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Abstract Sjögren's syndrome (SS) is a chronic autoimmune disease that primarily affects the exocrine glands, resulting in their functional impairment. In SS, lymphocytic infiltration of salivary and lacrimal glands, and deposition of several types of autoantibodies, mainly anti-SS-A (anti-Ro) and anti-SS-B (anti-La), lead to chronic inflammation, with xerostomia and keratoconjunctivitis sicca. In its primary form (pSS), SS does not involve additional connective tissue diseases, whereas in its secondary and more common form (sSS), SS presents in association with other rheumatic autoimmune diseases, mainly rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). As in most autoimmune diseases, environmental, hormonal and genetic factors are implicated in SS pathogenesis. In SS T cells predominate in mild lesions, whereas B cells predominate in advanced lesions. Th1, Th2, Th17, follicular helper T (Tfh) cells and regulatory cells (Tregs/Bregs), with their characteristic cytokine profiles, have been implicated in the pathogenesis of SS. It has been suggested that Th1 and Th17 cells initiate SS and, as the disease progresses, Th2 and Tfh cells predominate. It is assumed that, as in all autoimmune and inflammatory conditions, tolerance defects contribute to SS pathogenesis. It is intriguing that in SS it remains unclear which types of regulatory cells are functional and whether they ameliorate or worsen the disease. In this review we present a comprehensive update on SS with emphasis on immune system involvement, and suggest new insights into SS immunopathogenesis. Highlights • Sjögren's syndrome (SS) is frequently associated with other autoimmune diseases. • Ro60 antibodies, salivary gland and lip biopsies are most specific diagnostic tests. • HLA-DQ haplotypes present the strongest genetic risk factors for primary SS. • T cells predominate in mild lesions, B cells predominate in advanced lesions. • Loss of tolerance in SS is not accompanied by loss of Treg/Breg function. • Causality for BAFF and TGF-β in SS points to potential for immunologic therapies. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) that affects nearly 2.8 million people each year. MS distinguishes three main types: relapsing-remitting MS (RRMS), secondary progressive MS (SPMS) and primary progressive MS (PPMS). RRMS is the most common type, with the majority of patients eventually progressing to SPMS, in which neurological development is constant, whereas PPMS is characterized by a progressive course from disease onset. New or additional insights into the role of effector and regulatory cells of the immune and CNS systems, Epstein-Barr virus (EBV) infection, and the microbiome in the pathophysiology of MS have emerged, which may lead to the development of more targeted therapies that can halt or reverse neurodegeneration. Depending on the type and severity of the disease, various disease-modifying therapies (DMTs) are currently used for RRMS/SPMS and PPMS. As a last resort, and especially in highly active RRMS that does not respond to DMTs, autologous hematopoietic stem cell transplantation (AHSCT) is performed and has shown good results in reducing neuroinflammation. Nevertheless, the question of its potential role in preventing disability progression remains open. The aim of this review is to provide a comprehensive update on MS pathophysiology, assessment of MS disability progression and current treatments, and to examine the potential role of AHSCT in preventing disability progression. • New insights into MS pathophysiology hold promise for improving MS treatment. • DMT options for MS treatment continue to expand. • So far, no DMT has proven useful in halting MS disability progression. • AHSCT appears to be a promising alternative, especially in very aggressive RRMS. • AHSCT may play a role in halting progression of MS disability in carefully selected patients. [ABSTRACT FROM AUTHOR]