Ch. 6 Immunologic Disorders Flashcards
what differentiates HAE type I from type II?
type II has normal or high C1 inh level
HAE with normal C1 inh is different from HAE I and II how?
later onset, more facial and tongue swelling, and associated with factor XII mutation
side effects of androgens for treatment of HAE?
hepatotoxicity, dysplipidemia, masculinization, headaches
what C1-inh for long term prophylaxis of HAE
cinryze
what plasma-derived C1 inh for acute attacks of HAE
berinert
what recombinant C1-inh for acute attacks of HAE?
Ruconest (caution in rabbit allergy)
what treatment for acute attacks has black box warning of anaphylaxis?
ecallantide (Kalbitor)
mechanism of action of ecallantide?
kallikrein inhibitor for acute attacks
mechanism of action of icatibant?
bradykinin receptor antagonist for acute attacks
what lab value distinguishes acquired angioedema from hereditary forms?
low C1q
acquired angioedema type 1 vs type 2
type 1: lymphoproliferative disorders, C1 inh level low due to consumption by neoplasm
type 2: autoAb to C1inh (C1 inh levels normal)
which cytokine receptors have the common gamma chain?
IL-2, 4, 7, 9, 15, and 21 receptors
which SCID is X-linked?
common gamma chain
common gamma chain and JAK3 deficiency have what lymphocyte phenotype?
T-B+NK-
difference is that JAK3 is aut. rec., common gamma chain is x-linked
IL-7Ra and IL-2Ra deficiency have what phenotype?
T-B+NK+
CD45 and CD3 deficiency have what lymphocyte phenotype?
T-B+NK+
RAG1/2 deficiency lymphocyte phenotype
T-B-NK+
NOT radiosensitive
presentation of Omen’s syndrome?
erythroderma, eosinophilia, high IgE, FTT, diarrhea
clinical findings in ADA deficiency?
skeletal abnormalities, rachitic rosary rib cage, deafness
lymphocyte phenotype in ADA deficiency
T-B-NK-
clinical findings in reticular dysgenesis?
severe neutropenia, sensorineural deafness, genetic defect: adenylate kinase 2 (AK2)
clinical findings in PNP deficiency?
lymphoreticular disease and autoimmune disease
what gene defects result in radiosensitive SCID
Artemis, Cernunnos, Ligase IV, and NBS1 (Nijmegen breakage syndrome)
Causes of CD8 lymphopenia
MHC I deficiency (TAP1/2 def, tapasin def), Zap70 def
Causes of CD4 lymphopenia
MCH II deficiency (bare lymphocyte syndrome), Lck def, HIV
ATM gene function
PI3 kinase responsible for DNA repair breaks, hence why radiosensitive
what lab finding is distinguishing/ unique in Ataxia telangiectasia
elevated AFP
CD40L and CD40 deficiency have similar presentations but different inheritance pattern how?
both have no germinal centers
CD40L = X-linked
CD40 = aut. rec
DiGeroge syndrome features
cardiac defects, abnormal facies, thymic hypoplasia, cleft palate, hypocalcemia, ch 22 defect (22q11.2 deletion)
X-linked hypomorphic mutation in NEMO clinical findings?
(ectodermal dysplasia with immunodeficiency) bacterial, opportunistic and mycobacterial infections, reduced sweat, ectodermal dysplasia, conical incisors, hypodontia, nail abnormality, hypotrichosis
LZ-NEMO mutation and what other mutation can result in mycobacterial infections due to poor production of IL-12 and IFNgamma
IFNGR1/2 deficiency
STAT 3 deficiency inheritance pattern and findings?
aut dominant
recurrent skin/lung abscesses/pneumatoceles, eczema, high IgE, mucocutaneous candidiasis, abnormal facies: prominent mandible, coarse features
DOCK 8 deficiency inheritance pattern and findings
aut recessive
severe viral skin infections (HPV, molluscum,etc), severe mucocutaneous candidiasis, eczema, allergies
NO SKELETAL/DENTAL abnormalities
IPEX mutation and inheritance pattern
X-linked, FoxP3 mutation
FTT, DM1, cytopenia, rash
XLP mutation?
