Genomics of Autoinflammatory Diseases

What are Autoinflammatory Diseases

Autoinflammatory diseases are rare diseases characterised by dysfunction of innate immune system. These are not synonymous with autoimmune diseases which are typically caused by an abnormality of the adaptive immune system.

Autoinflammatory diseases typically have a strong genetic predisposition. A number of genes involved in the development, maturation and functionality of the innate immune system has been implicated. In addition, many of the diseases shown close association with population ancestry and are also therefore prevalent differentially in different parts of the world.

Autoinflammatory diseases presents with recurrent attacks of excessive inflammatory response which manifests as fever, skin rash, arthritis, serositis, conjunctivitis to name a few. These episodes are accompanied by marked elevation of inflammatory markers. Patients are normal in between episodes. Age of onset is usually in childhood and could be a differential for recurrent episodes of fever or pyrexia of unknown origin in children and young adults. Causes for recurrent fever such as infectious, malignancy, autoimmune and factitious are more common and needs to be ruled out. The diagnosis of autoinflammatory needs to be considered in patients with characteristic clinical picture especially if backed by family history and ethnicity.

Why are we doing this ?

Understanding the mutational spectrum of the disease in the Indian context is of prime importance, given the large population, migration and population admixture, prevalent practice of endogamy and population stratification. Apart from a few reports, genetic there has been no data on the genetic epidemiology of the disease in India. Such a landscape would provide the much required data to enable fast and precise diagnosis and allow for appropriate therapy depending on the genetic variation.

Through the feverome project, we aim to systematically characterize genetic variations in families affected by autoinflammatory diseases in India. Genetic analysis would be performed using whole exome sequencing.

We invite you and your Department/Institute to be part of this ongoing collaborative effort. Contact Dr. Vinod Scaria (


Govindaraj GM, Jain A, Peethambaran G, Bhoyar R, Vellarikkal SK, Ganapati A, Sandhya P, Edavazhippurath A, Dhanasooraj D, Puthenpurayil JM, Chakkiyar K, Mishra A, Batra A, Punnen A, Kumar S, Sivasubbu S, Scaria V

Spectrum of clinical features and genetic variants in mevalonate kinase (MVK) gene of South Indian families suffering from Hyperimmunoglobulin D Syndrome

PLoS ONE (2020)

Sharma P, Jain A, Scaria V

Genetic landscape of rare autoinflammatory disease variants in Qatar and Middle Eastern populations through the integration of genomic datasets

medRxiv (2020) .08.10.20171363;

[This is a preprint and presently under peer review]

Koshy R, Sivadas A, Scaria V.

Genetic epidemiology of Familial Mediterranean Fever through integrative analysis of whole genome and exome sequences from Middle East and North Africa

Clinical Genetics (2017) Jan;93(1):92-102. doi: 10.1111/cge.13070

Sandhya P, Vellarikkal SK, Nair A, Ravi R, Mathew J, Jayarajan R, Kumar A, Verma A, Sivadas A, Danda D, Sivasubbu S*, Scaria V*

An Egyptian tale from India - application of whole-exome sequencing in diagnosis of atypical Familial Mediterranean Fever

Int J Rheum Dis (2017) Nov;20(11):1770-1775. doi: 10.1111/1756-185X.13042.