Flashcards in Ch. 6 Autoinflammatory disorders, Amyloid, Granulomatous, & Transplant Deck (73):
gene for FMF?
MEFV (aut recessive)
gene for TRAPS?
TNFRSF1A (aut dominant)
gene for mevalonate kinase deficiency (hyper IgD syndrome or HIDS)
MVK (aut recessive)
gene for CAPS
CIAS1 (aut dominant)
gene for PAPA
PSTPIP1 (aut dominant)
gene for DIRA
IL1RN (aut recessive) - mutation in the IL-1R antagonist
gene for PLAID
PLCy2 (aut dominant)
no gene has been associated with PFAPA, how do you diagnose?
fever 3-6 days q3-8 weeks, exclude cyclic neutropenia, no URI, and at least one of aphthous stomatitis, exudative tonsillitis (neg culture), cervical lymphadenitis
what protein does the MEFV gene produce?
what is the presentation cycle of FMF?
fever 12-72 hrs, peritonitis, pleuritis, arthritis, erysipelas like rash
what is the most serious complication of FMF?
what are the side effects of colchicine?
GI distress, including pain and bleeding.
what is the presentation cycle of TRAPS
fever for WEEKS, myalgia, periorbital swelling, conjunctivitis, headache, abdominal pain, pleuritis with effusion, onset USUALLY in ADULTHOOD
Steroids and TNF monoclonal Ab can be used for TRAPS, T or F?
FALSE - do not work, worsens the flares, use IL-1 blockers
what is the presentation of Hyper IgD syndrome or mevalonate kinase deficiency?
INFANCY, fever 3-7 days, painful LAD, aphthous ulcers, abd pain, arthritis, arthralgia
what can trigger the presentation of HIDS or mevalonate kinase deficiency?
stress and vaccinations
what is the pathologic mechanism by which HIDS is thought to occur?
decrease in isoprenoids, such as geranyl pyrophosphate, leads to overproduction of IL-1B
what 3 aut dominant disorders are included in CAPS (cryopyrin-associated periodic syndromes)?
FCAS and PLAID urticaria is positive using which test?
evaporative cooling test
(ice cube test negative)
hearing loss is present in which two forms of FCAS?
CINCA/NOMID and Muckle Wells
the gene defect PSTPIP1 in PAPA (pyogenic sterile arthritis, pyoderma gangrenous, and acne syndrome) codes for?
CD2 binding protein 1
presentation of PAPA?
early life arthritis, 2nd decade with term symptoms
presentation of DIRA (deficiency of IL-1R antagonist)
neonatal osteomyelitis with rib widening, osteopenia, pustulosis with neutrophil predominance
PLAID has antibody deficiency and cold urticaria, and this is thought secondary to?
diminished signaling at physiologic temp (antibody deficiency) and enhanced signaling at sub physiologic temperatures
high dose antihistamines for urticaria and IVIG if needed
primary amyloidosis involves deposits of what protein?
immunoglobulin light chains
secondary amyloidosis is seen associated with RA, IBD, and what periodic syndromes?
FMF, FCAS, Muckle Wells
Type I cryoglobulinemia contains what type of immunoglobulin
monoclonal IgM > IgG, IgA or light chains
Type II cryoglobulinemia contains what type if immunoglobulin
monoclonal RF (IgM >> IgG)
Type III cryoglobulinemia contains what type if immunoglobulin
polyclonal RF (IgM >> IgG)
what transcription factor has been implicated in the rise of monoclonal B cells and cryoglobulinemia
type I cryoglobulinemia is associated with what two conditions?
plasma cell dyscrasias and multiple myeloma
type II and III cryoglobulinemia is associated with what condition?
hepatitis C (also HBV, HIV)
what are lab markers for granulomas that are not necessarily specific?
high ACE levels, 1,25(OH)2D3, and osteopontin
pulmonary function testing in sarcoid shows what pattern
granulomas in sarcoid show what Th pattern
Th1 non-caseating granuloma
what is Lofgren's syndrome
self limited (3 months) of bilateral hilar adenopathy, erythema nodosum, arthritis/arthralgia
Where are the parenchymal features and nodules in sarcoidosis compared to GLILD?
sarcoid involves upper lung and nodules are hilar, perilymphatic and micronodular. GLILD involves lower lung zones and nodules are large and random
what is a characteristic feature of GLILD which is rarely seen in sarcoidosis?
BAL CD4/CD8 ratio in sarcoid?
BAL CD4/CD8 ratio in HP?
decreased CD4/CD8 (CD8 predominance)
berylliosis results from environmental exposure to?
beryllium (electronics and space industries)
what organs are involved in GPA (Wegener's)
sinus, lung, kidney
what antigen is most commonly present in GPA?
c-ANCA, anti-PR3 antibody
how does EGPA (Churg Strauss) present?
asthma, allergic rhinitis, then eosinophilia, vasculitis is a later finding
HLA-G and HLA-F function?
expressed on extra villous trophoblast, role to protect fetus from maternal immune rejection
direct allorecognition is?
when recipient T cell recognizes donor MHC presenting donor Ag
indirect allorecognition is?
when recipient T cell recognized recipient MHC presenting donor Ag
which solid organ transplants do NOT require immunosuppression?
cornea, bone, and joint tissues
hyper acute solid organ rejection is due to?
pre-existing Ab usually due to ABO incompatibility
accelerated solid organ rejection is due to?
pre-existing Ab due to minor antigens within 2-5 days
acute solid organ transplant rejection is due to?
CD8+T cells directly kill and cell inflammation, after 7 day to 3 months
chronic solid organ transplant rejection is due to
delayed type hypersensitivity like reaction CD4+ T cells resulting in fibrosis, smooth muscle proliferation, occlusion
the mixed leukocyte reaction is used to measure?
presence of host versus graft or graft versus host reaction
for umbilical cord, what is considered a match?
6 out of 6 at A, B, and DRB1 alleles
for adult donors, a match is considered to be?
6 out of 8 match, A, B, C, and DRB1 (note 10 allele matches are more common, adding DQ)
what CD marker denotes stem cells
Which has the higher risk of nonengraftment, matched cord or matched unrelated?
what is the order in ascending risk for allogeneic transplant?
syngeneic < matched 1 degree relative < matched cord < matched unrelated < mismatched cord < mismatched unrelated
what is the survival rate of SCID stem cell transplant prior to 2 months?
95%, after 2 months survival rate declines rapidly
what is the graft versus leukemia effect?
graft/donor T cells eradicate the recipient tumor
how does donor NK cells mediate killing of leukemic cells?
donor NK cells do not recognize the HLA I expressed on leukemic cells and therefore kill them (KIR on NK is not inhibited)
what are the important cytokines in GVHD
IL-10, TNFa, IFNy
what cell is involved in acute GVHD?
CD45RO+ T cells and neutrophils
what cell is involved in chronic GVHD?
CD4+ T cells
presentation of acute GVH?
maculopapular rash, watery diarrhea, abdominal pain, ileum, fever, cholestatic hyperbilirubinemia
the major factor in long term survival in SCT is?
chronic GVH reaction
what complication is associated with conditioning therapy and drug toxicity in SCT?
sinusoidal obstruction syndrome (bilirubin>2mg/dL, hepatomegaly, ascites)
which cell type takes the longest to engraft?
umbilical cord cells
ABPA criteria for IgE in CF?
IgE>2400 ng/mL (>1000 IU/mL) when off steroids
what level is diagnostic for a sweat chloride test in infants and children?
maternal IgG is transplacentally transferred in which trimester?