SH2D1A gene encoding SAP
XLP features
EBV mononucleosis, HLH
Wiskott Aldrich syndrome features
thrombocytopenia + bleeding diathesis, eczema, recurrent infections
XLA mutation and features
Btk mutation (arrest at pre-B cell) enteroviral encephalitis, no germinal center, no lymph nodes
aut recessive agammaglobulinemia defects?
surrogate light chain (mu IgM heavy chain most common, lambda5, V pre-B) Ig alpha, Ig Beta, BLNK
what is Kabuki syndrome
mutation in KMT2D
hypogam, cleft palate, abnormal facies, developmental delay
CVID + thymoma is?
Good’s syndrome
red cell aplasia, neutropenia, chronic diarrhea
AID and UNG deficiency are hyperIgM syndromes but differ from CD40 and CD40L deficiency how?
giant germinal centers (lymphoid hyperplasia and adenopathy) and less severe infections in AID and UNG, absent germinal centers in CD40 and CD40L deficiency
what CD marker is defective in LAD1 and LAD2, respectively?
LAD1: CD18,
LAD2: CD15a (Sialyl-Lewis X)
WHIM syndrome features
sinopulmonary infection, papillomavirus warts, neutropenia but hyper cellular marrow (myeljkathexis)
WHIM mutation
aut dom, CXCR4
warts, hypogam, infection, myeljkathexis
severe congenital neutropenia mutations?
Kostmann syndrome (aut recessive, HAX 1) Elastase deficiency (aut dominant)
cyclic neutropenia lab findings
neutropenia, thrombocytopenia, dec monoctyes, reticulocytes in 21 day cycles, last 3-6 days
defect: ELANE
clinical features of LAD1
impaired pus formation, gingivitis, delayed wound healing, necrotic skin, infections (neutrophilia)
clinical features of LAD2
developmental delay, microcephaly, and short stature, Bombay phenotype
gene mutation in LAD2?
FUCT1 gene (no fucosylation) no Sialyl Lewis X (CD15a), defect in neutrophil rolling
gene mutation in LAD1?
ITGB2 gene mutation, common chain of B2 integrin family (CD18) - defect in adhesion
Note: CD18 binds to alpha chain LFA-1/CD11a, Mac-1/CD11b, P150,95/CD11c
clinical feature of LAD3?
LAD1 + bleeding diathesis
gene mutation in LAD3?
CaDAG-GEF1 ( failure of cytokine activation of integrins), abnormality of Rap GTPase function
genetic mutation in Chediak Higashi?
CHS1 gene, LYST protein
presentation of Chediak Higashi
oculocutaneous albinism, hypo pigmented skin, iris, hair, recurrent infections, neurologic defects, risk of HLH
appearance of neutrophils in Chediak Higashi?
enlarged lysosomal granules in neutrophils, neutropenia
what mutation in CGD is X-linked
p91 phox
what mutation in CGD is most common autosomal recessive
p47
what mutation in CGD is aut recessive and clinically similar to p91 phox
p22 (on membrane like p91 phox)
inheritance pattern of CGD can be determined by what test?
DHR fluorescence pattern via flow cytometry
IRAK 4 and MyD88 deficiency presentation
pyogenic bacterial infections, septicemia, liver abscess
Diseases that cause primary HLH
XLP, familial HLH, Chediak higashi, WAS
mutations in classical NK cell deficiency
GATA2 and MCM4
classical NK cell deficiency lab findings
low CD16, low NK function
functional NK cell deficiency lab findings
normal CD16, low NK function
mutations in functional NK cell deficiency
FCRG3A (CD16) mutation
CD16 is the low affinity IgG receptor
all complement deficiencies inherited in autosomal dominant manner except?
Properdin which is X-linked
clinical features and lab findings in C1q, C1s, C2, and C4 deficiency
sinopulmonary infections, SLE-like, low CH50
clinical features and lab findings in C3 deficiency
severe infections, glomerulonephritis, low CH50 and AH50, low C3, C3 nephritic factor, IgG anti-C3 autoab
MBL deficiency presentation
asymptomatic, can have autoimmune disease and respiratory infections (lab: low MBL, gene defect MASP2)
terminal complement deficiencies presentation
Neisseria infections (low CH50 and low AH50)
alternative pathway factor B, D, and properdin deficiency presentation and lab finding
Neisseria, low AH50
Which HIV type is more virulent and constitute the majority of HIV infections globally
HIV-1
which type is confined to West Africa
HIV-2
HIV proteins that are on the lipid bilayer membrane
gp120 and gp41
HIV nucleocapsid protein
p24
HIV outer membrane protein surrounding nucleocapsid
p17
which HIV protein binds to CD4 and CCR5 or CXCR4?
gp120
this will then induce a conformational change in gp41 resulting in HIV fusion with host cell membrane
what is the purpose of reverse transcriptase for HIV?
