Autoinflammatory Diseases Panel

Genetic testing for autoinflammatory diseases at IntroLab in Belgrade enables early detection and precise diagnosis of these complex disorders. Personalized result interpretation forms the basis for optimal clinical management and enhances the quality of life for patients.

What are autoinflammatory diseases?

Autoinflammatory diseases are a group of rare disorders of the innate immune system that cause chronic or episodic inflammation without the presence of infection or autoantibodies. These diseases are characterized by frequent episodes of inflammation, which can affect multiple organ systems, including the skin, joints, gastrointestinal tract, and internal organs.

What causes autoimmune diseases?

Autoimmune diseases occur when the immune system, which is responsible for protecting the body from pathogens like bacteria and viruses, mistakenly starts attacking the body’s own cells and tissues. This phenomenon usually results from a combination of genetic predisposition and environmental factors. Genetic variations can increase the risk for certain individuals to develop autoimmune diseases, but environmental triggers, such as infections, exposure to toxins, or hormonal changes, are often needed to initiate the autoimmune response. Chronic stress can also play a role in triggering autoimmunity, leading to an imbalance in the immune system.

Types of autoimmune diseases

Autoimmune diseases encompass a wide range of conditions, with some of the most common types including:

• Rheumatoid arthritis: A chronic inflammatory disease that primarily affects the joints, causing pain, swelling, and deformities.
• Lupus (Systemic Lupus Erythematosus): A disease that can affect multiple organs and systems, including the skin, joints, kidneys, and brain.
• Multiple sclerosis: A disease that affects the central nervous system, leading to problems with movement, coordination, and other neurological functions.
• Type 1 diabetes: An autoimmune disorder where the immune system attacks the beta cells in the pancreas that produce insulin, leading to high blood sugar levels.
• Celiac disease: An autoimmune reaction to gluten, a protein found in wheat, barley, and rye, which damages the small intestine.

Autoinflammatory vs. Autoimmune diseases

Although autoinflammatory and autoimmune diseases can have similar symptoms, such as inflammation and joint pain, they differ in their underlying mechanisms:

Autoinflammatory diseases affect the innate immune system, which serves as the body’s first line of defense. These diseases arise due to mutations in genes that regulate inflammatory responses, causing inappropriate inflammation without a specific trigger. Examples include Familial Mediterranean Fever and TRAPS (Tumor Necrosis Factor Receptor-Associated Periodic Syndrome).

Autoimmune diseases involve the adaptive immune system, which mounts specific responses to pathogens using antibodies. In autoimmune diseases, the immune system mistakenly identifies the body’s own cells as foreign and attacks them. Examples include rheumatoid arthritis and lupus.

Genetic testing for autoinflammatory diseases

Our panel for autoinflammatory diseases includes the analysis of the following key genes associated with various autoinflammatory syndromes:

ACP5, ADAM17, ADAR, CARD14, CECR1, COPA, DDX58, DNASE1L3, DNASE2, ELANE, IFIH1, IL10, IL10RA, IL10RB, IL1RN, IL36RN, ISG15, JAK1, LPIN2, MEFV, MVK, NLRC4, NLRP1, NLRP12, NLRP3, NOD2, OTULIN, PLCG2, POMP, PRG4, PSENEN, PSMB4, PSMB8, PSTPIP1, RIPK1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, SLC29A3, TMEM173, TNFAIP3, TNFRSF1A, TREX1, TRNT1, TTC7A, UBA1.

Identifying mutations in these genes allows for accurate diagnosis, prognosis, and the selection of personalized therapeutic approaches.

Typical symptoms of autoinflammatory diseases

Symptoms of autoinflammatory diseases can vary widely, but some of the most common include:

• Frequent fevers: Recurring episodes of elevated temperature, often without an obvious cause.
• Rashes and skin lesions: Redness, painful nodules, and hives (urticaria).
• Joint and muscle inflammation: Pain and swelling in the joints and muscles, often accompanied by stiffness.
• Gastrointestinal problems: Abdominal pain, diarrhea, and vomiting.
• Inflammation of internal organs: This may include damage to the liver, spleen, or kidneys.

How is genetic testing performed?

Genetic testing is conducted through several steps:

• Sample collection: An EDTA blood sample is collected and sent for analysis.
• NGS library preparation: DNA is fragmented, and specific adapters are added for sequencing.
• NGS sequencing: The DNA is sequenced using advanced bioinformatics tools.
• Data analysis and interpretation: The results are interpreted by geneticists with specialized expertise in autoinflammatory diseases.

Who should consider testing for autoinflammatory diseases?

Testing is especially beneficial for the following groups:

• Patients with unexplained inflammatory symptoms: Individuals who have frequent fevers, rashes, or joint pain without a clear cause.
• Families with a history of autoinflammatory diseases: Identifying carriers of mutations can help in the prevention and early detection of these diseases.
• Clinicians and researchers: It supports the development of personalized therapies and enhances the clinical management of patients.

Advantages and limitations of genetic testing

Genetic testing provides significant benefits for diagnosing and treating autoimmune and autoinflammatory diseases. The high accuracy of these tests allows for the precise identification of genetic mutations, thanks to advanced technologies like next-generation sequencing (NGS). This enables the early detection of predispositions to certain diseases, allowing healthcare providers to start treatment in the early stages, when therapy is often more effective.

However, genetic testing also has its limitations. The presence of a genetic mutation does not necessarily mean that a person will develop the disease; it only indicates an increased risk. Additionally, interpreting the results can be complex and often requires expert analysis, as many factors, including environmental influences, can affect disease outcomes. Moreover, genetic tests are sometimes limited to specific genes and may not cover all possible genetic mutations associated with a particular disease, which can impact the comprehensiveness of the analysis.

Therapeutic approach and monitoring

After identifying genetic mutations, the therapeutic plan may include:

• Anti-inflammatory therapies: Such as NSAIDs and corticosteroids to manage inflammatory episodes.
• Biologic drugs: In cases where specific inflammatory pathways are involved, biologic drugs, such as IL-1 or TNF inhibitors, may be used.
• Patient monitoring: Regular monitoring of patients’ conditions to adjust therapies promptly according to disease progression.

Genetic testing panels at IntroLab

IntroLab in Belgrade offers a variety of genetic testing panels based on NGS technology. These panels are crucial for identifying various hereditary disorders and genetic diseases:

• Cardiomyopathy panel
• Arrhythmia panel
• Marfan syndrome panel
• Epilepsy panel
• Clinical exome sequencing
• Molecular karyotyping

Prenatal tests at IntroLab

In addition to genetic panels, IntroLab offers a wide range of prenatal tests based on NGS technology. These tests allow for the early and accurate detection of various genetic abnormalities during pregnancy:

• Prenatal BASIC Test
• Prenatal PLUS Test
• Prenatal EXPERT Test
• Prenatal PREMIUM Test
• Prenatal SPECIAL Test
• Prenatal SPECIAL + SMA Test

These prenatal tests are designed to provide a comprehensive overview of fetal health by identifying chromosomal abnormalities and other genetic disorders that may affect the baby’s development.