Biologic Treatments in Interstitial Lung Diseases

Interstitial lung diseases (ILD) represent a group of heterogeneous parenchymal lung disorders with complex pathophysiology, characterized by different clinical and radiological patterns, ultimately leading to pulmonary fibrosis. A considerable proportion of these disease entities present with no effective treatment, as current therapeutic regimens only slow down disease progression, thus leaving patients, at best case, with considerable functional disability. Biologic therapies have emerged and are being investigated in patients with different forms of ILD. Unfortunately, their safety profile has raised many concerns, as evidence shows that they might cause or exacerbate ILD status in a subgroup of patients. This review article aims to summarize the current state of knowledge on their role in patients with ILD and highlight future perspectives

Spleen Tyrosine Kinase (Syk) Regulates Systemic Lupus Erythematosus (SLE) T Cell Signaling

Engagement of the CD3/T cell receptor complex in systemic lupus erythematosus (SLE) T cells involves Syk rather than the zeta-associated protein. Because Syk is being considered as a therapeutic target we asked whether Syk is central to the multiple aberrantly modulated molecules in SLE T cells. Using a gene expression array, we demonstrate that forced expression of Syk in normal T cells reproduces most of the aberrantly expressed molecules whereas silencing of Syk in SLE T cells normalizes the expression of most abnormally expressed molecules. Protein along with gene expression modulation for select molecules was confirmed. Specifically, levels of cytokine IL-21, cell surface receptor CD44, and intracellular molecules PP2A and OAS2 increased following Syk overexpression in normal T cells and decreased after Syk silencing in SLE T cells. Our results demonstrate that levels of Syk affect the expression of a number of enzymes, cytokines and receptors that play a key role in the development of disease pathogenesis in SLE and provide support for therapeutic targeting in SLE patients

Experience with rituximab in scleroderma: results from a 1-year, proof-of-principle study

Objective. To assess the efficacy of rituximab (RTX) in SSc

What's New in the Treatment of Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a chronic autoimmune multisystem disease with a variable presentation and manifestations ranging from mild to severe or even life-threatening. There is an ongoing and unmet need for novel, disease-specific, effective and safe treatment modalities. The aim of this review is to summarize data on SLE treatment that have emerged over the last 3 years. We will put emphasis on studies evaluating potential treatments on severe lupus manifestations such as lupus nephritis. Despite the existence of several therapeutic agents in SLE, the disease keeps causing significant morbidity. It is encouraging that a variety of therapeutic options are currently under investigation, although there are occasional trial failures.</jats:p

The Role of B Cells in Scleroderma Lung Disease Pathogenesis

Systemic sclerosis (SSc) is a chronic, autoimmune, multisystem disease characterized by tissue fibrosis that, apart from the skin, may affect the lungs among other organs. B cells have been found in tissue lymphocytic infiltrates; in the lungs are encountered in lymphoid aggregates. The abnormal and hyperreactive B cell in SSc may initiate and perpetuate the fibrotic process via incompletely understood mechanisms. Studies in animal models of SSc have demonstrated that B cell dysregulation is an early event in disease pathogenesis. Functional disturbances of BCR signaling such as decreased inhibitory CD22 signal transduction or augmented CD19-mediated signaling result in prolonged B cell activation. Antagonism of BAFF, a cytokine known for his central role in B cell survival and maturation, not only suppresses the production of fibrogenic cytokines such as IL-6 and IL-10, but also amplifies antifibrogenic cytokine secretion such as IFN-γ and it finally contributes to skin fibrosis attenuation. B cells subsets in SSc patients display several abnormalities. Naïve B cells are increased, in contrast to switched memory B cells that are not only decreased but also activated. Disturbances in the expression of molecules that are involved in B cell tuning have also been described. Interestingly, a distinct B cell population characterized by anergy and exhaustion has been found to be increased in patients with SSc-ILD. Another B cell subset, the CD30+GM-Beff, is capable to differentiate monocytes to dendritic cells and is increased in SSc patients with ILD. Of note, patients with SSc-ILD exhibit increased expression of the inhibitory receptor FcγRIIB on naïve and double negative B cells aiming perhaps to counterbalance the abnormal B cell activation. Studies of B cell targeted treatments have demonstrated promising clinical efficacy. Therefore, B cell eliminating therapies could be integrated into the therapeutic armamentarium of patients suffering from SSc-ILD aiming to at least stabilize the fibrotic lung process.</jats:p