HIV ssRNA turned into dsDNA
integrase in HIV function
integrate dsDNA of HIV into host DNA
which coreceptor for HIV is M-tropic (monocytotropic)
CCR5
which coreceptor for HIV is T-tropic (T cell lymphotropic)
CXCR4
what allelic mutation confers resistance to CCR5 strain?
double-allelic CCR5delta32 mutation
what cells does HIV infect?
CD4+ T cells, macrophages, and dendritic cells
how does HIV attach to dendritic cells?
gp120 can bind to DC-SIGN
what is the most effective adaptive immune response to HIV during the acute phase?
cytotoxic T lymphocytes (CTLs)
what are the 3 mechanisms by which CD4+ T cell lymphopenia occurs?
direct viral killing of infected cells, apoptosis, and CTL killing of infected cells
CD4 T cell count that defines AIDS
CD4 <200 cells/mm3
initial test for HIV is ELISA, confirmatory test is by?
Western blot, requires 2 of 3 major bands: anti-p24, anti-gp41, anti-gp160/120
when 2 instances do you use HIV DNA PCR to detect HIV?
acute viral syndrome when Ab test is negative and in exposed infants
when do you use HIV RNA PCR?
quantify viral load
HIV p24 antigen testing is used for?
screening test with ELISA to detect infection sooner than ELISA alone; can also use in neonates or as marker of disease progression and response to treatment
how and when should HIV-1 exposed infants be tested?
via HIV-1 DNA PCR at birth within 14-21 days of age 1-2 months of age 4-6 months of age
at what age can you start using ELISA for HIV screening in exposed infants?
age 12-18 months, 18 months recommended
which HIV medication is a strong CYP3A4 and CYP2DG inhibitor that can increased ICS and intranasal corticosteroid levels leading to Cushings syndrome?
ritonavir
why should patients with a low CD4 count and opportunistic infections at the time of HIV diagnosis receive treatment to control the infection before HAART is initiated?
to minimize IRIS (immune reconstitution inflammatory syndrome) when the CD4 count rapidly increases and there is cytokine storm against the infection
medication for prophylaxis for PJP
TMP-SMX (CD4<200)
med for prophylaxis for Histo
itraconazole (CD4<150)
med for prophylaxis to Coccidioides
fluconazole (CD4<250)
med for prophylaxis to Mycobacterium avid complex
azithromycin, clarithromycin (CD4<50)
which mediator is implicated in EoE?
eotaxin-3
gene association studies have shown SNP variants in what mediator to be over expressed in EoE biopsy tissue?
TSLP
what pathologic features are seen on endoscopic exam of the esophagus?
strictures, mucosal rings, furrowing, ulceration, white plaques
PPI responsive esophageal eosinophilia features?
typical EoE symptom presentation, GERD excluded, and demonstrate clfinicopathologic response to PPIs
diagnosis of EoE?
> 15 eosinophils/hpf on biopsy after 8 weeks of PPI therapy
diagnostic criteria for HES?
> 1500 eosinophils, end organ dysfunction due to eosinophils, absence of other causes of eosinophilia
descending order of organ involvement at HES presentation?
derm > pulm > GI > cardiac > neurologic
common cause of death in HES
cardiac disease
acute necrosis, thrombus formation, then fibrosis
myeloproliferative HES is characterized by what lab features
finding of FIP1L1-PDGFRA mutation, elevated serum B12, elevated tryptase, cytopenia (anemia and thrombocytopenia)
lymphocytic HES characterized by what lab features
clonal TCR rearrangement, aberrant IL-5 producing T cells
what is Gleich syndrome
episodic angioedema with eosinophilia
myeloproliferative HES with FIP1L1-PDGFRA mutation can be treated with?
imatinib
must rule our or empirically treat what infection before starting systemic corticosteroids for HES?
