CD4 T lymphocyte autophagy is upregulated in the salivary glands of primary Sjögren’s syndrome patients and correlates with focus score and disease activity

Background: Primary Sjögren’s syndrome (pSS) is a common chronic autoimmune disease characterized by lymphocytic infiltration of exocrine glands and peripheral lymphocyte perturbation. In the current study, we aimed to investigate the possible pathogenic implication of autophagy in T lymphocytes in patients with pSS. Methods: Thirty consecutive pSS patients were recruited together with 20 patients affected by sicca syndrome a nd/or chronic sialoadenitis and 30 healthy controls. Disease activity and damage were evaluated according to SS disease activity index, EULAR SS disease activity index, and SS disease damage index. T lymphocytes were analyzed for the expression of autophagy-specific markers by biochemical, molecular, and histological assays in peripheral blood and labial gland biopsies. Serum interleukin (IL)-23 and IL-21 levels were quantified by enzyme-linked immunosorbent assay. Results: Our study provides evidence for the first time that autophagy is upregulated in CD4+ T lymphocyte salivary glands from pSS patients. Furthermore, a statistically significant correlation was detected between lymphocyte autophagy levels, disease activity, and damage indexes. We also found a positive correlation between autophagy enhancement and the increased salivary gland expression of IL-21 and IL-23, providing a further link between innate and adaptive immune responses in pSS. Conclusions: These findings suggest that CD4+ T lymphocyte autophagy could play a key role in pSS pathogenesis. Additionally, our data highlight the potential exploitation of T cell autophagy as a biomarker of disease activity and provide new ground to verify the therapeutic implications of autophagy as an innovative drug target in pSS

Diabetes-Related Autoantibodies in Children With Acute Lymphoblastic Leukemia

[No abstract available

Characterization and outcomes of 414 patients with primary SS who developed haematological malignancies

Objective: To characterize 414 patients with primary SS who developed haematological malignancies and to analyse how the main SS- and lymphoma-related features can modify the presentation patterns and outcomes. Methods: By January 2021, the Big Data Sjögren Project Consortium database included 11 966 patients fulfilling the 2002/2016 classification criteria. Haematological malignancies diagnosed according to the World Health Organization (WHO) classification were retrospectively identified. Results: There were 414 patients (355 women, mean age 57 years) with haematological malignancies (in 43, malignancy preceded at least one year the SS diagnosis). A total of 376 (91%) patients had mature B-cell malignancy, nearly half had extranodal marginal zone lymphoma (MZL) of mucosa-associated lymphoid tissue (MALT lymphoma) (n = 197), followed by diffuse large B-cell lymphoma (DLBCL) (n = 67), nodal MZL lymphoma (n = 29), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) (n = 19) and follicular lymphoma (FL) (n = 17). Rates of complete response, relapses and death were 80%, 34% and 13%, respectively, with a 5-year survival rate of 86.5% after a mean follow-up of 8 years. There were significant differences in age at diagnosis (younger in MALT, older in CLL/SLL), predominant clinical presentation (glandular enlargement in MALT lymphoma, peripheral lymphadenopathy in nodal MZL and FL, constitutional symptoms in DLBCL, incidental diagnosis in CLL/SLL), therapeutic response (higher in MALT lymphoma, lower in DLBCL) and survival (better in MALT, nodal MZL and FL, worse in DLBCL). Conclusion: In the largest reported study of haematological malignancies complicating primary SS, we confirm the overwhelming predominance of B-cell lymphomas, especially MALT, with the salivary glands being the primary site of involvement. This highly-specific histopathological scenario is linked with the overall good prognosis with a 5-year survival rate of nearly 90%

Left Ventricular Function in Insulin-Dependent and in Non-Insulin-Dependent Diabetic Patients: Radionuclide Assessment.

The aim of this study was to compare, by gated radionuclide angiography, systolic and diastolic ventricular function in insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetic patients without overt cardiovascular disease. The study population consisted of 20 IDDM patients (15 male, 5 female; 40.7 \ub1 10.3 years), 14 NIDDM patients (9 male, 5 female; 47.0 \ub1 7.5 years) and 12 healthy subjects (7 male, 5 female; 41.5 \ub1 6.3 years) as a control (C) group. The duration of diabetes (DD) and glycosylated hemoglobin (HbA1c) levels were significantly higher in the IDDM patients. The ventricular ejection fraction and peak ejection rate (PER) were assessed by gated radionuclide left ventriculography and were similar in three groups, while the peak filling rate (PFR) was lower in the NIDDM patients compared to the IDDM patients (p < 0.05) and controlled healthy subjects (p < 0.01, IDDM = 3.39 \ub1 1.14; NIDDM = 2.65 \ub1 0.83; C = 3.55 \ub1 0.73), the time to PFR was significantly more prolonged in the NIDDM group than in the IDDM (p < 0.05) and C groups (p < 0.05, NIDDM = 162 \ub1 26; IDDM = 140 \ub1 28; C = 142 \ub1 23). The PFR/PER ratio was near the normal value (-1) in the IDDM patients and controlled subjects, while in the NIDDM patients it was reduced (= 0.84 \ub1 0.18). Seven IDDM and 4 NIDDM patients had borderline signs of cardiovascular autonomic neuropathy, unrelated to DD, HbAic and scintigraphic parameters. Left ventricular systolic performance was substantially normal and similar in both the IDDM and NIDDM patients. Ventricular diastolic filling was impaired in the NIDDM patients, as shown by the decrease in PFR and in particular in the PFR/PER ratio. Our radionuclide data suggest that the NIDDM patients had a prevalent abnormality of ventricular diastolic performance, with respect to the IDDM patients, although the latter patients had higher DD and HbA1cvalues