PID Flashcards
in xla, defects in b lymphocyte development result in __
- severe hypogammaglobulinemia
- absence of circulating b cells
- small to absent tonsils
- no palpable lymph nodes
protein affected in xla
burton tyrosine kinase (btk): expressed at high levels in all b lineage cells and myeloid series
suspect xla if:
- lymphoid hypoplasia on pe
- serum igg, iga, igm, ige are below 95% confidence limits
- low levels of natural antibodies to type a and b rbc polysaccharide
- low antibodies to immunizations
- absence of b cells in flow cytometry
treatment for xla
- replacement of immunoglobulin
- general supportive care
t/f cvid has only one genetic component
false, composed of several defects with autosomal dominant inheritance.
common: iga deficiency
clinical manifestations of cvid
- autoantibody formation
- normal sized or enlarged tonsils and lymph nodes
- recurrent/chronic infections
most common well defined immunodeficiency disorder
selective iga deficiency
genetics of selective iga deficiency
- autosomal dominant
- common in people with cvid (iga d -> cvid)
clinical manifestations of iga deficiency
- infections in the respiratory, gi, and urogenital tracts
- normal other igs
- igg against cow’s milk and ruminant serum proteins
- celiac like syndrome
- autoantibodies and malignancy higher risk
diagnosis and treatment for iga def
- diagnose only in >4 yo with low iga, normal igg ang igm
- can have elevated igm and low igg2
can resolve spontaneously
tx: 5 times washed normal donor erythrocytes OR blood products from other iga deficient individuals
IVIG NOT INDICATED
treatment of choice for patients with primary t cell defects
transplantation of thymic tissue or mhc or half-matched parental hematopoietic stem cells
thymic hypoplasia results from __
dysmorphogenesis of 3rd and 4th pharyngeal pouches during early embryogenesis -> hypoplasia/aplasia of thymus and parathyroid glands
catch 22 syndrome
cardiac defects abnormal facies thymic hypoplasia cleft palate hypocalcemia
charge association
seen in complete digeorge syndrome
- Coloboma
- Heart defect
- choanal Atresia
- growth or developmental Retardation
- Genital hypoplasia
- Ear anomalies (deafness)
clinical manifestations of digeorge syndrome
- suggested by hypocalcemic seizures during neonatal period
- partial: infections but grow normally
- complete: like severe combined immunodeficiency (opportunistic infections + gvhd from nonirradiated blood)
diagnosis and tx of digeorge syndrome
- low cd3 t cell
- low for age absolute lymphocyte
- pcr based genotyping (TBX1)
tx: cultured unrelated thymic tissue transplants, nonirradiated unfractionated bone marrow, peripheral blood transplants from hla-identical sibling
pathogenesis of scid
mutation in genes that encode components of immune system crucial for lymphoid cell development
clinical manifestations of scid
- extremely low or absent t cells and ig
- recurrent or persistent diarrhea, pneumonia, om, sepsis in first months
- opportunistic infections
- gvhd
- diagnosed with nbs
treatment for scid
hla-identical or t cell depleted haploidentical parental hematopoietic stem cell transplant
distinguishing features of ada scid
- affects primarily t cell function (normal nk and b cells)
- rib cage abnormalities
- abnormalities of chondro-osseous dysplasia
distinguishing features of reticular dysgenesis
- <1 g thymus, no hassall corpuscles, no thymocytes
- adenylate kinase 2 mutation
- tx: myeloablative matched sibling bone marrow transplant
how to distinguish cid and scid
cid has low but not absent t cell function, neutropenia and eosinophilia
characteristics of wiskott aldrich syndrome
wiskott and aldrich have ABS
- atopic dermatitis
- (bleeding diathesis) thrombocytopenic purpura with normal appearing megakaryocytes but small defective platelets
- susceptibility to infection (opportunistics)
cells affected in wiskott aldrich syndrome
- platelets: microthrombocytopenia = excessive bleeding
- helper t cells and b cells = impaired immune response
- t cells and nk cells = impaired defense to pathogens and cancer
normal or low igg and igm, high ige and iga
dx and tx for wiskott aldrich syndrome
- dx: peripheral smear showing microthrombocytopenia and genetics showing mutated wasp gene
- tx: bone marrow or cord blood transplantation
cells affected in ataxia telangiectasia
tb 3/4 8! gamma! delta!
thymus
- depressed t and b cell
- cd3 and cd4 t cells reduced
- cd8 normal or increase
- gamma/delta t cells elevated
- thymus: hypoplasitc, unorganized, no hassall corpuscles
triad in ataxia telangiectasia
3As
- cerebellar Ataxia
- spider Angiomas
- igA deficiency
characteristic clinical features of hyper ige syndrome
SPOUC 2000
- staph abscesses
- pneumatoceles
- osteopenia
- unusual facial features
- candida infection 2nd most common
- ige >2000 iu/ml
gene affected in autosomal dominant hyper ige
stat 3
tx for hyper ige syndrome
- long term administration of penicillinase resistant antistaph antibiotic
- ivig, thoracic surgery, bone marrow transplant
characteristics of lad
- recurrent bacterial and fungal infection
- slow healing ulcers
- omphalitis (umbilical cord infection)
- neutrophil leukocytosis >25,000/mm3
gene mutations in lads
lad 1: integrin b2 common chain (cd18)
lad 2: fucosylated proteins (sialyl lewis x, cd15s)
lad 3: kindlin 3 (integrin)
features unique to lad 2
- neurologic deficits
- cranial facial dysmorphism
- absence of erythrocyte abo blood group antigen
diagnosis of lad
flow cytometry for cd11b/cd18/ sialyl lewis x
treatment for lad
- early allogeneic hsct for lad 1 and 3
- maintenance tmp-smx
genetics of chediak-higashi syndrome
- lysosomal traffic regulator mutated (lyst)
clinical manifestations of cheidak higashi
- partial oculocutaneous albinism
- solar sensitivity
- photophobia
- neuropathy
- prolonged bleeding times
accelerated phase of chediak higashi syndrome
- genetic form of hemophagocytic lymphohistiocytosis
- pancytopenia
- high fever
- lymphohistiocytic infiltration of liver, sppleen, and lns
diagnosis of cheidak higashi syndrome
- large inclusions in all nucleated blood cells
- progressive neutropenia
- abnormal platelet, neutrophil, and nk function
treatment for cheidak higashi syndrome
- high dose ascorbic acid
- hsct is curative
genetic etiology of chronic granulomatous disease
- cybb = gp91
- ncf1 = p47
- ncf 2 and cyba = p67 and p22
pathogenesis of chronic granulomatous disease
- cannot kill catalase positive microorganisms
- no hydrogen peroxide
- s aureus!!!, serratia marcescens, b cepacian, aspergillus, c albicans, nocardia, salmonella, mycobacterium
clinical manifestations of chronic granulomatous disease
- granuloma formation and inflammatory processes!!
- recurrent pneumonia
- lymphadenitis
- hepatic / sc abscess
- osteomyelitis at multiple sites
- fhx of recurrent infections
- infection with unusual catalase positive organism
treatment for chronic granulomatous disease
- hsct: curative
- gene therapy
- tmp-smx, interferon y, itraconazole