Strongyloides - to avoid disseminated infection
When urticaria and erythema is observed on and around a macule after stroking the lesion
Darier’s sign
Which pediatric mastocytosis usually resolves without progression to systemic mastocytosis
diffuse cutaneous mastocytosis
Which CM (cutaneous mastocytosis) presents as discrete yellow brown macular-papular or nodular plaque like lesions with characteristic Darier’s sign
Urticaria pigmentosa
Which CM presents with diffuse yellow brown thickened skin, no discrete lesions, usually in patients <3 years of age
diffuse cutaneous mastocytosis
Which CM is a solitary reddish brown skin lesion that presents in the first 3 months of life and resolves spontaneously
Mastocytoma of skin
Which CM presents as macular telangiectasis characterized by increased mast cells around dilated capillaries and venues, typically in adults
Telangiectasia muscularis eruptiva perstans
what is the most common form of SM (systemic mastocytosis)
indolent systemic mastocytosis
what mutation leads to increased number of mast cells
KIT D816V - constitutive activation of KIT tyrosine kinase signaling
what is the ligand for c-KIT (CD117)
stem cell factor
mast cells are identified by what markers
CD117 (c-kit), coexpression of CD2 and/or CD25
diagnosis of CM?
focal dense mast cells infiltrates >15 mast cells per cluster or diffuse mast cell infiltrates >20 cells/hpf on skin biopsy; and c-KIT D816V mutation
diagnosis of SM?
1 major + 1 minor
3 minor
Major: biopsy with multifocal, dense mast cells >15 in aggregates
Minor:
- biopsy with more than 25% of mast cells having spindle shape or atypical morphology
- C-KIT D816V mutation
- expression of CD2 and/or CD25 on CD117+ mast cells
- total serum tryptase >20 ng/mL
diagnosis of mast cell activation syndrome
symptoms of mast cell activation but fail to meet WHO criteria for diagnosis of SM
diagnosis of monoclonal mast cell activation syndrome
presence of D816V mutation but does not meet WHO criteria for diagnosis of SM
treatment of mastocytosis
antihistamines, disodium cromoglycate, Epip, steroids, Gleevec (imatinib) in patients WITHOUT D816V, DEXA, Ca supplementation
what bacterias use the Ixodes scapularis as a vector?
Borrelia burgdorferi (Lyme), Anaplasma phagocytophilum (Anaplasmosis), Babes microti (Babesiosis)
How to diagnose Ehrlichiosis?
peripheral smear looking for intraleukocytic morulae
what vector does Ehrlichia chaffeensis use?
Amblyomma americium (Lone star tick)
How to diagnose Babesiosis?
microscopy and visualization of parasite on thin smear
diagnosis of early localized Lyme disease
clinical if erythema migrant present
diagnosis of early systemic and late systemic Lyme disease
serologic testing (ELISA + Western blot), PCR for either CSF (early) or synovial fluid (late)
Where is Lyme, Anaplasmosis, and Babesiosis endemic?
Northeast and Midwest
Where is Ehrlichiosis endemic
SE, south central, and mid-Atlantic region
IL-12 and IL-23 secretion by macrophages, monocytes, and dendritic cells stimulate naive T cells to differentiate into what type
Th1
IL-12 stimulate T cells to produce TNFalpha and IFNgamma via what transcription factor
STAT4
IFNgamma stimulates the production of IL-12 by macrophages and dendritic cells via what transcription factor?
STAT1
What anti-TNF medications can cause reactivation of latent TB
infliximab (anti-TNF ab), etanercept (TNFa receptor antibody)
Defects in IL-12/23-IFN-gamma pathway can lead to?
MSMD (Mendelian Susceptibility to Mycobacterial Diseases) and disseminated salmonella can be seen
increased mycobacterial infections are seen in these deficiencies
IL-12p40, IL-12RB1, IFNgR1, IFNgR2, STAT 1, STAT1 gain of function, NEMO (impaired CD40 dependent IL-12), TYK2 deficiency (AR hyper IgE), IRF8, GATA-2, ISG-15, CYBB
viral hepatitis pathogenesis and cell injury is due to?
HLA-restricted, virus specific CD8+ T cell lysis of infected hepatocytes and NK cells. Secretion of IFNg and TNFa results in injury
diagnosis of hepatitis A infection?
serology, IgM and IgG
what can be detected during the window period of Hep B infection and suggests an acute infection?
IgM HBcAb
the presence of what antigen indicates active Hep B liver disease, infectivity, and ongoing HBV DNA replication?
