type I complement component 8 deficiency

Type I Complement Component 8 Deficiency Description

Type I complement component 8 (C8) deficiency is a rare genetic disorder that affects the immune system's ability to fight off infections. This condition is characterized by a malfunctioning immune system, leading to recurrent and severe infections.

Key Features:

• Recurrent Infections: Patients with Type I C8 deficiency are prone to recurring infections, particularly those caused by Neisseria gonorrhoeae (meningococcus) and Neisseria meningitidis.
• Immunodeficiency: The condition results in a form of immunodeficiency, making it difficult for the body to fight off infections.
• Alpha Subunit Deficiency: Type I C8 deficiency is caused by a mutation in the C8A gene, leading to a deficiency of the alpha subunit of complement protein 8.

Symptoms:

• Recurrent moderate to severe swelling in various parts of the body, including extremities, face, lips, larynx (vocal cords), and gastrointestinal tract (intestines).

Causes and Risk Factors:

• Genetic mutation in the C8A gene.
• Inherited from parents who are carriers of the mutated gene.

References:

• [1] Complement component 8 deficiency is a disorder that causes the immune system to malfunction, resulting in a form of immunodeficiency. (Source: #2)
• Patients with deficiency of C8 suffer from recurrent neisserial infections, predominantly with meningococcus infection of rare serotypes. (Source: #6)
• Complement component 8 deficiency is a disorder that causes the immune system to malfunction, resulting in a form of immunodeficiency. (Source: #4)

Recurring Infections and Autoimmune Disorders

People with type I complement component 8 (C8) deficiency are prone to recurring bacterial infections, particularly those caused by Neisseria meningitidis, also known as meningococcus. These infections can be severe and may lead to complications such as meningitis or sepsis [1][2].

In addition to recurrent infections, individuals with type I C8 deficiency may also experience autoimmune disorders, which occur when the immune system mistakenly attacks healthy tissues and organs [3]. This can lead to a range of symptoms, including:

• Glomerulonephritis: Inflammation of the kidneys that can cause damage to the kidney tissue and impair its function.
• Joint problems: Arthritis or other joint-related issues may occur due to the immune system's abnormal response.
• Lung function impairment: Some individuals with type I C8 deficiency may experience lung function problems, particularly those related to the production of mannose-binding lectin (MBL) [4].

It is essential to note that the signs and symptoms of type I C8 deficiency can vary in severity and presentation among affected individuals. Regular medical check-ups and monitoring are crucial for early detection and management of these complications.

References: [1] - 2. [3] - 7. [4] - 8.

Diagnostic Tests for Type I Complement Component 8 Deficiency

Type I complement component 8 (C8) deficiency is a disorder that causes the immune system to malfunction, resulting in a form of immunodeficiency. Diagnosing this condition requires specific tests that can identify the deficiency in the C8 protein.

• Total Serum Classic Hemolytic Complement (CH50) Test: This test measures the function of the complete classical complement pathway, mediated by components C1 – C9 [3]. It is a useful tool to screen for classical pathway deficiencies, including type I C8 deficiency.
• Alternative Hemolytic Complement (AH50) Test: This test can also be used to screen for complement deficiencies, including type I C8 deficiency [4].
• Total Complement Assay (COM/Complement, Total, Serum): This test should be used as a screen for suspected complement deficiencies before ordering individual component tests [4].
• CH50 Functional Test: This test measures the function of the complete classical complement pathway and can help diagnose type I C8 deficiency [7].

Other Tests

In addition to these specific tests, several screening blood tests are available that can make it easier to find the answers. These include:

• CH50: a useful tool to screen for classical pathway deficiencies
• Complement Blood Test: measures the levels and/or activity of a group of proteins that are part of the complement system [8]

References

[1] Available tests. 16 tests are in the database for this condition. [2] Dec 1, 2015 — Complement component 8 deficiency is a disorder that causes the immune system to malfunction, resulting in a form of immunodeficiency. [3] Feb 15, 2022 — One can screen for deficiencies in complement by performing the total serum classic hemolytic complement (CH 50 ) test or the alternative hemolytic complement ... [4] The total complement assay (COM / Complement, Total, Serum) should be used as a screen for suspected complement deficiencies before ordering individual ... [5] Several screening blood tests are available that make it easier to find the answers. [6] Complement component 8 deficiency is a disorder that causes the immune system to malfunction, resulting in a form of immunodeficiency. [7] Nov 9, 2021 — The CH50 functional test measures the function of the complete classical complement pathway, mediated by components C1 – C9. [8] Jun 10, 2024 — A complement blood test measures the levels and/or activity of a group of proteins that are part of the complement system.

