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T Cells in the Pathogenesis of Sjögren’s Syndrome: More Than Just Th1 and Th2

1 Introduction In the last few decades, T lymphocytes have been widely investigated in the pathogenic scenario of autoimmune diseases. To date, a consistent body of evidence points out the key role of this arm of the immune system in the induction and perpetuation of primary Sjögren’s syndrome (SS). The first milestone in this field is the study by Fox et al. who reported in 1983 that…

Glandular Epithelium: Innocent Bystander or Leading Actor?

1 Introduction Sjögren’s syndrome (SS) is an autoimmune disease with heterogeneous clinical pictures, which extend from benign local exocrinopathy that affects primarily the salivary and lachrymal glands to systemic disorder, and in approximately 5% of patients evolves to B-cell malignancies. Furthermore, SS can be expressed as an isolated clinical entity or coexpressed with virtually every other systemic autoimmune rheumatic disorder. Most of these features are present…

Histology of Sjögren’s Syndrome

1 Introduction The formation of periductal lymphocytic infiltrates within the inflamed salivary glands represents the histological hallmark of primary Sjögren’s syndrome (pSS). Lymphomonocytic aggregates can spread within the tissue, affecting salivary gland morphology and function. On a discrete percentage of patients (∼25%), it is possible to observe the formation of organized germinal center (GC)-like structure, detection of which has been correlated to lymphoma development. Salivary gland…

Sjögren’s Syndrome and Environmental Factors

1 Introduction Sjögren’s syndrome (SS) is a systemic, chronic, autoimmune, inflammatory condition involving the exocrine glands. First defined as “autoimmune epithelitis” by Moutsopoulos, SS is characterized by the presence of lymphocyte infiltrates in glandular tissue that might lead, over time, to a progressive glandular dysfunction. The type I interferon (IFN) pathway is highly expressed and there is evidence of the so-called “IFN signature” in peripheral blood…

Autoantigens and Autoantibodies in the Pathogenesis of Sjögren’s Syndrome

1 Introduction It is well established that environmental factors in concert with an appropriate genetic background play a fundamental role in triggering Sjögren’s syndrome (SS) leading to chronic inflammation of the target organs through different mechanisms, among which the molecular mimicry between infectious agents and autoantigens has been the most studied. An aberrant autoimmune response due to T- and B-lymphocyte hyperactivity and autoantibody production is known…

Genetics, Genomics, Gene Expression Profiling, and Epigenetics in Sjögren’s Syndrome

Acknowledgments In the past year Professor Simon Bowman has consulted for Eli Lilly, Takeda Pharmaceuticals, UCB, Novartis, Glenmark, Celgene, Medimmune, GSK, and Ono, and is in receipt of an Arthritis Research UK grant to which Roche Pharmaceuticals is contributing rituximab without charge. Dr. Ben Fisher has consulted for Medimmune, Takeda, and Novartis. 1 Historical Background Henrik Sjögren, a Swedish ophthalmologist, described the condition that bears his…

Spontaneous and Inducible Animal Models of Sjögren’s Syndrome

1 Spontaneous Models Most of the information from animal models of (Sjögren’s syndrome) SS derives from studies of inbred mouse strains or mice carrying specific genetic defects that spontaneously develop autoimmune sialadenitis. These included New Zealand black (NZB), NZB/New Zealand white (NZW), and the Murphy Roths large (MRL) with its substrains. In these models, SS-like pathology is mostly associated with other autoimmune phenomena typical of systemic…

Sjögren’s Syndrome–Associated Lymphoma

1 Introduction Sjögren’s syndrome (SS) is an autoimmune systemic disease associated with B-cell lymphoproliferation and an increased risk of B-cell non-Hodgkin lymphoma (NHL) development compared with the general population. NHLs are a highly heterogeneous group of malignancies that originate in lymphatic hematopoietic tissue, classified into B-cell and T-cell lymphomas, which account for about 90% and 10% of lymphomas respectively. The distinct subtypes of NHL show significant…

Imaging Procedures Useful for the Diagnosis of Sjögren’s Syndrome: Abnormalities of the Major Salivary Glands