HbeAg
detection of what Ag after 6 months of acute HBV infection indicates chronic HBV?
HbsAg and IgG HBcAb
Vaccination of Hep B is denoted by what serologic findings
HBsAb ONLY
Carrier status of Hep B is denoted by what serologic findings
HBsAb and +/-HBsAg, low or normal HBV DNA
false positive nontreponemal tests occur in which 4 situations
pregnancy, IV drug use, endocarditis, and other infections: TB, nonsyphilis treponema, rickettsia, and HIV
false negative nontreponemal tests occur in what 2 situations
before formation of Ab to syphilis, or prozone reaction when very high antibody titers are present (needs dilution)
why are children younger than age 3 at increased risk of AOM?
lack of pneumococcal antibodies and because the horizontal position of the eustachian tub interferes with drainage
recurrent AOM is defined by
> 3 episodes within 6 months, or >4 episodes in 1 year with at least 1 episode in the last 6 months
in neonates, AOM may be caused by
Group B Strep
most common cause of AOM and acute bacterial rhinosinusitis
S. pneumo, H. influenza, M. catarrhalis
conjunctivitis with otitis is more likely caused by what organism
H.influenzae, needs augmentin
treatment of AOM if no recent (last 30 days) beta-lactam therapy, no concomitant purulent conjunctivitis, and no history of recurrent AOM?
high dose amoxicillin
treatment of AOM if there is recent beta-lactam therapy, or conjunctivitis, or recurrent AOM?
high dose amoxicillin-clavulanate
treatment of AOM if PCN allergic?
if Type I: macrolide or lincosamide
if delayed type: cefdinir, cefuroxime, cefpodoxime, ceftriaxone
leading cause of hearing loss in children
otitis media with effusion (OME)
complications of OME
hearing loss, TM retraction, or cholesteatoma
antibiotic treatment of choice for acute bacterial sinusitis?
amoxicillin-clavulanate
if PCN allergic, what abx for acute bacterial sinusitis in adults
respiratory fluoroquinolone or doxycycline
if PCN allergic, what abx for acute bacterial sinusitis in children
clindamycin + 3rd gen cephalosporin
recurrent sinusitis definition
> 4 episodes of ARS in 1 year
aspirin desensitization should be maintained on what dose?
650mg twice daily, once stable, then lower to 325mg twice daily
what are complications of sinusitis?
orbital cellulitis, subperiosteal abscess, cavernous sinus thrombosis, meningitis, subdural or epidural brain abscess, mucocele
CRS with nasal polyps have an increased incidence of?
anosmia, dust mite sensitization, asthma, AERD, and AFRS
CRS with NP have decreased quantity of which mediator
PGE2
recurrent pneumonia definition in children versus adults
children > or equal to 2 episodes in 1 year or 3 or greater episodes ever, in adults, >1 episode per decade
cryptogenic organizing pneumonia can be associated with what 3 disease processes
connective tissue disease, drugs, or malignancy
what is physical exam findings helps to distinguish bronchiolitis from viral induced wheezing
rales
most causes of croup are due to what virus?
parainfluenza
which virus is associated with more severe respiratory disease and in children with respiratory compromise
influenza A
in cases of respiratory distress a tracheal tube that is 0.5 to 1mm smaller should be used due to?
laryngeal edema
the presentation of croup differs in children and adults how?
children: barking cough
older children and adults: hoarseness
a PA CXR reveals what findings for croup?
“steeple sign” or subglottic narrowing
how does epiglottis present
no cough, neck extension protrusion, drooling, toxic appearance
“thumb sign” on lateral neck film
croup is diagnosed how?
clinical - barking cough, stridor
treatment of croup
nebulized epinephrine for rapid clinical improvement, single dose of IM dexamethasone for mild croup
what cells may be pathogenic in RA and other autoimmune disorders
Th17 cells
what cytokines do Th17 cells produce? and what is their function?