Treatment Options for Type I Complement Component 8 Deficiency

Type I complement component 8 (C8) deficiency is a rare disorder that affects the immune system's ability to fight infections. While there are no specific treatments available, various medications and therapies can help manage symptoms and prevent complications.

• Antibiotics: Appropriate prevention and treatment of infections with antibiotics is key [4].
• Fresh Frozen Plasma Infusions: In some cases, fresh frozen plasma infusions have been tried, but they carry a risk of adverse reactions [4].
• C1-Inhibitor Concentrates: For C1-inhibitor deficiencies, substitution therapy exists with several purified C1-inhibitor concentrates available [3][8]. However, bradykinin-receptor antagonists like eculizumab may also be considered.
• Eculizumab: This humanized anti-C5 monoclonal antibody has been approved for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) and may also be beneficial in treating C8 deficiency [10].
• Sutimlimab: As an infusion-based drug, sutimlimab is approved by the FDA for the treatment of cold agglutinin disease (CAD), which shares some similarities with C8 deficiency [6].

It's essential to note that treatment depends on the specific type and severity of complement component 8 deficiency. Consultation with a healthcare professional or an immunologist is necessary to determine the best course of action.

References: [3] P Garred · 2021 · Cited by 131 [4] Appropriate prevention and treatment of infections (usually with antibiotics) is key. [6] by EE West · 2024 · Cited by 40 [8] by P Garred · 2021 · Cited by 139 [10] by T Horiuchi · 2016 · Cited by 88

Differential Diagnosis of Type I Complement Component 8 (C8) Deficiency

Type I Complement Component 8 (C8) deficiency is a rare immunodeficiency disorder characterized by the absence or dysfunction of one of the two subunits of the C8 protein, which plays a crucial role in the complement system's ability to eliminate pathogens. The differential diagnosis for this condition involves considering various clinical manifestations and laboratory findings that may suggest C8 deficiency.

Clinical Manifestations

Individuals with C8 deficiency often present with recurrent bacterial infections, particularly those caused by encapsulated bacteria such as Streptococcus pneumoniae and Haemophilus influenzae [1]. These infections can range from mild to severe and may involve the respiratory tract, skin, or other organs. In addition, some individuals may experience autoimmune manifestations, including systemic lupus erythematosus (SLE) [2].

Laboratory Findings

The diagnosis of C8 deficiency is typically made through laboratory tests that assess complement function and component levels. These tests may reveal decreased levels of C8 protein or impaired complement activity in the presence of C8 [3]. Genetic testing can also identify mutations in the C8A or C8B genes, which are associated with C8 deficiency.

Differential Diagnosis

The differential diagnosis for C8 deficiency includes other immunodeficiency disorders that may present with similar clinical manifestations and laboratory findings. These conditions include:

• C1q deficiency: A rare immunodeficiency disorder characterized by impaired complement function and recurrent infections.
• C2 deficiency: A condition associated with decreased levels of the C2 protein, which can lead to impaired complement activity and increased susceptibility to infections.
• C3 deficiency: A rare immunodeficiency disorder characterized by decreased levels of the C3 protein, which plays a central role in the complement system's ability to eliminate pathogens.

References

[1] Feb 15, 2022 — Differential Diagnoses · Acute Urticaria · Bacterial Sepsis · Complement-Related Disorders · Hypogammaglobulinemia · Immunoglobulin A Deficiency. [2] An even higher percentage of individuals with a deficiency in the CP develop autoimmunity, primarily systemic lupus erythematosus (SLE). A deficiency of C3, the ... [3] The differential diagnosis for these recurrent infections broadly includes B cell immunodeficiency, combined immunodeficiency, acquired immunodeficiencies, as ...