Primary Immunodeficiency Disorders Flashcards
What is the pathogenesis of X-linked SCID?
mutation in gamma chain of IL-2 receptor
What is the common feature in all SCID?
Absent/non-functional T cells
What is the newborn screening test of SCID?
TRECs – non-replicating pieces of DNA in naive T cells generated when making a TCR; number decreased in all SCID and T cell lymphopenia
What is the main gene affected in DiGeorge Syndrome?
TBX1
CATCH-22 Mnemonic for DiGeorge
Cardiac Defects Abnormal facies (microagnathia, low set ears, fish-shaped mouth) Thymic hypoplasia Cleft palate Hypocalcemia 22nd chromosome
Developmentally, where is the defect in DiGeorge syndrome?
1st-6th pharyngeal pouches
Who do you recommend testing for 22q/DS??
ALL infants with significant heart defects
Unexplained lymphopenia
What is the common presentation of XLA?
Boy
No B cells
Recurrent pulmonary infections
What genetic mutation is present in XLA?
Mutations in Bruton’s Tyrosine Kinase Gene (Btk) results in failure in the differentiation of B cells –> usually results in absence of Btk protein
What infections are common in individuals with CVID?
RTI/GI; pulmonary disease– bronchiectasis and interstitial lung disease
Common non-infectious complications of CVID
Lung disease Neoplasia (B cell lymphoma, gastric carcinoma) Autoimmunity GI disease Liver disease
What constitutes a CVID diagnosis?
Low IgG AND low IgA and/or low IgM
What is the most common Ab deficiency?
IgA deficiency
What constitutes IgA deficiency diagnosis?
Low IgA – normal IgG and IgM
What causes false positive results with IgA deficiency?
Heterophile antibodies: antibodies that recognize an antigen different than the antigen that originally induced the Ab response
What is the main clinical finding in individuals with specific antibody deficiency?
abnormal specific antibody response to immunization (especially PS antigens)
What is the pathogenesis of CGD?
An absence of respiratory burst in neutrophils and monocytes – impaired bactericidal killing; defect in NADPH oxidase
What is one presentation that should be considered CGD until proven otherwise?
Hepatic abscess without obvious source in young child
What is unique about mothers of boys with X-linked CGD?
Random X chromosome inactivation occurs so that 50% of the mother’s neutrophils express normal NADPH oxidase and 50% express the defective NADPH oxidase
What are the genetic mutations in LAD-1 and LAD-2?
LAD-1 mutation in common gamma chain
LAD-2 mutation in GDP-fructose transporter which leads to an absence of sialyl LewisX
Will leukocyte count be high or low in leukocyte adhesion deficiency?
High – because there will not be any adhered to endothelium
How do patients with LAD-1 present?
Recurrent pyogenic infections, delayed umbilical cord detachment, leucocytosis, inability to form pus
Those with late complement deficiency are highly susceptible to what bug?
Neisseria
What is the most common complement deficiency?
C2, autosomal recessive
