What is Complement Deficiency (Immune Deficiency due to a deficiency in Complememnt Proteins)?
The immune system is like our body’s army, fighting off infections. It has two parts – the innate system and the adaptive system. The innate system is with us from birth and already programmed to function. It consists of different cells like monocytes, macrophages, and natural killer cells, as well as something called a complement system. The adaptive system, on the other hand, develops as we come across infections throughout our life, becoming more efficient with more “experience”. It includes T cells and antibodies produced by B cells. The adaptive system not only gets better at destroying harmful organisms, but also remembers them for future attacks.
Some people have a medical condition called complement deficiencies, which are a form of immune disease that occur when a specific protein in the immune system is missing. This can result in an increased risk of infections and other health conditions, including inflammation and clots in blood vessels.
Additionally, the complement system plays a larger role than just defending against infections. It also helps to prevent diseases related to immune complex, and plays a part in the development of certain diseases like systemic lupus erythematosus (SLE), a condition that causes the immune system to attack its own tissues.
What Causes Complement Deficiency (Immune Deficiency due to a deficiency in Complememnt Proteins)?
Complement deficiencies, which are typically inherited, can result from a variety of conditions. The most common of these is a form of inheritance known as autosomal recessive, which includes deficiencies in complement components C1 through C9 and Mannan-binding lectin. Properdin deficiency follows a different inheritance pattern, known as X-linked recessive.
Complement deficiencies can also be acquired. Some ways this can happen include excessive use of complement, issues with protein synthesis or loss, autoimmune diseases, or high levels of body tissue breakdown.
Complement deficiencies can make you more vulnerable to certain infections. Deficiencies of the early components of the complement pathway are connected with infections from specific types of bacteria like Streptococcus Pneumoniae and Haemophilus Influenza type b. If you are deficient in the complement component C3, you’re more likely to experience frequent severe infections early in life.
Deficiencies in the later stages of the complement pathway put you at risk for Neisseria infections, which include conditions like meningitis and gonorrhea. Deficiency of properdin, an early component in an alternate complement pathway, is also linked with recurrent Neisseria infections. Deficiency of mannose-binding lectin can lead to more frequent severe infections or sepsis, particularly in young children and babies when the immune system is not yet fully developed.
In addition to a higher risk of infection, complement deficiencies can sometimes lead to more autoimmune disorders, specifically systemic lupus erythematosus. This is because the complement system has a role in clearing out body cells that are going through apoptosis, or programmed cell death. If these cells aren’t cleared out, the body may produce autoantibodies against these cells, resulting in autoimmune disorders.
Risk Factors and Frequency for Complement Deficiency (Immune Deficiency due to a deficiency in Complememnt Proteins)
Complement deficiencies, which are quite uncommon around the world, occur in various forms and different populations. At present, if we look at high-risk populations, we can see that the most common type of such deficiency is the mannan-binding lectin (MBL) found in roughly 5% of the White population. These deficiencies often show no symptoms. Aside from this, complement deficiencies occur in about 0.03% of people overall.
The C2 protein deficiency, considered second in frequency after MBL, shows no symptoms as well. One critical player in the understanding of these deficiencies is the C3 protein. This protein is the last step in the early pathway and plays a role in the activation of the complement system. If we see all patients with primary immune system diseases, we find that about 5% have a complement deficiency. Antibody deficiency, which is the most common type of primary immunodeficiency, comprises about 65% of the cases.
When it comes to meningococcal infection cases, almost 30% of patients show a prevalence rate. Those who have a C1q deficiency stand a 93% chance of developing Systemic Lupus Erythematosus (SLE) in the future. Likewise, having a deficiency in C1rs comes with a 57% association with SLE, and a C4 deficiency is associated with a 75% chance of having SLE.
- Properdin and C2 deficiencies are often seen in the White population.
- C6 deficiencies are usually more common in Africans.
- Deficiencies in C8 and C9 are typically seen more in Asian people.
