine and cytokine tear profile might distinguish SS from idiopathic dry eye, as of today no study has assessed this issue in IgG4-RD.Objectives:To evaluate and compare a set of chemokine/cytokine in the tears of patients with IgG4-RD and primary SS.Methods:We included 11 patients with IgG4-RD according to the Comprehensive Diagnostic Criteria for IgG4-RD and 17 with primary SS according the AECG criteria, who attended a tertiary referral center in Mexico City. Schirmer-I test were performed using two standardized sterile tear strips, and then immediately frozen at -86°C until assayed. Once defrosted, the tears were extracted from the strips using a buffer containing 0.5 M NaCl and 0.5% Tween-20. Then, the amount (pg/mL) of the following selected chemokines and cytokines were measured by Luminometry: CCL11, G-CSF, IFN-γ, IL-12p40, IL-12p70, IL-13, IL-17A, IL-1α, IL-1β, IL-4, IL-7, CXCL10, CCL2, CCL3, CCL4 and TNF-α.Results:Patients with IgG4-RD were younger (51.3±14.7 vs. 55.7±10.6) and more frequently men (45.5% vs. 5.9%) than SS patients. Regarding the IgG4-RD group, 7 (63.6%) had lacrimal gland involvement, 5 (45.5%) dry eye symptoms and 6 (54.5%) positive Schirmer-I test. We observed multi-organic involvement in 9 patients (81.8%), median number of involved organs of 5, 9 (81.8%) patients had active disease, median IgG4-RD responder index of 6 points, 8 (72.7%) patients had high IgG4 serum levels, and 9 (81.8%) biopsy proven diagnosis. We found higher levels of IL-7 and CCL2, and a trend for G-CSF in the IgG4-RD group. Conversely, primary SS patients had higher levels of IL-12p40, IL-1α, IL-1β, CCL3 and CCL4. At the logistic regression analysis, the variables that remained associated with IgG4-RD were IL-7 (OR 1.43 95% CI 1.06-1.93, p=0.01) and IL12p40 (OR 0.92, 95% CI 0.84-0.99, p=0.01).In a sensitivity analysis, including only 7 IgG4-RD patients with dacryoadenitis, we also observed higher levels of IL-7 and G-CSF in the IgG4-RD group vs primary SS.Conclusion:The chemokine and cytokine profile of tears of patients with IgG4-RD is characterized by a mixed immune response (Th1/Th2/Th17) compare with a predominantly Th1 response in primary SS. Our results also suggest a possible role of IL-7 in the pathogenesis of IgG4-RD.References:[1] Hernández-Ruiz M, Zlotnik A, Llorente L, Hernandez-Molina G. Markedly high salivary and lacrimal CXCL17 levels in primary Sjögren’s syndrome. Joint Bone Spine. 2018May;85(3):379-380.Table 1: Chemokine/cytokine pg/mL, median(range) IgG4-RD n=11 pSS n=17 p CCL11 11.9 (3.7-34.4)15.4 (3.7-33.0)0.06 G-CSF 118.7 (14.5-325.9)88.5 (14.5-226.5)0.08 IFN-γ 1.3 (0.3-2.1)1.7 (0.01-7.2)0.19 IL-12p40 8.7 (1.3-35.5)24.1 (1.3-69.3)0.02 IL-12p70 0.5 (0.09-3.1)1.6 (0.09-28.1)0.05 IL-13 19.2 (4.6-84.9)18.1 (2.4-75.0)0.30 IL-17A 0.9 (0.2-1.7)0.9 (0.08-4.9)0.89 IL-1α 25.8 (10.5-166.8)54.3 (21.6-119.1)0....