Sjogren's syndrome: Autoimmune epithelitis

Sjogren's syndrome (SS), the ideal model to study autoimmunity and lymphoid malignancy, is a common chronic disease which in the last 30 years has been studied extensively on clinical and pathophysiological grounds. Clinical studies regarding kidney disease in SS patients have shown that the predominate lesion is interstitial nephritis which produces tubular dysfunction. Studies on lung involvement have previously indicated that one-fourth of SS patients suffer from subclinical, interstitial lung disease. Reevaluation, however, of the pulmonary disease, using functional, radiologic (including CT-scan), and histopathologic studies, revealed that the lesion starts peribronchially. Finally, evaluation of liver disease in SS patients revealed that this consists of a pericholangeal round-cell infiltrate resembling the early lesion of primary biliary cirrhosis. These clinical studies suggest that the majority of extraglandular manifestations of SS are due to the attraction of lymphocytes by different epithelial tissues. Studies of the epithelial cells of minor salivary glands from SS patients have shown that these inappropriately and selectively express HLA class II molecules and the protooncogene c-myc. Evaluation of cytokines in the minor salivary glands from these patients, by in situ hybridization, revealed that the mRNA of the proinflammatory cytokines IL-1 and IL-6 also comes from the epithelial cells. Finally, proviral DNA is incorporated in the DNA of epithelial cells. On the basis of these clinical and basic observations, we suggest that the major suffering cell in SS patients is the epithelium and thus we propose this descriptive term 'autoimmune epithelitis' instead of 'Sjogren's syndrome'

A recommended paradigm for vaccination of rheumatic disease patients with the SARS-CoV-2 vaccine

Autoimmune and autoinflammatory rheumatic disorders (ARD) are treated with antimetabolites, calcineurin inhibitors and biologic agents either neutralizing cytokines [Tumor Necrosis Factor (TNF), Interleukin (IL)-1, IL-6, IL-17, B-cell activating factor] or being directed against B-cells (anti-CD-20), costimulatory molecules or JAK kinases. Similarly for the influenza or pneumococcal vaccines, there is limited data on the effectiveness of vaccination against SARS-CoV-2 infection and COVID-19 prevention for this susceptible patient population. Moreover, preliminary data from vaccinated organ transplanted, inflammatory bowel and connective tissue disease patients suggests only limited immunogenicity after the first vaccine dose, particularly in patients on immunosuppressive regimens. Herein a set of recommendations for the vaccination of immune suppressed patients with the SARS-CoV-2 vaccines is proposed aimed at achieving optimal vaccine benefit without interfering with disease activity status. Moreover, rare autoimmune adverse events related to vaccinations are discussed. © 2021 Elsevier Lt

Sjögren's syndrome: A forty-year scientific journey

My long scientific journey studying as a disease model Sjogren's syndrome (SS) gave me the opportunity to uncover the mysteries of systemic autoimmune diseases. After an extensive training, under the supervision of the major autoimmune disease investigators, I was able to convey and expand the acquired knowledge through inspiring my students and collaborators. Our research enriches the understanding of the wide clinical spectrum of the syndrome and the clinical, laboratory and molecular events predicting or being responsible for lymphomagenesis. Our molecular and cellular studies indicated that the target of autoimmunity in SS, the activated glandular epithelial cells, play significant role in the initiation and perpetuation of the autoimmune process. Furthermore, discovery of the epitopes on autoantigens where the autoimmune humoral reactivity is directed against, provided us tools to develop specific and sensitive diagnostic assays, to unmask similarities of the epitope sequence with infectious agents and gave us the potential to use them as therapeutic modalities. © 2014 Elsevier Ltd

Foxp3+ T-regulatory cells in Sjögren's syndrome: Correlation with the grade of the autoimmune lesion and certain adverse prognostic factors

Sjögren's syndrome (SS) is a chronic autoimmune exocrinopathy associated with variable lymphocytic infiltration of the affected organs (primarily salivary and lacrimal glands) and broad clinical manifestations, including lymphoma development. To investigate the potential implication of Foxp3+ T-regulatory cells in the regulation of SS inflammatory responses, we studied their incidence in the minor salivary glands (MSGs) and their relationship with histopathological and clinical disease parameters. Similar percentages of infiltrating Foxp3+ cells were observed in the MSG lesions of all SS patients (n = 30) and non-SS sialadenitis controls (n = 7). Foxp3+ cells were not detected in sicca-complaining controls with negative biopsy (n = 6). In SS patients, Foxp3+ cell frequency varied according to lesion severity, with the highest and lowest frequencies obtained in intermediate and mild MSG lesions, respectively. In the peripheral blood of these patients, reverse distribution of Foxp3+ cells was observed. Furthermore, the frequency of Foxp3+ cells in the MSG lesions and peripheral blood was negatively associated (r = -0.6679, P = 0.0065). MSG-infiltrating Foxp3+ cells were found to positively correlate with biopsy focus score (P = 0.05), infiltrating mononuclear cells, dendritic cells, and macrophages (P ≤ 0.024 each), and serum C4 levels (P = 0.0328), whereas lower Foxp3+ cell incidence correlated with adverse predictors for lymphoma development, such as the presence of C4 hypocomplementemia (P = 0.012) and SG enlargement (tendency, P = 0.067). Our findings suggest that the Foxp3+ T-regulatory cell frequency in the MSG lesions of SS patients correlates with inflammation grade and certain risk factors for lymphoma development. Copyright © American Society for Investigative Pathology

Salivary gland imaging techniques for the diagnosis of Sjögren's syndrome

Extensive evaluation of the utility of newer imaging techniques in diagnosing Sjögren's syndrome has revealed that all of the techniques provide useful information that can help to differentiate between patients with Sjögren's syndrome and healthy individuals, with sensitivity and specificity ranging from 70-95%. However, there is a need for greater technique validation using disease-control patients with dry mouth and careful comparison with other diagnostic methods. Furthermore, a universally accepted grading of abnormal imaging findings observed in salivary glands is needed. Clarification of these matters will enable the clinician to choose the most reliable imaging technique to diagnose Sjögren's syndrome. © 2009 Future Medicine Ltd

A case of antisynthetase syndrome

Respiratory complaints alone or in association with musculoskeletal complaints can be the predominant presenting feature of antisynthetase syndrome. Therefore, antibodies to cellular antigens should be evaluated in such clinical settings. © 2020 The Authors. Clinical Case Reports published by John Wiley & Sons Lt