IL-17A, IL-17F, IL-22
recruit neutrophils and promote local innate immune defenses
what cytokines induce Th17 cells
IL-6 and TGF-B
survival of Th17 cells is enhanced by what cytokine
IL-23
what is RF?
antibody that binds Fc, usually IgM isotype
which autoAb is specific for RF and presence portends more aggressive disease
anti-CCP
JIA is divided into four subtypes, based on clinical and demographic factors, what are the subtypes?
pauciarticular, polyarticular, juvenile spondyloarthropathy, systemic onset (Still’s disease)
what is the most common type of JIA
pauciarticular
what HLA is associated with juvenile spondyloarthropathy
HLA-B27
what complement deficiencies are associated with SLE?
early complement: C1, C2, and C4 deficiency
what autoAb in SLE correlates with active disease and lupus nephritis
anti-dsDNA
what autoAb in SLE correlates with ILD?
anti-Smith
what autoAb is seen in neonatal lupus syndrome
Anti-Ro/La (congenital heart block, thrombocytopenia, annular rash)
what autoAb is seen in drug induced lupus
anti-histone
what autoAb is seen in recurrent blood clots and miscarriages
antiphospholipid
leading cause of mortality in SLE? presentation on lab and immunofluorescene?
lupus nephritis
UA - proteinuria, hematuria, casts, IF shows “full house” with IgG, IgA, IgM, C3, and C1q
treatment of lupus nephritis or CNS disease requires?
high dose corticosteroids, IV cyclophosphamide, cellcefpt, azathioprine, MTX, type I IFN
prognosis of SLE?
95% survival 5 yrs post diagnosis, 78% survival 20 years after diagnosis
presentation of neonatal lupus
heart block, photosensitive erythematous rash, elevated transaminases with hepatomegaly, cytopenias, hydrocephalus +/- macrocephaly
treatment of neonatal lupus cardiac manifetations
pacing for 3rd heart block, 1st and 2nd degree might respond to glucocorticoids
nearly all patients with drug induced lupus have what Ab?
ANA, and anti-histone (sensitive NOT specific)
drugs known to cause drug induced lupus
procainamide, quinidine, diltiazem, beta blockers, hydrazine, isoniazid, anti-TNF, ACE-i, penicillamine, minocycline, anticonvulsants, amiodarone
drug induced subacute cutaneous lupus is distinct from drug induced lupus how?
drug induced subacute cutaneous lupus has a photo-distributed rash and anti-Ro/SSA positive
sjogrens syndrome has increased risk of what?
lymphoma
autoAb in Sjogren’s
anti-Ro/SSA, anti-La/SSB
polymyositis/dermatomyositis is distinguished from myasthenia gravis by?
proximal muscle weakness, no distal muscle involvement or ocular involvement, sensation and reflexes are presernved
what autoAb in dermatomyositis
Anti-Jo-1 and Anti-M2 (associated with rash, good outcome)
polymyositis and inclusion body myositis is mediated by what cell type?
CD8+ T cells
dermatomyositis is mediated by?
Ab-mediated complement attack
CREST syndrome?
Calcinosis, Raynaud’s, esophageal dysmotility, sclerodactylyl, telangiectasias
ANA pattern in Scleroderma?
centromere or nucleolar
what autoAb is more common in diffuse systemic scleroderma? limited?
diffuse: Anti-Scl 70
limited: anti-centromere
treatment of scleroderma renal crises?
needs ACE-inhibitor
Hodgkin’s lymphoma pathology is characterized by the presence of?
Reed Sternberg cell
Burkitt’s lymphoma is associated with what infection and what gene?
EBV
c-myc gene translocation, at 8q24
MALTomas are associated with what infection?
H.Pylori
Splenic marginal zone B-cell lymphoma is associated with what infection?
Hep C
Sezary cells (mononuclear cells with a cerebriform nucleus) is commonly seen in what malignancy?
T cell lymphoma
Mycosis fungoides clinically presents with?
rash like plaques or patches, or generalized erythroderma
What is Sezary syndrome?
erythrodermic cutaneous T cell lymphoma with a leukemic involvement of malignant peripheral T-cell clones identical to those found in the skin lesions
Besides T cell lymphoma, Sezary cells can be seen in other malignancies and in the blood of healthy people, T or F?
True
what is the purpose of serum immunofixation in addition to doing electrophoresis for myelomas?
to ascertain the presence of an M protein and to determine its type
How is MGUS diagnosed?
<3g/dL of monoclonal paraprotein spike on SPEP, <10% of bone marrow involvement, no myeloma related organ or tissue impairment
diagnosis of multiple myeloma?
