Exploring the relationship between genetics and immune response

Immunogenetics is a branch of immunology exploring the relationship between genetics and responses of the immune system. Genetic sequencing has enabled scientists to identify risk factors for immunological disorders such as rheumatoid arthritis (RA), psoriasis, multiple sclerosis (MS) and systemic lupus erythematosus (SLE), and has greatly improved transplantation practices.1,2

Advances in next-generation sequencing (NGS) technology have accelerated the understanding of how individual candidate genes contribute to the development of autoimmune diseases. Additionally, NGS has improved transplant research by enabling better human leukocyte antigen (HLA) typing, a method critical for stem cell, bone marrow and solid organ transplantation.2

Applications of NGS in autoimmune diseases

Autoimmune diseases are triggered by adaptive immunity through antibodies against the body’s own cells. Multiple genes have been implicated as causative for autoimmune diseases, with environmental factors also playing a significant role.3 Therefore, it’s imperative to analyze epigenetic modifications that occur due to exposure to environmental factors in addition to detecting disease-causing mutations directly. Epigenetic analysis using NGS interrogates the methylation status (Methyl-Seq) or chromatin modification (ChIP-Seq) of candidate genes.

NGS provides high throughput analysis of massive immune repertoires and the ability to identify low-frequency variants, which is important in autoimmune diseases like RA. Whole exome sequencing (WES) has contributed significantly to the identification of rare variants from limited sample sizes in MS, another autoimmune disease.

Use of NGS in HLA typing

In humans, a group of genes encoding HLA, the equivalent of major histocompatibility complex (MHC) in other species, controls the immune responses. HLA aids in distinguishing between self and non-self, and involved in the regulation of innate and adaptive immune response.

HLA typing is a common procedure for assessing compatibility between donor and recipient before organ transplantation. It is also used to identify variants associated with susceptibility of developing genetic immunological diseases.

Considering that the HLA region is the most polymorphic region in the human genome,4 its accurate characterization is critical. Historically HLA typing has been carried out at the phenotypic level, by serological toxicity method using a protease.5 Rapid results is a major advantage of these methods. However, allele-specific information that is critical for HLA typing is not attained with phenotypic tests. Advances in molecular techniques now have enabled allele-level genotypic characterization. NGS has been adopted increasingly as a routine method for HLA typing in transplantation, especially for hematopoietic cell transplantation and solid organ transplantations, where allele-level resolution is critical.4 RNA sequencing (RNA-Seq) is particularly valuable as it provides accurate HLA typing, high throughput and relative HLA gene expression information, which are all important for the outcome of transplantation.4

HLA sequencing using NGS has contributed significantly in immunogenetics, and is especially advantageous in avoiding ambiguous typing results.

Roche provides superior NGS sample preparation reagents to address sample preparation-related issues in HLA typing and other immunogenetics research applications.



  1. Ma Y, Shi N, Li M et al. Applications of next-generation sequencing in systemic autoimmune diseases. Genomics Proteomics Bioinformatics. 2015. 13:242-249.

  2. Bravo-Egna V and Monos D. The impact of next-generation sequencing in immunogenetics: current status and future directions. Curr. Opin. Organ. Transplant. 2017. 22:400-406.

  3. Surace A and Hedrick C. The role of epigenetics in autoimmune/inflammatory disease. Frontiers in Immunology. 2019. doi: 10.3389/fimmu.2019.01525

  4. Edgerly CH and Weimer ET. The past, present and future of HLA typing in transplantation. Methods and Protocols, Methods in Molecular Biology. (ed) Boegal S.2018. Chapter 1. 182:1-10.

  5. Berger A. HLA typing. BMJ. 2001. 322;7280:218.

For Research Use Only. Not for use in diagnostic procedures.