Familial Autoimmune Syndrome (Familial Autoimmunity)

What familial autoimmunity is

Autoimmune diseases happen when the immune system attacks the body's own tissues. There are more than 80 of them, and together they affect roughly 1 in 12 to 1 in 15 Americans, about three-quarters of them women.

Doctors have long noticed that these conditions run in families, but not always the same disease. A mother may have Hashimoto's thyroiditis, a daughter celiac disease and a son type 1 diabetes. This is called familial autoimmunity. When one person has three or more autoimmune diseases, doctors use the term multiple autoimmune syndrome.

Why autoimmune diseases run in families

Shared genes

• HLA genes: these immune genes help the body tell "self" from "non-self". Certain HLA types, such as HLA-DR3 and HLA-DQ2 or DQ8, raise the risk of several autoimmune diseases at once, including type 1 diabetes, celiac disease and autoimmune thyroid disease.
• Other immune genes: variants in genes such as PTPN22, CTLA4 and STAT4 are shared across many autoimmune conditions.

Most familial autoimmunity is polygenic: many small genetic effects add up to a higher risk. No single gene causes it, and most relatives with risk genes never develop an autoimmune disease.

Shared environment

Families share diets, infections, smoking habits and other exposures. Triggers linked to autoimmunity include viral infections, smoking (rheumatoid arthritis, Graves' eye disease), low vitamin D (MS), and gluten in genetically susceptible people (celiac disease).

Sex hormones

Many autoimmune diseases are much more common in women, so female relatives carry a higher risk.

Conditions that often cluster

Rare single-gene autoimmune syndromes

Some families carry a single gene change that causes autoimmunity early in life:

• Autoimmune polyglandular syndrome type 1 (APS-1, or APECED): caused by changes in the AIRE gene. Classic features are chronic candida (yeast) infections, underactive parathyroid glands (low calcium) and Addison's disease, usually starting in childhood.
• IPEX syndrome: caused by FOXP3 gene changes, affecting boys. It causes severe diarrhea, type 1 diabetes and eczema in infancy.
• Autoimmune lymphoproliferative syndrome (ALPS): enlarged lymph nodes and spleen, with autoimmune destruction of blood cells.
• Autoimmune polyglandular syndrome type 2: Addison's disease with thyroid disease or type 1 diabetes, usually in adults, inherited in a more complex way.

These are diagnosed with genetic testing and need specialist care.

Symptoms to watch for

Symptoms depend on which disease develops, but early warning signs that are worth discussing include:

• persistent tiredness
• unexplained weight change
• joint pain, swelling or morning stiffness
• rashes, especially across the cheeks or in sun-exposed areas
• chronic diarrhea, bloating or anemia
• excessive thirst and urination
• patches of skin losing color
• numbness, tingling or vision changes

Diagnosis and screening

There is no single test for familial autoimmunity. Doctors use family history to guide testing:

• Celiac blood tests for first-degree relatives of people with celiac disease, especially if symptomatic, and for people with type 1 diabetes or autoimmune thyroid disease
• Thyroid function tests (TSH) for people with type 1 diabetes and relatives with thyroid disease when symptoms suggest it
• Autoantibody screening for type 1 diabetes in relatives through research programs; a teplizumab infusion can delay the onset of type 1 diabetes in some antibody-positive relatives
• Antinuclear antibodies if symptoms suggest lupus or related diseases (not as routine screening)
• Genetic testing when a rare single-gene syndrome is suspected

Testing healthy relatives without symptoms is only useful when there is an effective early action, such as for celiac disease or type 1 diabetes.

Treatment and management

Each autoimmune disease is treated on its own terms: hormone replacement for thyroid or adrenal failure, insulin for type 1 diabetes, a gluten-free diet for celiac disease, and immune-modifying medicines for lupus, rheumatoid arthritis and MS. People with one autoimmune disease should have periodic checks for common associated conditions.

Reducing risk

You cannot change your genes, but you can reduce some triggers:

• do not smoke
• maintain healthy vitamin D levels
• keep up to date with vaccinations
• maintain a healthy weight

Frequently asked questions

Do autoimmune diseases run in families?

Yes. Relatives of someone with an autoimmune disease are more likely to develop the same or a different autoimmune condition, because they share immune-related genes and some environmental exposures. Most relatives, however, never develop one.

What is familial autoimmune syndrome?

It describes autoimmune diseases clustering within a family. For example, one relative may have thyroid disease and another type 1 diabetes or celiac disease. Rare forms are caused by a single gene change and start in childhood.

What is multiple autoimmune syndrome?

Multiple autoimmune syndrome is when one person has three or more autoimmune diseases. It is often linked to a family history of autoimmunity. Common combinations include thyroid disease, type 1 diabetes, celiac disease, vitiligo and rheumatoid arthritis.

Should I be tested if autoimmune disease runs in my family?

Testing is worthwhile if you have symptoms, or for specific situations such as celiac disease in a parent, sibling or child. Discuss your family history with your doctor, who can recommend targeted tests rather than broad screening.

Are autoimmune diseases inherited from the mother or father?

They can come from either side. Most autoimmune risk is polygenic, with many genes from both parents contributing. Because autoimmune diseases are more common in women, female relatives are often more noticeably affected.