- Specifically, there are two distinct forms of C8 deficiency:
- An alpha-gamma deficiency variant is common among Afro-Caribbeans, Hispanics, and Japanese.
- The C8beta variant is usually observed in Whites.
Signs and Symptoms of Complement Deficiency (Immune Deficiency due to a deficiency in Complememnt Proteins)
If you have frequent infections or certain illnesses, you might have an immune deficiency related to your complement system. Your complement system is part of your immune system that helps or “complements” the ability of antibodies and immune cells to clear pathogens from your body. A complement immunodeficiency can be suspected if you have recurrent infections, especially those caused by the bacterium Neisseria, or if you experience severe recurrent infections early on in life. Frequent sinus and lung infections, along with other abnormal immune responses, may also suggest a complement deficiency.
Infants with a complement deficiency might have Leiner disease, which causes wasting, recurrent diarrhea, and a skin condition called generalized seborrheic dermatitis. Doctors think that this is mainly due to a deficiency in a specific component of the complement system, known as C5, but it also might be due to decreased levels of C3 and reduced movement of immune cells called neutrophils.
A complement deficiency can cause three main problems:
- Inadequate Opsonization: Opsonization is a process that helps your immune system “tag” pathogens for destruction. Complement components, such as C3b and its cleavage product C3bi, play a key role in this process. If these are defective, it can lead to frequent sinus and lung infections, autoimmune syndromes, and infections with specific bacteria such as Neisseria meningitides and Streptococcus pneumonia. Additionally, you might experience other complications, like atypical hemolytic uremic syndrome, membranoproliferative glomerulonephritis, and age-related macular degeneration.
- Defects in Cell Lysis: Cell lysis is the process of breaking down cells. Again, certain proteins in the complement system play a crucial role. Deficiencies here may result in infections that occur later in life, compared to other complement deficiencies, and an inability to effectively combat other kinds of pathogens like viruses, fungi, and mycobacteria.
- Immune Complex Diseases: Lastly, patients deficient in certain components of the complement system are more likely to develop diseases caused by immune complexes. Some potential complications here include seizures related to a form of lupus called neuropsychiatric systemic lupus erythematosus, antiphospholipid antibody syndrome, and arterial thrombosis.
When a doctor examines you, they might not find any abnormalities unless you’re currently experiencing an infection or have an autoimmune disorder. For example, if you have active pneumococcal pneumonia, you might have crackling or bronchial breath sounds when your doctor listens to your lungs. If you have meningitis, you might show signs of irritation of the meninges, which are the membranes that surround your brain and spinal cord. In severe cases, these infections can cause additional problems, like septic shock or disseminated intravascular coagulation, which affects the clotting of your blood. Patients with specific complement deficiencies may also show signs of joint inflammation, indicating an autoimmune response.
Testing for Complement Deficiency (Immune Deficiency due to a deficiency in Complememnt Proteins)
If you find yourself getting sick often, especially with respiratory infections, and there’s no obvious reason why (such as having HIV, a weak spleen, or other immune system issues), it may be a good idea to get tested for complement deficiency. This is also a good idea if you frequently get infections from certain bacteria, like Streptococcus pneumoniae, Neisseria meningitidis, and Hemophilus influenzae, or if someone in your family often gets sick with pneumonia or meningitis.
The tests for complement system include checking for the classical complement pathway, the alternate pathway, and the mannose-binding lectin pathway. If your CH50 is low but your AH50 is normal, it might suggest a deficiency in the early classical complement components. On the other hand, if your AH50 is low but your CH50 is normal, it could signify a deficiency in the early alternative pathway factors. If both your AH50 and CH50 are low, it might indicate a deficiency in the common terminal complement. But if your CH50 and AH50 results are both normal and yet, complement deficiency is still suspected, an MBL functional test can be carried out.
If meningitis is suspected, a head CT scan should be performed before a lumbar puncture. Those with possible deficiencies in the classic complement pathway must be evaluated for consequences of immune complex diseases through a urine test and complete blood count. If there’s still suspicion of meningitis, a lumbar puncture should be conducted to help diagnose bacterial meningitis.
