Peripheral Immunophenotype in IgG4-Related Disease and Its Association with Clinical Phenotypes and Disease Activity.

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.

Tear levels of IL-7, IL-1α, and IL-1ß may differentiate between IgG4-related disease and Sjögren's syndrome.

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-1ß, 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-1ß; in particular, the IL-7/IL-1α and IL-7/IL-1ß 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-1ß 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-1ß levels may serve as helpful biomarkers in separating IgG4-RD from SS.

Factors influencing the EULAR Sjögren's Syndrome Patient-Reported Index in primary Sjögren's syndrome.

OBJECTIVES: The ESSPRI 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 (BMI), 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 ESSPRI ≥5 points and were characterized by a higher prevalence of depression (OR 3.7, 95% 1.2-11.3) and lower NSWSF (OR 0.59, 95% CI 0.36-0.97). Among 62 patients with a second ESSPRI (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. CONCLUSIONS: 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.