> 3g/dL monoclonal paraprotein spike on SPEP, >10% of clonal plasma cells on bone marrow biopsy, and evidence of myeloma-related organ or tissue impairment
4 symptoms of myeloma?
hypercalcemia, renal failure, anemia, bone lesions
diagnosis of Waldenstrom’s macroglobulinemia
SPEP showing M component with Beta to gamma mobility, the light chain of the monoclonal protein is usually the kappa light chain, bone marrow shows malignant cells
solitary plasmacytoma presentation?
pain at the site of skeletal lesions due to destruction of infiltrating plasma cells
What is POEMS syndrome?
A monoclonal plasma cell disorder with: Polyneuropathy, Organomegaly, Endocrinopathy (excluding DM or hypothyroidism), Monoclonal Protein, Skin Abnormalities
What is Castleman’s disease
giant cell lymph node hyperplasia, angiofollicular lymph node hyperplasia
what virus is implicated in the pathogenesis of Castleman’s disease
HHV-8
diagnosis of Cattleman’s disease?
monoclonal paraprotein spike on SPEP, staining of biopsy always shows lambda chain
what is heavy chain disease?
rare B-cell proliferative disorder where heavy chain cannot form disulfide bonds with the light chain, there are 3 types: alpha (most common), gamma and mu.
What are cryoglobulins?
single or mixed immunoglobulins that undergo reversible precipitation at low temperatures
which types of cryoglobulinemia contain RF that form complexes with the Fc portion of the polyclonal IgG?
type II and III
represent 80% of all cryoglobulins
The RF in Type II and III cryoglobulinemia differ how?
monoclonal RF in Type II
polyclonal RF in Type III
Type I cryoglobulinemia is associated with what cellular abnormality?
plasma cell dyscrasia and multiple myeloma
Type II and III cryoglobulinemia are associated with what infection?
Hep C
How long does it take Type I cryoglobulins to precipitate? type III?
I: 24 hrs
III: 7 days
acute hemolytic transfusion reactions are due to? presentation?
ABO-incompatible blood - IgM Ab:RBC Ag - fever, flank pain, red-brown urine
delayed hemolytic transfusion reactions are due to? presentation?
minor blood group Ag, Rh, Kell, Kidd, or Duffy blood groups - 5-10 days post transfusion with fever, jaundice
non-hemolytic febrile reactions are commonly seen after transfusion of what product?
platelets - due to cytokines TNFa and IL-1B - temp increase of more than 1 deg C.
how can one prevent non-hemolytic febrile reaction?
leukoreduction
urticarial reactions due to transfusions are most common in what type of transfusion?
FFP and platelet transfusion due to IgE against plasma proteins (prevent by washing blood products)
anaphylactic transfusion reactions often occur in which patients?
IgA deficient patients (anti-IgA Ab) - use twice washed RBCs or products from known IgA deficient donors
GVHD as a complication of transfusion can be prevented by?
gamma-irradiation of cellular blood products
When should TRALI be suspected and what is it caused by?
respiratory distress after 1-4 hours post-transfusion; donor leukocyte Ab are directed at recipient neutrophil Ag or HLA, C5a results in pulmonary leukosequestration of neutrophils
warm reactive AIHA is due to?
polyclonal IgG against RBCs
cold reactive AIHA is due to?
IgM binding to I antigen at T<37C
PNH is due to loss of what proteins on the surface of RBCs?
CD59 and CD55 (DAF)
PNH presents with?
hepatic vein thrombosis
how to prevent hemolytic disease of the newborn in RhD negative woman?
anti-D immunoglobulin at 28 weeks gestation and within 72 hours after delivery to prevent sensitization
what is Evans syndrome
ITP, AIHA without underlying etiology
Evans syndrome can be associated with what immune deficiencies?
CVID and ALPS
heparin induced thrombocytopenia is due to?
IgG Fab binds to complex between heparin and platelet factor 4, the IgG Fc binds to platelet FcIIa
TTP is due to autoAb against?
von Willbrand factor cleaving protease (ADAMTS13)
ALPS required criteria for diagnosis?
chronic >6 months nonmalignant, non infectious LAD or splenomegaly, elevated DNT cells
mutations associated with ALPS
Fas, FasL, Casp10
Graves is associated with what genetic alleles?
HLA-DR3 (whites), CTLA-4 alleles
What are Hurthle cells and what disease are they associated with?
epithelial cells enlarged with distinctive eosinophilic cytoplasm due to increased mitochrondria; Hashimoto’s thyroiditis
APS-2 is also known as Schmidt’s syndrome and endocrinopathy differs from APS-1 how?
