Autoimmune diseases and the genetic factor

Introduction

Autoimmune diseases (AD) are a heterogeneous group of disorders in which the immune system mistakenly attacks the body’s own tissues. Their prevalence is significant—it is estimated that they affect between 7 and 10% of the world’s population. ( Frontiers )
The onset of an autoimmune disease is explained by the convergence of several factors: genetic predisposition, environmental triggers, and failures in the immune response control mechanisms. ( Frontiers )
Genetics plays a crucial role: it is not the only factor, but understanding it allows us to understand the mechanisms, estimate risks, improve diagnoses, and guide personalized therapies.

Why is genetics key in immunology and autoimmunity?

Evidence of heritability

Studies of twins and family members have already shown that ADs have a hereditary component: identical twins have a higher concordance rate than non-identical twins, indicating that genes play a significant role. ( PMC )
This suggests that “having the right genetic variants” increases the likelihood that an environmental and/or immune trigger will lead to the disease.

Multiple genes and polygenesis

AEs are not usually caused by a single gene (except in rare monogenic cases) but by a combination of many genetic variants (alleles), each with a small or moderate effect, which together modulate the risk. ( CNBIOTEC )
For example, the review states:

“The evidence now suggests that genetic susceptibility to common disease is probably due to hundreds or even thousands of alleles…” ( CNBIOTEC )
And also:
“The majority of autoimmune diseases are polygenic…” ( Frontiers )

Main loci involved

There are genetic regions that are frequently associated with AD. For example:

The human leukocyte antigen (HLA) complex on chromosome 6, which plays a central role in antigen presentation to the immune system. ( Frontiers )
Genes such as PTPN22, PTPN2, CTLA4, among others, which regulate T lymphocyte activation, immune tolerance, cytokine signaling, etc. ( Frontiers )
This makes sense from an immunological perspective: if the genes that regulate tolerance or immune activation fail, autoimmunity can be triggered.

Genetic sharing between different autoimmune diseases

A relevant finding is that many genetic variants increase the risk not of just one AD but of several. This implies that different autoimmune diseases share underlying genetic mechanisms. ( PMC )
For example, a variant in an immune-regulating gene can predispose to multiple sclerosis, rheumatoid arthritis, or celiac disease.

Genetics + epigenetics + environment

Genetics does not operate alone: gene expression, their epigenetic regulation (methylation, histone modification, etc.), and interactions with environmental factors (infections, diet, toxins) determine the actual onset of the disease. ( PMC )
In other words, someone may have a genetic predisposition, but a trigger will need to occur for AD to manifest.

What implications does this genetics have on clinical practice and for the patient?

Diagnosis and risk stratification

Knowing genetic risk variants allows:

anticipate the onset of AD in people with a family history,
stratify risk (i.e., differentiate those who are most likely to be),
personalize follow-up (e.g., more intensive surveillance).
For example, polygenic risk scores are being used to quantify AD risk. ( Frontiers )

Understanding pathogenetic mechanisms

By identifying the genes involved, we can better understand how the immune system fails: which pathway, which cell type, which interaction. This is key to designing targeted treatments (precision therapy). For example, failure of Tregs (regulatory lymphocytes) due to mutations in FOXP3, or alterations in interleukin signaling. ( PMC )
This mechanistic understanding can lead to therapies that go beyond general immunosuppression.

Development of targeted therapies

If we know that a specific gene or signaling pathway is altered, we can develop drugs that act on that pathway: for example, cytokine antagonists, modulators of lymphocyte activation, or treatments that restore immune tolerance.
Genetic studies provide “therapeutic targets.”

Prevention and lifestyle

Although genetic inheritance cannot be changed, knowing a predisposition allows us to strengthen the environment (diet, exposure to toxins, infection control) to reduce the “second hit” needed for the disease to manifest.
The 2025 review states that “autoimmune disease develops when three factors converge: genetic predisposition, environmental exposure, and defects in immune regulation.” ( Frontiers )
. Therefore, prevention becomes an important strategy.