Primary Sjögren’s syndrome (pSS) is an autoimmune disease affecting predominantly the salivary glands. Most of the classification criteria have considered involvement of salivary glands as a major sign of the disease. This involvement can be assessed by imaging procedures such as sialography or scialoscintigraphy (considered in the classification criteria currently used), which were the most commonly used procedures until 1990. More recently the development of magnetic…

Classification Criteria for Sjögren’s Syndrome

1 General Concepts on Classification Criteria Sjögren’s syndrome (SS) is a systemic autoimmune disease (SAD) that primarily affects the exocrine glands, predominantly the salivary and lachrymal glands, and leads to their functional impairment with consequent persistent dryness of the eye and mouth. The pathological hallmark of the disorder is a focal lympho-monocytic infiltration of the target tissue. In addition to the disease-specific exocrine manifestations, SS is…

Management of Sjögren’s Syndrome

1 Introduction Sjögren’s syndrome (SS) is a chronic autoimmune exocrinopathy affecting predominantly middle-aged women and displaying lymphocytic infiltration and secretory dysfunction of the exocrine glands (primarily the salivary and lacrimal glands, resulting in oral and ocular dryness). Depending on the absence or presence of other connective tissue disorders, SS can be classified into primary SS and SS associated with other systemic autoimmune disorders, respectively. Though classically…

Clinical Features

1 Introduction The clear identification of primary Sjögren’s syndrome (pSS) as a systemic disease occurred only in the 1980s and 1990s. Indeed, in the early 1970s, the only characterized systemic manifestations were bronchitis sicca, interstitial nephritis, and the risk of developing lymphoma in the same patients. Later on, some nonspecific manifestations, including Raynaud phenomenon and arthralgias, were described, and in the early 1980s, clinical and immunopathological…

Introduction: History of Sjögren’s Syndrome

1 Introduction Sjögren’s syndrome (SS) is a complex disorder characterized by both organ-specific and systemic manifestations, potentially expanding to lymphoproliferative complications. In addition to occurring as a primary or secondary disease, SS can occur in association with organ-specific autoimmune diseases, as well as in overlapping complex entities with the major connective tissue diseases. SS is named after the Swedish ophthalmologist Henrik Sjögren, who presented his doctoral…

Classification and Health Impact of the Rheumatic Diseases

When you are frustrated with me because of things I cannot do, just think how frustrated I must be because I am not able. –One or more of the 91 million people in the United States with a musculoskeletal disorder Key Points Approximately 33% of the US population has arthritis and/or back pain. One out of every five office visits to a primary care provider and…

Classification and Diagnostic Criteria

The unique role of criteria sets for classification and diagnosis in rheumatology reflects the clinical and scientific challenges characteristic of rheumatic diseases. Rheumatic diseases often cannot be defined by a single clinical, laboratory, radiologic, or pathologic feature because of their complicated and heterogeneous nature. Consequently, in the absence of a “gold standard” test, most rheumatic disorders are diagnosed or classified depending on a combination of findings.…

Bone tumors

Key Points ■ Bone tumors present with pain, swelling, pathologic fracture, or loss of use or as an incidental finding. ■ Urgent investigations of plain radiography, magnetic resonance imaging, or computed tomography are required with formal diagnostic core biopsy. ■ Older adults (older than 60 years of age) with a new symptomatic bone lesion should be considered to have either metastatic carcinoma or multiple myeloma until…

Hypermobility syndrome

Key Points ■ Joint hypermobility as a clinical entity is difficult to define given current parameters; the Beighton score is not fit for this purpose, and a new measurement tool is required to identify patients with significant global joint laxity. ■ Diagnostic criteria have changed. The 2017 International Diagnostic Criteria for Ehlers-Danlos Syndrome (EDS) has given more clarity to the various EDS types. The term benign…

Heritable connective tissue disorders

Key Points ■ Heritable disorders of the skeleton and connective tissues are individually rare but collectively constitute an important source of morbidity and mortality. ■ Improved diagnostic classification criteria allow more accurate prognostication for disorders such as Marfan syndrome, Ehlers-Danlos syndrome, and osteopetrosis. ■ Over the past 40 years, the individual genes causing most of these disorders have been identified, paving the way for accurate molecular…