Autoinflammatory Diseases Mediated by NFkB: Causes and Complications

Introduction:

The nuclear factor kappa light chain enhancer (NFkB) of activated B cells is a key involved in many physiological and pathological conditions, including immune responses, programmed cell death, cancer formation, and inflammatory processes. It is involved in rapid responses to a variety of stimuli, including viral and bacterial infections, stress, and numerous cytokines (chemical mediators of inflammation). In the pathology of atherosclerosis, NF-κB is essential for the interactions between cytokines, adhesion molecules, and growth factors leading to the formation, growth, and eventual rupture of atherosclerotic plaques. Autoinflammatory diseases refer to problems with the primary immune system response. Immune cells inadvertently target healthy tissues in the body and signal the body to attack them. This can lead to violent flare-ups of inflammation, leading to symptoms such as high fever, rashes, or swollen joints.

What Are Autoinflammatory Diseases Mediated by NFkB?

NFkB regulates the differentiation of CD4+ T cells, particularly T helper 17 (Th17) cells, which play a central role in the pathogenesis of autoimmunity and inflammation. This causes autoinflammatory conditions in the body. The autoinflammatory syndromes comprise a distinct set of disorders that clinically exhibit recurrent fever episodes accompanied by skin inflammation and mucosal, the inner lining of the organs, bones, and their movements. Although these rare disorders of the immune system often have a striking onset and inflammatory features, they are always without an infectious or autoimmune cause. These disorders are caused by the dysregulation of NF-kB.

What Are the Causes of Autoinflammatory Diseases Mediated by NFkB?

Autoinflammatory conditions occur when the immune system attacks healthy tissues in the body. They can result from a combination of genetics and environment. It appears that people with a genetic predisposition to autoinflammatory conditions can develop the disease if they come in contact with something in their environment that can cause it. However, the cause of autoinflammatory conditions, in most cases, is unknown.

What Are the Risk Factors of Autoinflammatory Diseases Mediated by NFkB?

Researchers do not know what causes autoinflammatory diseases, but several theories indicate that an overactive immune system attacks the body after infection or injury, which has been further shown to increase the chances of developing autoinflammation.

• Genetics - Auto-inflammatory conditions tend to run in families. Having a relative with an autoimmune disease increases the risk.

• Weight - Being overweight or obese increases the risk of developing rheumatoid arthritis or psoriatic arthritis. Being overweight puts more strain on the joints, and the fat tissue produces inflammatory substances.

• Smoking - Research has linked smoking to many autoinflammatory diseases.

• Specific Drugs - Certain blood pressure medications and antibiotics can cause autoinflammatory conditions.

What Are the Symptoms of Autoinflammatory Diseases Mediated by NFkB?

Symptoms of autoinflammatory disease vary depending on the part of the body affected. Many types of autoinflammatory diseases cause redness, swelling, heat, and pain. These are the signs and symptoms of inflammation. However, other diseases can cause the same symptoms.

Symptoms of autoinflammatory conditions come and go. During flare-ups, the symptoms may be severe for some time. Remission may then occur. That is, symptoms improve or disappear over time. Mentioned below are some of the symptoms that a person with an NFkB-mediated autoinflammatory condition might notice:

• Fever.

• Fatigue.

• Joint pain, swelling, and stiffness.

• Rash on the body.

• Shortness of breath.

• Chest pain.

• Dry eyes.

• Headaches.

What Are the Possible Complications of Autoinflammatory Diseases Mediated by NFkB?

The possible complications of autoinflammatory diseases mediated by NFkB production are listed below:

• Infection - Both the disease and its treatment can weaken the immune system, making people with the autoinflammatory disease more susceptible to infections.

• Cancer - Having autoinflammatory disease appears to increase the risk of cancer. However, the risks are small.

• Death of Bone Tissue - It occurs when the blood supply to the bones is reduced, often resulting in small fractures in the bones and, eventually, the bones collapsing.

• Pregnancy Complications - Women with lupus are at an elevated risk of miscarriage. Lupus elevates the risk of high blood pressure during pregnancy and premature birth. To minimize the risk of these complications, physicians recommend postponing pregnancy until the condition is controlled for at least six months.

• Kidney - Autoinflammatory conditions can cause severe kidney damage, and kidney failure is one of the leading causes of death in patients.

• Brain and Central Nervous System - When the brain is affected by autoinflammatory conditions, an individual may experience headaches, dizziness, behavioral changes, blurred vision, and even strokes and seizures. They may have problems and sometimes find it difficult to express their thoughts.

• Blood - Autoimmune conditions can cause problems with blood circulation, such as a low number of healthy red blood cells (anemia) and an increased risk of bleeding and blood clots. It can also cause inflammation of blood vessels.

• Lungs - People suffering from autoinflammatory conditions are more likely to develop inflammation of the lining of the chest, which can make breathing difficult. Bleeding into the lungs or pneumonia is also possible.

• Heart - Autoinflammatory conditions can cause inflammation of the heart muscle, arteries, or heart membrane. There is also an elevated risk of heart attack and cardiovascular diseases.

How Are Autoinflammatory Diseases Mediated by NFkB Diagnosed?

The autoinflammatory disease mediated by NFkB is diagnosed by withdrawing a blood sample from the patient and conducting the tests listed below:

• Electrophoretic Mobility Shift Assay (EMSA) - It is a rapid and sensitive method to detect protein-nucleic acid interactions

• NFkB Reporter Kit - It is used to monitor the activity of the NFkB signaling pathway in cultured cells. Monitoring the movement and levels of NFkB is done by this kit.

• Enzyme-linked immunosorbent assay (ELISA) - This immunological test is highly sensitive and is used to detect and quantify substances such as antibodies, antigens, proteins, and hormones.

How Are Autoinflammatory Diseases Mediated by NFkB Treated?

Non-steroidal anti-inflammatory drugs, like Aspirin and Sodium salicylate, are known inhibitors of NFkB. They act by blocking the pathway of NFkB. Doctors use these medications to inhibit NFkB proliferation and impede the auto-inflammatory response of the body. NSAIDs cannot be used for more than three days. These medications are intended for short-term use.

Conclusion:

Autoinflammatory diseases mediated by NFkB are a group of diseases that occurs when the body's immune system is affected by dysregulation of the NFkB pathway. Inflammation caused by this autoinflammatory condition can affect a variety of body systems, including joints, skin, kidneys, brain, heart, lungs, and blood cells. Autoinflammation can be hard to diagnose because its signs and symptoms resemble those of other disorders. The signs and symptoms of autoinflammation mostly resemble that of autoimmune conditions. Protein enzyme is the only way to diagnose this condition. Early and proper diagnosis of this condition can prevent long-term damage to the organs.