Alpha-1 Antitrypsin Flashcards
What has the potential to produce damage to normal tissues in inflammation?
Leukocyte effector mechanisms
What is the function of alpha-1 antitrypsin?
Mediator of acute inflammation - protein derived
Name the proteins involved in the acute phase response.
Coagulation proteins (fibrinogen) Kinase Complement Lysosomal proteases - elastase from neutrophils and monocytes Alpha-1 antitrypsin
What is the diagnostic marker of general inflammation?
CRP
What does an increased hs-CRP suggest?
Increased risk for heart disease
Describe the correlation between neutrophil elastase and emphysema.
Release of elastase by neutrophils.
Potential damage to elastin in alveoli in lungs
Where is A1A produced?
Hepatocytes in liver and diffuses into tissues
What is the function of A1A?
Serine protease inhibitor - inhibits trypsin in vitro and elastase in vivo
How does A1A work as an elastase inhibitor?
Binds 1:1 with elastase then irreversibly cleaved and inhibition. Suicide inhibitor - A1A is also destroyed.
Subsequent degradation of elastase complex.
Why is there continuous requirement for AAT in inflammation?
It is destroyed - suicide inhibitor.
How does liver damage affect the levels of proteins in the blood.
Decreases levels because of decrease in A1A.
What is the rare disease involving alpha 1 antitrypsin called?
SERPINA1-AAT deficiency (AATD)
State the possible allele combinations of the Common Protease Inhibitor.
PiM = normal
PiZ = most common deficiency allele
PiS = common in some populations (italy)
Pi null = lack the allele
State the phenotypes and risk.
ZZ = very high risk for emphysema or COPD, liver disease e.g. cirrhosis, neonatal hepatitis SZ = increased risk Znull = increased risk MM = reference risk MZ = possible small increase in risk
Describe the genetics of of AAT.
Autosomal recessive, codominant when inherited
Strong genotype, phenotype correlation
