Flashcards in Ch. 6 Immunologic Disorders Deck (61):
what is the inheritance and gene mutation for hereditary angioedema?
AD; mutation of chromosome 11 C1-INH gene (SERPIN1); heterozygous mutations leading to either absent (type I) or non-functional (type II) protein expression
what is the gene mutation associated with normal C1INH and complement levels?
mutation of Factor XII gene
what are the two FDA approved plasma-derived C1INH concentrates?
Cinryze (approved for long term prophylaxis) and Berinert (for acute attacks)
what therapy for HAE is recombinant C1INH?
Ruconest; acute attacks; be cautious in Rabbit allergy
what therapy for HAE has a black box warning?
ecallantide (Kalbitor)- kallikrein inhibitor; BBWarning for anaphylaxis in 3-4% of of patients
what is the mechanism of action for icatibant (Firazyr)?
bradykinin antagonist (acute attacks); may be associated with MERGX2 receptor
what distinguishes acquired angioedema from hereditary?
low C1q level; type I (paraneoplastic) type II (autoantibody)
HIV Co-receptor that is monocyte/macrophage tropic
CCR5 (also known as M tropic)
HIV co-receptor that is T cell tropic
what adhesion molecule on dendritic cells does the gp10 HIV glycoprotein bind
what test is used for an HIV exposed infant?
HIV DNA PCR; may also be used in acute viral syndrome prior to Ab test accuracy; infants should be tested serially (2-3 wks, 1-2 mos, 4-6 mos); with HIV Ab test at 12-18 mos to definitively rule out.
what can lead to a false positive HIV ELISA (screening test with high sensitivity)?
autoimmune disease, multiple pregnancies, multiple transfusions, recent imms. can have false negatives within window period (up to 6 months after being infected)
what is the confirmatory test for ELISA or Rapid HIV test?
Western Blot; requires 2 or 3 major bands (anti-p24, anti-gp41, anti-gp160/120
which HIV medication is a strong CYP3A4 and CYP2DG inhibitor that can cause Cushings from intranasal steroids?
what is the HLA type that needs to be screened for prior to initiating abacavir?
what is immune reconstitution inflammatory syndrome (IRIS)?
it is a cytokine storm that develops with CD4 T cells rapidly increase after initiating HIV therapy; may be in response to pre-existing opportunistic infections (PJP, TB, MAC, CMV, herpes)--> need to be controlled prior to initiation of HAART to prevent IRIS?
which chemokine has been heavily implicated in EOE?
eotaxin-3 (induced by IL-13); may also be SNP variants in TSLP
what is the negative and positive predictive value of milk SPT in EOE?
milk NPV <30%; PPV > 86&; all other foods have poor PPV
features of myeloproliferative HES
mostly in males; high risk of cardiac complications; FIP1-> PDGFRA mutations (aka chic 2); deletion on 4q12; jak2 mutation; biomarkers= Increased B12; tryptase may be elevated; first line treatment in chic2 mutation is imatinib (tyrosine kinase inhibitor)
features in lymphocytic HES
derm; usually benign, but can progress to T cell lymphoma; T cell polyclonal population (clonal TCR rearrangement) expressing IL-5
what is critical prior to initating empiric treatment with glucocorticoids in HES?
rule out and/or empirically treat for Strongyloides prior to systemic GCs
what is urticaria pigmentosa?
brownish macules/nodular lesions with characteristic Darier's sign
what is diffuse cutaneous mastocytosis?
thickened, brownish-yellow skin, less likely to have discrete lesions; usually in pediatric population and is outgrown without progression to systemic mastocytosis
what is the molecular pathogenesis of systemic mastocytosis?
activating (constitutive) mutation of ckit (e.g. KITD816V); leads to aberrant expression of antiapoptotic proteins (Bcl-2 and Bcl-XL)
what is the CD nomenclature for c-kit and what is the ligand?
CD117; binds stem cell factor
what are the major and minor criteria for systemic mastocytosis?
Major: biopsy with >15 mast cells in aggregates
Minor: >25% with atypical or spindle-shaped morphology; detection of ckitD816V mutation; expression of CD2 or CD25 on CD117+ mast cells (i.e. activation markers), total serum tryptase >20
Need one major or 3 minor
what are the urine tests for MCAS?
24 urine histamine; PGD2 or its downstream metabolite (11 beta prostaglandin F2alpha)
what are two clinical uses for imatinib in allergy/immunology?
FIP1L1-PDGFRA mutation in myeloproliferative HES; in systemic mastocytosis (aggressive) WITHOUT ckit mutation
under what circumstances do you need to pursue pcn desensitization with syphillis?
pregnant patient with syphillis, neurosyphillis, congenital syphillis. In other situations, patients can be treated with doxycycline, azithromycine or ceftriaxone
when might you see a false positive non-treponemal test for syphillis?
pregnancy, IV drug use, other infections (TB, other treponemes, rickettsia, HIV) or endocarditis
what key mediator differences will you see in CRS w NP? W/o NP?
