Inborn Errors of Immunity - Innate Flashcards
(20 cards)
What 2 components of the innate immune system can be affected in IEIs?
Phagocytes (predominantly neutrophils)
Complement
IEI Phagocytes:
Describe the 4 types of neutropenic IEI
Chronic Benign Neutropenia
- mild and usually asymptomatic
- associated with some ethnic groups
- no treatment required
Severe Congenital Neutropenia
- heterogenous group of conditions resulting in severe neutropenia
- Autosomal rec defect in HAX1 (kostmann syndrome)
- X-linked defect in WASP
- autosomal dom defect in neutrophil elastase (ELANE)
Cyclic Neutropenia
- Episodic neutropenia every 3-4 weeks
- autosomal dom defect in neutrophil elastase (ELANA aka ELA2)
Shwachman-Diamond Neutropenia
- Autosomal rec defect in SBDS ribosome protein
- Also present with exocrine pancreatic dysfunction
IEI Phagocytes:
Describe the 2 types of non-neutropenic phagocytic IEI
Leukocyte Adhesion Deficiency
- Defect in CD18 causes low beta-2 integrin adhesion molecule on neutrophils. So neutrophils cannot bind to ligand (ICAM-1) on endothelial cells and so cannot transmigrate thorough endothelium of the blood vessel wall to reach the site of inflammation or tissue injury (fail to exit bloodstream)
- very high neutrophil count in blood
- absence of pus formation
Chronic Granulomatous Disease
- Mutation in NADPH oxidase, so phagocytes can’t generate superoxide free radicals (ROS) and so can’t kill bacteria by NETosis after they have been phagocytosed. This means they can’t perform the ‘respiratory burst’.
- Formation of granulomas + hepatosplenomegaly
- unlike LAD, the number of neutrophils is usually normal and pus is present.
- Negative NBT or DHR test
What are the 2 tests for Chronic Granulomatous Disease?
CGD = non-neutropenic phagocytic IEI with mutated NADPH oxidase so cant kill bacteria
2 Tests:
NEGATIVE nitroblue tetrazolium (NBT) test
- aim to stimulate respiratory burst which produces hydrogen peroxide
- NBT is a dye which changes from yellow to blue upon interaction with hydrogen peroxide
- therefore in CGD will remain yellow
NEGATIVE dihydrorhodamine (DHR) flow cytometry test
- aim to stimulate respiratory burst
- DHR would become oxidised to rhodamine which is fluorescent
- therefore in CGD no change in fluorescence seen
Management for neutropenic IEI
Prophylaxis
Granulocyte Colony Stimulating Factor (G-CSF)
Haematopoietic stem cell transplant
Management for non-neutropenic phagocytic IEI
Prophylaxis
CGD: Inteferon gamma therapy
Haematopoietic stem cell transplant
Which IEI is characterised by recurrent infections with no neutrophils on FBC?
Severe Congenital Neutropenia
Susceptibility to encapsulated bacteria may be indicative of what type of immunodeficiency?
Complement immunodeficiency
What is Kostman syndrome?
a type of severe congenital neutropenia (IEI)
Autosomal rec defect in HAX1
What would the most abnormal result on blood count in leukocyte adhesion deficiency?
very high neutrophils
since they cant exit the bloodstream
Which IEI is characterised by recurrent infections with hepatosplenomegaly and abnormal DHT test (no change in fluorescence)?
Chronic granulomatous disease (CGD)
Which IEI is characterised by recurrent infections with high neutrophil count on FBC but no abscess/pus formation?
leukocyte adhesion deficiency (LAD)
A defect in which complement protein is non-problematic?
- Deficient in C9 seem to have no problems because C5, C6, C7, and C8 can lyse a bacterium all on their own, with C9 being icing on the cake!
Which complement deficiency is most associated with developmental SLE?
C1q deficiency
Early and late complement deficiences are respectiviely associated with what?
early complement pathway deficiencies (C1q, C2, C4) in autoimmune diseases like SLE
deficiencies in late complement pathway components (C5-C9) associated with infections, particularly pneumococcal, influenza, and Neisseria infections
Patients with SLE usually present with what complement changes?
Low C3 and C4 since the persistent production of immune complexes results in persistent activation of classical pathway
May also have IEI deficiecny of C1q since this is associated with SLE
What are the standard tests for suspected complement deficiency?
levels of C3
levels of C4
CH50: tests classical complement pathway (Amount of patient serum necessary to lyse 50% of the red blood cells.)
AP50: tests alternative complement pathway (Amount of patient serum necessary to lyse 50% of the red blood cells)
Which complement function test would be abnormal in C1q deficiency?
CH50
Because this tests the classical complement pathway
Which complement function test would be abnormal in C9 deficiency?
Both CH50 and AP50
Because involved in both complement pathways
In which complement pathway is properin found?
Alternative
