Prakṛti as a Systems Framework for Differential Epigenetic Immune Responses in Autoimmunity: Beyond Genes

Abstract

Autoimmune disorders are multifactorial diseases with a complex interplay between genetic and acquired factors such as immunological, environmental, metabolic, behavioral and other mechanisms. While genome-wide association studies have identified numerous susceptibility loci, genetic variants which rarely explain the observed heterogeneity in disease manifestation and response to treatment. It is the complex interactions between genetic and epigenetic networks, operating together with environmental variables and immune responses, which contribute to an individual’s unique genomic and clinical phenotype.

Ayurveda conceptualizes inter-individual heterogeneity as a key element for understanding physiological and pathological processes. The term Prakṛti refers to an individual’s constitution, which determines his or her physiological and psychological responses to various stimuli. Āhāra-vihāra (dietary and behavioral regimen) and other therapeutic interventions are applied with due consideration of an individual’s Prakṛti to achieve treatment goals. Modern Āyurgenomics has begun exploring the question of whether Prakṛti is associated with specific molecular phenotypes, including, for instance, differences in DNA-methylation patterns reported in a study of healthy Indian men. This raises the interesting possibility that Prakṛti represents a systems biology framework for analyzing the mechanisms by which environmental exposures and immune responses shape inter-individual variation in autoimmune diseases.

This article reviews the emerging evidence for considering Prakṛti, Agni, Āma, and related concepts as systems-level regulators of immune responses in autoimmune diseases. The role of Rasāyana and Panchakarma in modulating these processes is also discussed. It must be emphasized that the present article does not propose to equate Prakṛti with an epigenetic state, or claim that Ayurvedic interventions can “reset the human epigenome.” The author’s position must rather be seen as one of formulating research hypotheses that could inform future studies on autoimmune diseases. Further conceptual and empirical work is needed to test the possibility that Ayurvedic constitutional phenotyping can indeed serve as a framework for precision medicine.