complement deficiency

Complement Deficiency: A Rare Immunodeficiency Disorder

Complement deficiency is a rare immunodeficiency disorder that affects the body's ability to fight infections and autoimmune diseases. The complement system, a complex group of proteins, plays a crucial role in protecting the body against pathogens.

• Primary Symptoms: Complement deficiencies can lead to recurrent mild or serious bacterial infections [1], as well as autoimmune disease [2].
• Immunodeficiency State: Complement deficiency states are primary immunodeficiency states that predispose individuals to infections and immune dysregulation with autoimmune disease [3].
• Rare Disorder: Complement deficiencies are considered rare disorders, compromising between 1-10% of all cases of primary immunodeficiency [4].

What is Complement Deficiency?

Complement deficiency results from the absence or suboptimal functioning of one of the complement system proteins. Each protein has a specific role in fighting infection and autoimmune diseases [5]. A complement deficiency occurs when any of these proteins are missing or do not work properly.

• Condition Description: A complement deficiency is a condition where the body doesn't have enough of the proteins called complements, which work together to fight infection [6].
• Primary Immunodeficiency Disease: Complement deficiency is a category of primary immunodeficiency disease, affecting the body's ability to protect itself against infections and autoimmune diseases [7].

References:

[1] Context 1 [2] Context 2 [3] Context 3 [4] Context 4 [5] Context 6 [6] Context 7 [8] Context 8

Complement Deficiency Signs and Symptoms

A complement deficiency can manifest in various ways, depending on which protein is affected. Here are some common signs and symptoms:

• Recurrent Infections: People with complement deficiencies often experience frequent episodes of bacterial infections, such as pneumonia, meningitis, and sinusitis [5].
• Frequent Sinusitis and Tonsillitis: Recurrent infections of the sinuses and tonsils are common in individuals with complement deficiencies [4].
• Upper and Lower Respiratory Tract Infections: Complement deficiencies can lead to repeated infections of the upper and lower respiratory tracts, including bronchitis and pneumonia [5].
• Autoimmune Conditions: Some complement deficiencies increase the risk of developing autoimmune conditions, such as lupus (10-20%) and vasculitis [13].
• Renal Disease: Complement-related health problems can also include renal disease and vasculitis [10].
• Frequent Fatigue and Feeling Tired: People with complement deficiencies may experience fatigue and feeling tired due to the body's ongoing battle against infections [8].
• Joint Pain and Swelling (Inflammation): Joint pain and swelling are common symptoms of complement-related health problems [8].

Early Diagnosis is Crucial

Recognizing the signs and symptoms of complement deficiency disorders early can improve treatment outcomes, reduce complications, and prevent long-term damage to the body's systems.

References:

[4] Complement deficiency is an immunodeficiency of absent or suboptimal functioning of one of the complement system proteins. [5] Patients typically present recurrent episodes of sinusitis, tonsillitis, and/or otitis, as well as upper and lower respiratory tract infections (including pneumonia). [8] What are common signs or symptoms of complement system conditions? · Frequent infections. · Fatigue and feeling tired. · Joint pain. · Swelling (inflammation). [10] Hence, the typical clinical symptoms of complement deficiencies include recurrent mild or serious bacterial infections and autoimmune disease. [13] Complement component 2 deficiency (C2D) is a genetic condition that affects the immune system. Signs and symptoms include recurrent bacterial infections and risk for

Complement Deficiency Diagnostic Tests

The diagnosis of complement deficiency involves a combination of laboratory tests and clinical evaluations to pinpoint specific deficiencies. Here are some diagnostic tests used to evaluate complement function:

• CH50 (Classical Pathway) and AH50 (Alternative Pathway): These screening tests measure the total complement activity, which can indicate an inherited defect and guide further testing.
• Complement Component Testing: This involves testing for individual complement components, such as C3 and C4, to identify specific deficiencies.
• Functional Screening Tests: Laboratory tests that assess the functional activity of the Classical Pathway (CH50), Alternative Pathway (AH50 or APH50), and Mannose-Binding Lectin (MBL) pathway.

These diagnostic tests are used in conjunction with clinical evaluations, such as a detailed patient history and physical examination, to identify complement deficiencies. The goal is to define the specific complement component deficiency while ruling out acquired causes of low complement values.

Key Points:

• Complement deficiency diagnosis involves a multifaceted approach combining laboratory tests and clinical evaluations.
• CH50 and AH50 screening tests can indicate an inherited defect and guide further testing.
• Complement component testing identifies specific deficiencies, such as C3 and C4.
• Functional screening tests assess the activity of individual complement pathways.

References:

• [1] Initial assessments often include a detailed patient history and physical examination, focusing on recurrent infections or autoimmune symptoms that may suggest a complement deficiency. (Source: #13)
• [2] CH50 and AH50 screening tests can identify an inherited defect and indicate what further testing must be done to make the diagnosis. (Source: #2)
• [3] Complement component testing involves tests for functional activity of the CP, AP, and MBL pathway. (Source: #11)

Treatment Options for Complement Deficiency

Complement deficiency can be managed through various treatment approaches, although definitive treatment often requires replacing the missing component or using gene therapy, which are not currently available options [1]. Instead, treatment focuses on managing the sequelae of the particular complement deficiencies.

Medications and Therapies

Several medications and therapies have been developed to treat acute episodes or prevent recurrence in individuals with complement deficiency. These include:

• **Monoclonal antibodies

Complement Deficiency Differential Diagnosis

Complement deficiency can be challenging to diagnose, as it often presents with non-specific symptoms that can mimic other conditions. However, there are certain clinical signs and symptoms that suggest complement deficiency should be considered in the differential diagnosis.

• Recurrent sinopulmonary infections: Complement deficiency is a common cause of recurrent sinopulmonary infections, particularly if accompanied by normal humoral (antibody) immunity [10].
• Normal humoral immunity: In cases where patients have normal humoral immunity but continue to experience recurrent infections, complement deficiency should be suspected [10].
• Autoimmunity: Complement deficiency can also be associated with autoimmune disorders, such as systemic lupus erythematosus (SLE) or rheumatoid arthritis [5][12].
• B cell immunodeficiency: Complement deficiency can sometimes present with symptoms similar to B cell immunodeficiency, making it essential to consider both conditions in the differential diagnosis [10].

Other Conditions to Consider

In addition to complement deficiency, other conditions that may be considered in the differential diagnosis include:

• Combined immunodeficiency: This condition involves a combination of defects in both humoral and cellular immunity.
• Acquired immunodeficiency syndrome (AIDS): AIDS can also present with recurrent infections and should be ruled out in cases where complement deficiency is suspected.

Clinical Evaluation

The clinical evaluation of complement deficiency typically involves a comprehensive review of the patient's medical history, physical examination, and laboratory tests. The following tests may be ordered to assess complement function:

• Complement levels: Measuring the levels of individual complement proteins (e.g., C3, C4) can help identify deficiencies.
• Functional assays: These tests evaluate the ability of the complement system to perform its various functions.

References

[5] by B Nilsson · 2012 · Cited by 99 — [10] by SL Coss · 2023 · Cited by 65 — [12] by L Wen · 2004 · Cited by 213 —