Chapter 7 - Immunogenetic perspective of inflammatory disorders

Abstract

Understanding of the genetic basis underlying inflammatory disorders has progressed in recent years. Contribution of proinflammatory cytokines, human leukocyte antigen (HLA), and non-HLA polymorphisms in the pathogenesis of several autoimmune and immune-mediated inflammatory disorder is critical. HLA plays a central role in disease pathology. Harmful stimuli triggering the signaling mechanisms including nuclear factor-kappa B pathway, Janus kinase-signal transducer and activator of transcription pathway, and mitogen-activated protein kinase pathway results in the release of inflammatory mediators. From acute to chronic inflammation, the etiology of various inflammatory disorders is poorly understood. Inflammatory disorder such as COVID 19 is a devastating havoc to the world. As we reach the end of 2020, >1 million people have succumbed to death worldwide. Disease-manifesting clinical features include mild to severe pneumonia, loss of respiratory function progressing to acute respiratory distress syndrome with occasional multiorgan failure. Cytokine storm, decreased T cell count, and insufficient immune response are conducive issues to COVID 19 pandemic. Varied immune responses to the same antigen across different individuals determine the genetic perspective of disease susceptibility. Through genome-wide association studies, next-generation sequencing and other genetic techniques, several genetic risk loci associated with various inflammatory diseases such as inflammatory bowel disease, psoriasis, sclerosis, and systemic lupus erythematosus (SLE) have been identified. Dysregulated inflammatory pathways, gene mutation, or elevated cytokine level may lead to the disease progression. However, the production of autoantibodies against the nuclear antigens is a hallmark of diseases like SLE and rheumatoid arthritis. Moreover, environmental factors like smoking also increase the risk of inflammatory disorders. Understanding the functional aspects of casual genetic factors underlying the disease pathogenesis greatly facilitates the ability to identify the therapeutic targets relevant to disease. The current chapter deals with the idea of genetic perspective associated with various inflammatory disorders and their potential therapeutic targets along with the factors contributing to disease susceptibility.