Immunogenetics of Systemic Sclerosis.

Systemic sclerosis (SSc) is a rare autoimmune connective tissue disorder characterized by massive fibrosis, vascular damage, and immune imbalance. Advances in rheumatology and immunology over the past two decades have led to a redefinition of systemic sclerosis, shifting from its initial perception as primarily a "hyperfibrotic" state towards a recognition of systemic sclerosis as an immune-mediated disease. Consequently, the search for genetic markers has transitioned from focusing on fibrotic mechanisms to exploring immune regulatory pathways. Immunogenetics, an emerging field at the intersection of immunology, molecular biology, and genetics has provided valuable insights into inherited factors that influence immunity. Data from genetic studies conducted thus far indicate that alterations in genetic messages can significantly impact disease risk and progression. While certain genetic variations may confer protective effects, others may exacerbate disease susceptibility. This paper presents a comprehensive review of the most relevant genetic changes that influence both the risk and course of systemic sclerosis. Special emphasis is placed on factors regulating the immune response, recognizing their pivotal role in the pathogenesis of the disease.

Novel Therapeutic Strategies in the Treatment of Systemic Sclerosis.

Systemic sclerosis is a connective tissue disease of unknown origin and with an unpredictable course, with both cutaneous and internal organ manifestations. Despite the enormous progress in rheumatology and clinical immunology, the background of this disease is largely unknown, and no specific therapy exists. The therapeutic approach aims to treat and preserve the function of internal organs, and this approach is commonly referred to as organ-based treatment. However, in modern times, data from other branches of medicine may offer insight into how to treat disease-related complications, making it possible to find new drugs to treat this disease. In this review, we present therapeutic options aiming to stop the progression of fibrotic processes, restore the aberrant immune response, stop improper signalling from proinflammatory cytokines, and halt the production of disease-related autoantibodies.

Jak Inhibitors for Treatment of Autoimmune Diseases: Lessons from Systemic Sclerosis and Systemic Lupus Erythematosus.

Systemic sclerosis and systemic lupus erythematosus represent two distinct autoimmune diseases belonging to the group of connective tissue disorders. Despite the great progress in the basic science, this progress has not been translated to the development of novel therapeutic approaches that can radically change the face of these diseases. The discovery of JAK kinases, which are tyrosine kinases coupled with cytokine receptors, may open a new chapter in the treatment of so far untreatable diseases. Small synthetic compounds that can block Janus kinases and interact directly with cytokine signalling may provide therapeutic potential in these diseases. In this review, we discuss the therapeutic potential of Jak kinases in light of the cytokine network that JAK kinases are able to interact with. We also provide the theoretical background for the rationale of blocking cytokines with specific JAK inhibitors.