Treatment Options for Complement Deficiency (Immune Deficiency due to a deficiency in Complememnt Proteins)
Complement deficiency is a condition that cannot be typically treated by simply replenishing the complement proteins in the body. This is due to several reasons including impracticality of frequent infusions, the risk of catching infections through the blood, and the chance of the body developing antibodies against the replenished complement proteins. Each case of this condition is managed individually, with antibiotics usually given during episodes of infection. Regular check-ups with an immune system specialist are also essential.
Patients with this condition are particularly vulnerable to certain types of infections, such as those caused by encapsulated organisms, which includes the bacteria causing meningococcal disease. Because of this susceptibility, patients should be aware of the symptoms of meningococcal infection and immediately seek medical attention if these symptoms develop.
Preventive measures such as routine vaccinations against bacterial and viral infections, particularly meningococcal and pneumococcal vaccines, are recommended. These patients do not have any restrictions against live vaccines.
There are instances where patients may experience a sudden worsening of their autoimmune disease condition. In such cases, treatments that suppress the immune system may be needed.
What else can Complement Deficiency (Immune Deficiency due to a deficiency in Complememnt Proteins) be?
When we try to figure out why someone gets infections over and over again, we come up with a list of potential causes:
- Not having a spleen, which can make people more likely to get sick from certain kinds of bacteria
- Different types of B cell immunodeficiency, where the body has trouble producing antibodies to fight off infections
- Combined immunodeficiency, a disease where both parts of the immune system are weak
- Acquired immunodeficiencies, which are conditions that damage the immune system later in life, such as HIV
- Chronic granulomatous disease, a condition that affects white blood cells
- Chédiak-Higashi syndrome, a very rare disease that affects many parts of the body including the immune system
- Leukocyte adhesion deficiency, a condition that affects the immune system’s ability to fight off bacteria and other foreign substances
- Cyclic neutropenia, a condition that affects a type of white blood cell
- Systemic lupus erythematosus (SLE), an autoimmune disease
- Different immunoglobulin deficiencies, which means lacking antibodies that help prevent infections
- Meningococcemia, a serious infection of the bloodstream
It’s crucial for doctors to consider all these possibilities and carry out necessary tests to find the exact cause.
What to expect with Complement Deficiency (Immune Deficiency due to a deficiency in Complememnt Proteins)
The outcome of this medical condition largely depends on how often infections reoccur and how severe they are when they happen. Patients with this condition have a high risk of getting meningitis, which can be life-threatening if not treated.
Possible Complications When Diagnosed with Complement Deficiency (Immune Deficiency due to a deficiency in Complememnt Proteins)
Complications can arise from serious illnesses like pneumococcal and meningococcal infections, which can be deadly if not properly checked and treated. In addition, patients might also face issues with autoimmune disorders, particularly systemic lupus erythematosus.
Complications include:
- Severe pneumococcal infections
- Meningococcal infections
- These infections can be fatal if not evaluated and treated properly
- Development of autoimmune disorders
- Particularly, systemic lupus erythematosus
Preventing Complement Deficiency (Immune Deficiency due to a deficiency in Complememnt Proteins)
Patients and their parents should be made aware of the symptoms of serious illnesses like meningitis, pneumonia, and sepsis. They should be advised to get medical help immediately if any of these symptoms appear. It’s also recommended they get help as soon as possible for less severe infections so that the right antibiotics can be started. Patients might also be given preventive antibiotics for any sudden repeats of an illness. Vaccines are a key way to prevent diseases, particularly for meningitis and pneumonia.
If you have a family member with a complement deficiency, a condition that weakens the immune system, it’s a good idea for you to be tested for it too. Identifying this condition can help prevent potential severe or life-threatening infections. Complement deficiency should be considered in adults diagnosed with a bacterial infection known as N meningitidis. Prompt diagnosis, preventative antibiotics, and getting vaccinated can enable a normal life in case of a genetic disorder called C2 deficiency.