Emerging treatment for Sjögren's disease: a review of recent phase II and III trials.

Introduction: Sjögren's Disease, SjD, is a systemic autoimmune disorder characterized by reduced function of the salivary and lacrimal glands. Patients suffer from dryness, fatigue, and pain and may present with or without extra-glandular organ involvement. Symptoms limit SjD patients' quality of life and are the most difficult to improve with therapy.

Treatment of Sjögren's syndrome: current therapy and future directions.

SS is usually described as having severe fatigue, dryness, diffuse pain, glandular swelling, and various extraglandular (systemic) manifestations. Clinical trials have generally failed because the vast majority of enrolled patients had no extraglandular manifestations at the time of enrolment but suffered from fatigue, dryness and pain that did not significantly respond to the study medication. A number of hypotheses on the pathogenesis of pSS have been put forward, including disturbances of innate and adaptive immunity as well as abnormalities of the interface between immune disorders and the neuro-endocrine system related to lacrimal and secretory gland dysfunction.

Sjögren Syndrome: Why Do Clinical Trials Fail?

Sjögren syndrome (SS) comprises glandular and extraglandular manifestations. Double-blind prospective trials of traditional disease-modifying antirheumatic drugs and biologics have failed because they have not improved benign symptoms, the major cause of lowered quality of life. Rituximab has proven effective in SS patients with associated mixed cryoglobulinemia, parotid gland swelling, lymphocytic interstitial pneumonitis, thrombocytopenia, and other manifestations.

Broadly neutralizing antibodies protect against hepatitis C virus quasispecies challenge.

A major problem in hepatitis C virus (HCV) immunotherapy or vaccine design is the extreme variability of the virus. We identified human monoclonal antibodies (mAbs) that neutralize genetically diverse HCV isolates and protect against heterologous HCV quasispecies challenge in a human liver-chimeric mouse model. The results provide evidence that broadly neutralizing antibodies to HCV protect against heterologous viral infection and suggest that a prophylactic vaccine against HCV may be achievable.

Sjögren's syndrome in dermatology.

Sjogren's Syndrome (SS) is a systemic autoimmune disease characterized by dry eyes (keratoconjunctivis sicca) and dry mouth (xerostomia). To fulfill diagnostic criteria, patients must have objective signs of dryness on examination and laboratory confirmation of an autoimmune process as evidenced by a positive autoantibody to SS-A antigen or a characteristic lip biopsy. SS may exist as a primary condition or in association with other systemic autoimmune disorders (termed secondary SS) such as rheumatoid arthritis, systemic lupus erythematous (SLE), progressive systemic sclerosis (scleroderma), or dermatomyositis.

Sjögren's syndrome.

Sjögren's syndrome is a chronic autoimmune disorder of the exocrine glands with associated lymphocytic infiltrates of the affected glands. Dryness of the mouth and eyes results from involvement of the salivary and lacrimal glands. The accessibility of these glands to biopsy enables study of the molecular biology of a tissue-specific autoimmune process.

Molecular analysis of the human autoantibody response to alpha-fodrin in Sjögren's syndrome reveals novel apoptosis-induced specificity.

Lymphocyte infiltration of salivary and lacrimal glands leading to diminished secretion and gland destruction as a result of apoptosis is thought to be pivotal in the pathogenesis of Sjögren's syndrome (SS). The cytoskeletal protein alpha-fodrin is cleaved during this apoptotic process, and a strong antibody (Ab) response is elicited to a 120-kd fragment of cleaved alpha-fodrin in the majority of SS patients, but generally not in other diseases in which apoptosis also occurs. Little is known about the anti-alpha-fodrin autoantibody response on a molecular level.

Sjogren's syndrome: evolving therapies.

Sjogren's syndrome (keratoconjunctivis sicca) is a relatively common disorder with incidence of approximately 0.5% of adult women. It has both local (ocular and oral) features as well as systemic manifestations.

Sjögren's syndrome: mechanisms of pathogenesis involve interaction of immune and neurosecretory systems.

Although biopsies of salivary and lacrimal glands from patients with Sjögren's syndrome (SS) have focal lymphocytic infiltrates and partial destruction of glandular secretory units (acinar and ductal structures), the degree of dryness is beyond that expected for the level of glandular destruction. The failure to exhibit adequate secretory function is not due simply to the destruction of neural innervation to the residual glandular elements or the absence of receptors for acetylcholine on the glandular cells. It is likely that release of cytokines by lymphocytes and glandular cells (especially interleukin-1, interleukin-6 and tumor necrosis factor alpha), autoantibodies and metalloproteinases lead to decreased release of neurotransmitters and decreased response of the residual glandular cells to available neurotransmitters.