APS 2: Adrenal>DM1>gonadal.
APS1 does not usually involve DM1 or the pituitary gland.
APS 1 is also known as APECED, what is the gene defect and presentation?
AIRE gene, hypoparathyroid>adrenal>gonadal>gut.
IPEX is due to mutation in what transcription factor?
FoxP3 mutation - depletion of Tregs
antibodies against what enzyme is found in Addison’s disease?
21-hydroxylase
diagnosis of Addisons?
ACTH stimulation, lack of serum cortisol rise
aldosterone and renin finding in primary adrenal failure ?
decreased aldosterone, increased renin
autoAb against what enzyme is found in primary adrenal failure
CYP21A2
Type IA diabetes has autoAb against? characterized by?
GAD65
low insulin and normal weight
genetics of Type IA diabetes
HLA-DR3,
DQ2 (DQA10501 and DQB10201)
DR4
DQ8 (DQA10301 and DQB10302)
most common nephrotic syndrome in children
minimal change disease
most common nephrotic syndrome in adults
membranous nephropathy
biopsy findings in membranous nephropathy
IF with granular staining of IgG and C3 along GBM. EM shows epithelial foot process effacement and sub epithelial deposits
when does post-streptococcal glomerulonephritis (PSGN) occur?
10-14 days after infection with group A hemolytic strep pharyngitis or impetigo
diagnosis of PSGN is clinical, however what laboratory findings can be seen in PSGN?
low C3, with evidence of circulating immune complexes, also can see +anti-ASO or anti-DNAse B, cryoglobulins, RF, high IgG
what is the most common glomerulonephritis in the world?
IgA nephropathy
clinical and laboratory features of IgA nephropathy?
asymptomatic microscopic or macroscopic hematuria, elevated circulating polymeric IgA and complexes of IgA in the serum
In which demographic and clinical scenario does Henoch Schonlein Purpura occur?
male predominance, children <10 years, following URI
most common cause of membranoproliferazive glomerulonephritis?
essential mixed cryoglobulinemia, associated with Hep C
What is Goodpasture’s syndrome
acute nephritis and pulmonary vasculitis with antibodies against alpha3 chain of type IV collagen
presentation of hemolytic uremic syndrome
hemolytic anemia, thrombocytopenia, and renal failure
what is the target antigens for pemphigus?
desmoglein 1, desmoglein 3
what is the target antigen for pemphigoid and linear IgA bulls dermatosis
BP 180, BP230
what is the target antigen for epidermolysis bulls acquisita
type VII collagen
how to distinguish episcleritis versus scleritis?
one drop of 10% phenylephrine will blanch episcleral redness within 20 minutes, but true scleritis will persist
what is pernicious anemia?
autoAb to parietal cell and intrinsic factor resulting in B12 malabsorption, macrocytic anemia, and neurologic symptoms
genetic association with celiac disease?
HLA-DQ2
test of choice for celiac disease?
IgA TTG high sensitivity and specificity
what condition can lead to false negative results in IgA TTG?
IgA deficiency
what autoAb are found in type I autoimmune hepatitis?
anti-smooth muscle, anti-actin, anti-soluble liver or pancreas Ag
what autoAb are found in type II autoimmune hepatitis?
anti-liver-kidney-microsomes-1 (ALKM-1), anti-liver-cytosol antigen (ALC-1 or LC1)
what genetic HLA and autoAb is associated with PBC?
HLA-A*0201, anti-mitochondrial Ab
what autoAb is seen in PSC?
anti-smooth muscle Ab
what gene mutation is associated with Crohn’s disease
NOD2/CARD15
Unlike UC, Crohn’s disease involves all regions of the GI tract and is characterized by what histopathology
noncaseating granulomas, skip lesions, transmural involvement
how does GB present?
paralysis that starts peripherally and is symmetrical
what autoAb is seen in MG?
anti-AchR
MG is associated with what conditions?
thymoma/thymic hyperplasia
what treatment is approved for MS (multiple sclerosis?)
Fingolimod, a sphingosine-1-phosphate receptor modulator
what autoAb is seen in Stiff person syndrome as well as DM I?
anti-GAD (100-500x greater than in type I DM)
