New molecular targets for the treatment of sarcoidosis

Abstract

Purpose of review Sarcoidosis is a chronic granulomatous disease typically affecting the lung, lymph nodes, and other organ systems. Evidence suggests that the morbidity and mortality rates for sarcoidosis in the USA are rising, despite widespread use of anti-inflammatory therapies. In this review, we survey new therapies that target specific inflammatory pathways in other diseases (such as rheumatoid arthritis, Crohn’s disease, and psoriasis) that are similar to pathways relevant to sarcoidosis immunopathogenesis, and therefore, represent potentially new sarcoidosis therapies. Recent findings Immunopathogenesis of sarcoidosis has been well elucidated over the past few years. There is abundant evidence for T-cell activation in sarcoidosis leading to activation of both Th1 and Th17 inflammatory cascades. Therapies targeting T-cell activation, Th1 pathways (such as the interleukin-6 inhibitors), Th17 pathway mediators, and others have been Food and Drug Administration approved or under investigation to treat a variety of autoimmune inflammatory diseases, but have not been studied in sarcoidosis. Targeting the p38 mitogen-activated protein kinases and the ubiquitine proteasome system with new agents may also represent a novel therapeutic option for patients with sarcoidosis. Summary Rising morbidity and mortality rates for patients with sarcoidosis strongly support the need to develop more effective anti-inflammatory therapies to treat chronic disease.

Sarcoidosis and autoimmune hemolytic anemia: is there a pathogenic link?

“…The interaction leads to the activation of an inflammatory response through a Th1 cells, the recruitment of inflammatory cells and the formation of non caseating granulomas. More recently, there is a compelling evidence for a role of Th17 immune pathways in the generation and maintenance of sarcoidosis granulomas (15).AIHA pathogenesis begins with the presence of immunoglobulin G antibodies reacting with protein antigens on the surface of red blood cells at normal body temperature mediated by Th1 bias (10,16). So, Th1 cells are responsible for the initial autoantibody response and that the Th17 cells drive the chronic inflammation in autoimmune conditions including sarcoidosis and AIHA.…”

Cutaneous Sarcoidosis

“…64 Newer agents such as Janus kinase (JAK) inhibitors, IL-12/-23 inhibitors, and IL-17 inhibitors are under consideration or study for sarcoidosis based on cytokine studies of sarcoidal tissue. [95][96][97] IL-12/-23 inhibitors have been studied in a randomized control trial and failed to show efficacy. IL-17 inhibitors have been reported to induce granulomatous inflammation in early reports.…”

Sarcoidosis as an Autoimmune Disease

“…There are studies on the possible beneficial effect of using IL-6 suppressors. The level of this cytokine is increased in patients with sarcoidosis and correlates with the level of CD3+ lymphocytes (tocilizumab), cytotoxic Tlymphocyte (abetacept), and IL-12/IL-23P40 and Th17 pathways, inducing the production of TNFα (ustekinumab, tildrakizumab, secukinumab) (18). The effectiveness of immunosuppressive therapy in the treatment of patients with sarcoidosis alludes to the important role of the autoimmune component in the pathogenesis of this disease.…”