With/out: IL-3, GMCSF, PGE2 (down with NP); with=more Th2 skewing so increased ECP, IL5, IgE
what is a reed-sternberg cell?
B lymphocyte origin (derived from lymph node germinal center); no longer able to express antibodies
what is the genetic association of Burkitt lymphoma?
c-myc translocation at 8q24
what is type I cyroglobulinemia associated with?
plasma cell dyscrasia and multiple myeloma
what is type II cryoglobulinemia associated with?
hep C infection; also find RF+ in types II & III
what is the autoAb in primary adrenal failure? what labs would help you identify this disease?
auto Ab to CYP21A2 (necessary to make corisone); labs will show low aldosterone and elevated renin
what is the autoAb in Type Ia DM
anti-GAD65; may be generated in context of infections with coxsackie B4 and enterovirus; genetics DR3, DQ2, DR4, DQ8
most common cause of nephrotic syndrome in children?
minimal change disease; destruction of foot processes (podocytes); usually benign course with steroid treatment
most common cause of nephrotic syndrome in adults
membranous nephropathy; primary due to auto Ab against Phospholipase A2 receptor, or secondary to hep b, malaria, syphillis, cancer, drugs, SLE, environmental toxins. results in Ig deposits and complement activation; immunofluorescence of IgG and C3; podocyte effacement
PSGN clinical features
10-14 days after impetigo or strep pharyngitis; leads to nephritic syndrome; mostly seen in kids, but also diabetics, alcoholics and IV drug users; antigen-antibody complexes are deposited which activates complement; clinically may have positive ASO or anti DNAse B; low C3
what is the most common glomerulonephritis in the world?
IgA nephropathy; mostly presents with asymptomatic hematuria; IgA is not elevated, but may have elevated circulating polymeric IgA and complexes with IgA
most common cause of membranoproliferative glomerulonephritis?
mixed cryoglobulinemia due to Hep C
what is the Ab detected in anti-glomerular basement membrane disease (aka Goodpastures)?
Ab against a3 chain of type IV collagen
what disease processes are associated with pauci-immune GN?
Wegener's (granulomatosis polyangiitis), microscopic polyangiitis and eosinophilic granulomatosis polyangiitis (Churg-Strauss)
what are the abs against in pemphigus?
desmoglein 3 and 1; flaccid bullae formation; +Nicholsky; life-threatening skin loss
what are the abs directed against in bullous pemphigoid?
BP230 and BP180 (hemidesmosomes)
what is the genetic cause of familial mediterranean fever?
MEFV (AR), which codes for pyrin
what is the genetic cause of TRAPS?
what is the genetic cause of HyperIgD (aka mevalonate kinase deficiency)?
MVK (AR), involved in cholesterol and steroid synthesis
what is the genetic cause of CAPS (cryopyrin associated periodic syndromes)?
CIAS1 (AD); encodes NLRP3 gene that makes cryopyrin
what is the genetic cause of PAPA (pyogenic arthritis, pyogenic gangrenosum (sterile), acne)?
PSTPIP1 (AD) also known as CD2 binding protein 1 leads to prolonged inflammasome activation
what is the genetic cause of DIRA (deficiency of IL1 Receptor antagonist) aka deficiency of anakinra?
IL1RN (AR); leads to uninhibited activity of IL1
what is the genetic cause of PLAID (PLCy2 associated antibody deficiency and immune dysregulation)?
PLCy2 (AD), results in diminished signaling at physiologic temps (hypogamm), but enhanced signaling at subphsyiologic temps (cold urticaria)
clinical features of PFAPA
2-3 days of fever every 3-8 weeks on consistent schedule; apthous ulcers, pharyngitis, stomatitis, cervical lymphadenitis; patients generally outgrow
clinical features of MFM? Tx:
days of fever with variable frequency and associated with peritonitis, pleuritis, arthritis and erysepalas; 10% can be associated with amyloidosis (most serious complication); colcicine prophylaxis
clinical features of TRAPs?
weeks of fever; 10% associated with amyloidosis
clinical features of HIDs
fevers from 3-7 days with painful adenopathy; urticarial like lesions, arthralgias, abdominal pain; vaccine and stress and lead to flares; rare amyloidosis; it is thought that decrease in isoprenoids leads to overproduction of IL1B
what are 3 diseases that are considered CAPS?
NOMID/CINCA (most severe), muckle wells (moderate) and familial cold-induced autoinflammatory syndrome (mild); get urticarial rashes, fever, sensoneural hearing loss, arthritis, conjunctivitis, amyloidosis; with NOMID can see bone issues, dysmorphism, DD and leptomeningeal inflammation; treat all with IL-1 blockade
what are the clinical features of DIRA?
neonatal period present with multifocal osteomylelitis and other bone/periosteum issues; skin manifestations with pustulosis with neutrophilic predominance
what T cell infiltrative pattern might you expect on BAL of patient with sarcoid?
elevated CD4:CD8 ratio, unlike hypersensitivity pneumonitis