Specific examples of diseases and genes involved

Here are some examples to illustrate how genetics is put into practice:

Type 1 diabetes (T1D): This is an AD in which a multitude of risk variants have been identified, both within and outside the HLA family. Genetics accounts for a large part of the risk, although the trigger is usually environmental (viruses, etc.).
Rheumatoid arthritis (RA): Strong association with HLA-DRB1 “shared epitope” and many other genetic variants. ( Wikipedia )
Systemic lupus erythematosus (SLE): Rare single-gene mutations (in severe cases) and many common risk variants have been reported; epigenetic regulation has also been demonstrated. ( PMC )
A recent study identifies 33 HLA genes associated with multiple different ADs. ( Frontiers )
These examples demonstrate that genetics provides a map of risk and mechanism.

What are the current challenges and limitations?

“Missing inheritance” or “missing heritability”

Although hundreds of risk variants have been identified, a significant portion of the heritability of AD remains unexplained. This may be due to: rare variants with large effects, gene-gene interactions, gene-environment interactions, epigenetics, etc. ( PMC )

Incomplete penetrance and clinical variability

Having one or more risk variants does not mean that the disease will develop. Many people with a genetic predisposition will never develop AD, making accurate prediction difficult. The clinical phenotype can vary widely (age of onset, severity, organs affected).

Complexity of gene-environment interaction

Genetics determines everything, but the triggers can be very diverse (infections, microbiome, smoking, diet, toxic exposure). Understanding these interactions is difficult. ( Autoimmune Disease Institute )

Clinical application: still expanding

Although genetic studies are numerous, their translation into clinical practice is still limited: cost, interpretation, variability between populations, and the need for validation.

Population differences

The frequencies of risk variants and their effects may vary by ethnicity, necessitating diverse studies, not just in European populations. ( Nature )

What can a nutrition/health professional (like in your field of nutrigenomics) do with this information?

Even if your focus is on nutrition and nutrigenomics, there are very relevant implications in the immunological/autoimmune field:

You can explain to clients/patients that their genetic predisposition (e.g., AD risk) is an important factor, but it is not deterministic : lifestyle, nutrition, and environment also matter.
In a nutrigenomics project, it is important to consider which genetic variants might influence immune regulation, tolerance, and chronic inflammation—with an eye toward prevention rather than cure.
In genomic sequencing projects (such as the one you are developing), the identification of relevant immunological variants (for example, in lymphocyte regulatory genes, HLA, etc.) could enrich the individual’s risk profile, although it must be handled with rigor and caution.
You can collaborate with immunology professionals to use genetic data from an integrative perspective: genetics + nutrition + lifestyle + environment.
Promote an educational discourse: “This person has a genetic predisposition, so we reinforce immune modulation through nutrition, stress management, a healthy microbiome, and avoiding harmful exposures.”

Conclusion

Genetics is a fundamental pillar for understanding autoimmune diseases: it explains part of the risk, sheds light on the underlying mechanisms of the immune system, and opens doors to prevention, diagnosis, and personalized treatment.
For the field of nutrition and nutrigenomics, this genetic dimension offers an opportunity to integrate knowledge and offer a more comprehensive approach to the patient: not just “what to eat,” but “how my genetics predispose me” and “what can I do to modulate that risk.”
However, it is important to maintain a balanced view: genetic predisposition does not mean inevitability, and clinical translation is still under development. Ethical, rigorous, and personalized application is key.

Recommended studies (direct link)

“Introduction to Genetics of Autoimmune Diseases” — NCBI Bookshelf. Link ( CNBIOTEC )
“Genetic basis of autoimmunity” — JCI. Link ( JCI )
“Emerging patterns of genetic overlap across autoimmune disorders” — Genome Medicine. Link ( BioMed Central )
“Genetic basis of defects in immune tolerance underlying autoimmunity” — Frontiers in Immunology. Link ( Frontiers )
“Autoimmune disease: genetic susceptibility, environmental triggers, and immune dysregulation. Where can we develop therapies?” — Frontiers in Immunology (2025). Link ( Frontiers )