38 Questions
Which complement component deficiency is most likely to decrease immune complex clearance?
C1
In the case of the 15-year-old female with recurrent Neisseria meningitidis infections, which complement component deficiency is most likely?
C5
Which complement component deficiency is associated with increased susceptibility to recurrent infections, similar to the case of the 15-year-old male with occipital headache, stiff neck, and vomiting?
Properdin
In the context of abnormal CH50 and AH50 results, which complement component deficiency is most likely present in these patients?
C3
What is the function of the C1q subcomponent in the classical pathway of complement activation?
It cleaves C4 and C2
What initiates the lectin pathway of complement activation?
Binding by lectins to repetitive sugars on microbial surfaces
In the alternative pathway, what process continuously self-activates at a low level?
C3 tickover
Which component takes the place of the C1 proteases in the lectin pathway of complement activation?
Mannose-associated serine proteases (MASPs)
What is the inheritance pattern for C1q deficiency?
Autosomal recessive
Which condition is associated with C1q deficiency?
Systemic lupus erythematosus (SLE)
What is the result of C1q deficiency on the CH50 test?
CH50 = 0
Which complement pathway activation is defective in C1q deficiency?
Classical pathway
What is a common clinical manifestation of C1q deficiency?
Hyperpigmentation; skin fragility
Which complement protein is involved in C1q deficiency?
C4A + C4B
What type of mutations predispose to systemic lupus erythematosus (SLE) in C1q deficiency?
Biallelic mutations, deletions, or conversions of both C4A and C4B
What are the OMIM features associated with C1q deficiency?
217000
Which receptor is affected by C1q deficiency?
CR2
What is the result of AP activation in C1q deficiency?
AP activation; C3 consumption
Which complement protein is associated with increased complement activation in C1q deficiency?
Factor H
Which complement pathway activation is defective in MBL2?
Lectin pathway
What forms the C3 convertase in the classical pathway of complement activation?
C4bC2b
Which component replaces the C1 proteases in the lectin pathway of complement activation?
Mannose-associated serine proteases (MASPs)
What initiates the alternative pathway of complement activation?
Continuous self-activation at a low level
What results from the binding of another C3b to the C3 convertase in the alternative pathway?
Formation of the C5 convertase
Which complement protein deficiency is associated with an increased risk of severe, recurrent pyogenic sinus and respiratory tract infections?
C3b deficiency
What is the characteristic clinical manifestation of hereditary angioedema due to C1 esterase inhibitor deficiency?
Unregulated activation of kallikrein
Which complement inhibitor is prevented from forming due to a defect in the PIGA gene in paroxysmal nocturnal hemoglobinuria?
Membrane inhibitor of reactive lysis (MIRL/CD59)
Which complement component deficiency can cause complement-mediated intravascular hemolysis and atypical venous thrombosis?
C4 deficiency
What is the result of C1Q deficiency on the CH50 test?
Decreased CH50
Which complement component deficiency is associated with hyperpigmentation and skin fragility?
C2 deficiency
In C1S gain of function (GOF), what is the result of CH50 test?
Normal CH50
Which disorder is associated with mannose-binding lectin (MBL) deficiency?
Pyogenic infections
What clinical manifestation is common in patients with C1 inhibitor deficiency?
Spontaneous activation of complement
Which complement component deficiency leads to excessive AP activation and decreased CD46 levels?
Factor H-related protein deficiencies
What are the OMIM features associated with C4A and C4B deficiency?
CH50 = 0; CP defective activation SLE; infections with encapsulated organisms; Ehlers-Danlos phenotype
Which receptor is affected by C1q deficiency?
CR2
What initiates the lectin pathway of complement activation?
MBL2 mutations
What type of mutations predispose to systemic lupus erythematosus (SLE) in C1R deficiency?
Autosomal dominant (AD) gain of function (GOF) mutations
Study Notes
- The text is from "Immunology Scope Monograph" about Inherited Disorders of the Complement System published by UpToDate in 1992.
- The complement system has three major pathways for activation: classical, lectin, and alternative.
- In the classical pathway, immune complexes bind C1, which then cleaves C4 and C2 to form C4bC2b and C3 convertase, resulting in C3a and C5 convertase.
- In the lectin pathway, lectins bind to repetitive sugars on microbial surfaces, activating mannan-binding lectin-associated serine proteases (MASPs) instead of C1 proteases.
- The alternative pathway continuously self-activates at a low level (C3 tickover) and generates C3b, which engages alternative pathway components to form C3 convertase and C5 convertase.
- A deficiency in C3 is most likely to decrease immune complex clearance.
- A 15-year-old female presents to the ED with meningitis caused by Neisseria meningitidis, and her CH50 and AH50 results are abnormal.
- The complement component most likely to be deficient in this patient is Mannose-binding lectin (MBL) or Properdin.
- Early complement deficiencies, such as C1-C4, increase the risk of severe, recurrent pyogenic sinus and respiratory tract infections, and SLE.
- Terminal complement deficiencies, such as C5-C9, increase susceptibility to recurrent Neisseria bacteremia.
- Complement regulatory protein deficiencies, such as C1 esterase inhibitor deficiency, cause hereditary angioedema due to unregulated activation of kallikrein and bradykinin, and characterized by low C4 levels. Paroxysmal nocturnal hemoglobinuria is a defect in the PIGA gene that prevents the formation of glycosylphosphatidylinositol (GPI) anchors for complement inhibitors, such as decay-accelerating factor (CD55) and membrane inhibitor of reactive lysis (CD59), causing complement-mediated intravascular hemolysis and dark urine. It can also cause atypical venous thrombosis, such as Budd-Chiari syndrome, portal vein, cerebral, or dermal thrombosis.
- The text mentions various complement components, pathways, and disorders, including C1, C4, C8, CH50, AH50, MBL, MASP-1/MASP-2, properdin, SLE, aHUS, and PNH.
- Various genetic inheritance patterns are mentioned, including autosomal recessive, autosomal dominant, X-linked recessive, and linked deletions.
Test your knowledge of inherited disorders of the complement system with this quiz. Explore the genetic inheritance, protein deficiencies, associated diseases, and laboratory features related to complement deficiencies.
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