The evaluation of cytokines to help establish diagnosis and guide treatment of autoinflammatory and autoimmune diseases

Abstract

Our knowledge of the role of cytokines in pathologic conditions has increased considerably with the emergence of molecular and genetic studies, particularly in the case of autoinflammatory monogenic diseases. Many rare disorders, considered orphan until recently, are directly related to abnormal gene regulation, and the treatment with biologic agents (biologics) targeting cytokine receptors, intracellular signaling or specific cytokines improve the symptoms of an increasing number of chronic inflammatory diseases. As it is currently impossible to systematically conduct genetic studies for all patients with autoinflammatory and autoimmune diseases, the evaluation of cytokines can be seen as a simple, less time consuming, and less expensive alternative. This approach could be especially useful when the diagnosis of syndromes of diseases of unknown etiology remains problematic. The evaluation of cytokines could also help avoid the current trial-and-error approach, which has the disadvantages of exposing patients to ineffective drugs with possible unnecessary side effects and permanent organ damages. In this review, we discuss the various possibilities, as well as the limitations of evaluating the cytokine profiles of patients suffering from autoinflammatory and autoimmune diseases, with methods such as direct detection of cytokines in the plasma/serum or following ex vivo stimulation of PBMCs leading to the production of their cytokine secretome. The patients' secretome, combined with biomarkers ranging from genetic and epigenetic analyses to immunologic biomarkers, may help not only the diagnosis but also guide the choice of biologics for more efficient and rapid treatments.

Inflammatory Biomarkers in Postural Orthostatic Tachycardia Syndrome with Elevated G-Protein-Coupled Receptor Autoantibodies

“…Our patients demonstrated elevations of five biomarkers of inflammation (IL-1β, IL-21, TNFα, INFγ, and CD30) that are known to be elevated in autoimmune disorders such as RA and SLE [64]. The development of autoantibodies in POTS could potentially be due to a dysregulation of an interleukin, such as is seen in the pathogenesis of SLE with elevations of IL-21, TNF, and INFγ, as observed in our patients [65].…”

Future of preventing and managing common chronic inflammatory diseases

“…Substantial new understanding about autoinflammatory and autoimmune diseases has emerged due in large part to classification of such diseases as a biologic continuum (Figure 1). 27,28 …”

“…An example of a rare monogenic autoimmune disease is ALPS (autoimmune lymphoproliferative syndrome). Reprinted with permission from Journal of Leukocyte Biology 28 …”

Multiple Cytokines Elevated in Patients with Keloids: Is It an Indication of Auto-Inflammatory Disease?

“…Auto-inflammatory diseases result from abnormal innate immune system, characterized by elevated inflammatory cytokines. 16 , 17 Pharmacological interactions with cytokines either at the production or receptor levels have resulted in promising outcomes in some of these diseases. 18 The majority of studies done to demonstrate cytokines levels in patients with keloids have largely been in vitro or limited to small sample sizes which makes it difficult to conclude whether keloids could fit into this group of disorders.…”

“…Probably the most studied among these as far as keloid pathogenesis is concerned is IL-6. 11 , 12 , 16 IL-6, considered as one of the most potent inflammatory cytokines, has also been noted to play a critical role in the pathogenesis of various disease processes including rheumatoid arthritis. 10 , 12–14 19,20 Qunzhou et al also found IL-6 to be greatly increased in keloids compared with normal skin.…”