Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disorder characterized by chronic inflammation of exocrine glands leading to tissue damage and progressive secretory impairment that seriously affect the quality of life. Recent advances in the understanding of pSS pathogenic mechanisms, as well as the introduction of biologic treatments that selectively target cellular and soluble mediators of inflammatory/autoimmune response, led to major changes in the management of pSS. A large body of evidence has been pointing to a central role of B cells in the development, maintenance, and progression of the disease, with multiple roles at different points of pSS pathophysiology. Excessive B-cell activation is responsible for a number of extra-glandular manifestations and serological features of pSS. These include hypergammaglobulinemia, cryoglobulinemia elevated levels of free light chains and ß2-microglobulin, presence of anti-Sjögren’s-syndrome-related antigen A (anti-SSA)/Ro and anti-Sjögren’s syndrome type B (SSB) /La autoantibodies, RF, hypocomplementemia, hypergammaglobulinemic purpura, arthritis, vasculitis, neuropathy, and glomerulonephritis. Finally, prolonged B-cell survival and aberrant B-cell activity may lead to the development of non-Hodgkin lymphoma (NHL) in 5% of pSS patients.
However, in the previous years, the rationale for using immunosuppressive and biologic agents in pSS is mainly based on their efficacy in other autoimmune disorders, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), expert opinion, and uncontrolled studies. The recent release of the first set of evidence-based recommendations for the management of pSS has filled a longstanding gap for the majority of drugs commonly used in the spectrum of extra-glandular involvement.
The contributions to this topic should cover all aspects of pSS management and will provide an overview of the advantages and limitations of different compounds explored so far along with reflection on possible new therapeutic approaches.
Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disorder characterized by chronic inflammation of exocrine glands leading to tissue damage and progressive secretory impairment that seriously affect the quality of life. Recent advances in the understanding of pSS pathogenic mechanisms, as well as the introduction of biologic treatments that selectively target cellular and soluble mediators of inflammatory/autoimmune response, led to major changes in the management of pSS. A large body of evidence has been pointing to a central role of B cells in the development, maintenance, and progression of the disease, with multiple roles at different points of pSS pathophysiology. Excessive B-cell activation is responsible for a number of extra-glandular manifestations and serological features of pSS. These include hypergammaglobulinemia, cryoglobulinemia elevated levels of free light chains and ß2-microglobulin, presence of anti-Sjögren’s-syndrome-related antigen A (anti-SSA)/Ro and anti-Sjögren’s syndrome type B (SSB) /La autoantibodies, RF, hypocomplementemia, hypergammaglobulinemic purpura, arthritis, vasculitis, neuropathy, and glomerulonephritis. Finally, prolonged B-cell survival and aberrant B-cell activity may lead to the development of non-Hodgkin lymphoma (NHL) in 5% of pSS patients.
However, in the previous years, the rationale for using immunosuppressive and biologic agents in pSS is mainly based on their efficacy in other autoimmune disorders, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), expert opinion, and uncontrolled studies. The recent release of the first set of evidence-based recommendations for the management of pSS has filled a longstanding gap for the majority of drugs commonly used in the spectrum of extra-glandular involvement.
The contributions to this topic should cover all aspects of pSS management and will provide an overview of the advantages and limitations of different compounds explored so far along with reflection on possible new therapeutic approaches.
