celiac disease

Question 1

2 necessary triggers for CD

Answer 1

genetics, gluten

Question 2

risk factors for CD (6)

Answer 2

• female
• bottle fed
• born by C-section
• born in summer
• higher SES
• certain viral/parasitic infections

Question 3

strong HLA class II assoc with:

Answer 3

HLA-DQ2(90-95%)

others HLA-DQ8

Question 4

why is the HLA assoc necessary but not sufficient for diagnosis?

Answer 4

although must have DQ2 or DQ8 for dx, many people have them and do not have disease (only 4% with those haplotypes have CD); but absence of these = exclusion of dx

Question 5

why is gluten resistant to digestion?

Answer 5

high content of proline (15%) and glutamine (35%)

Question 6

MOA of TTG

Answer 6

modification of gliadin epitodes- deamidates glutamine to form glutamic acid; glutamic acid then binds MHC-II with higher affinity

Question 7

action of IL-15

Answer 7

up-regulates expression of NK receptors of IELs

Question 8

2 changes in IECs seen in CD

Answer 8

• increased IELs (90% CD8) *hallmark

- increased gd T cells

Question 9

3 mucosal alterations seen in CD

Answer 9

• loss of epithelial cells
• proliferation of crypt epithelial cells
• atrophy of villi

Question 10

blood test for CD looks for

Answer 10

IgA against TTG

Question 11

what is the CD4 phenotype of gliadin-secific T cells? consequence?

Answer 11

TH1

secrete high amounts of IFNg

Question 12

what increases gut permeability to to gluten?

Answer 12

up-regulation of zonulin

Question 13

MOA of zonulin (4)

Answer 13

• activates PLC = DAG and IP3
• DAG and IP3 will activate protein kinase C
• PKC will phosphorylate target proteins to cause the polymerization of soluble G actin/F actin
• polymerization cause rearrangement of the filaments and displacement of proteins from the junctional complex leading to loosening of tight junctions

Question 14

humoral response in CD (3)

Answer 14

• AGA
• EMA
• anti-TTG

Question 15

cell mediated response in CD

Answer 15

activation of CD8 and CD4

Question 16

cytokine response in CD

Answer 16

IL-2
IL-15
IL-21
IFNg

Question 17

silent celiac

Answer 17

meet dx criteria but are asymptomatic, found on screening of high risk populations (DM1)

Question 18

potential celiac

Answer 18

have characteristic antibodies but lack mucosal sx

Question 19

latent celiac

Answer 19

at one point, met dx criteria but now do not

rare

Question 20

extrainestinal sx of CD (4)

Answer 20

rash
anemia
bone disease
elevated LFTs

Question 21

which populations should be screened for CD due to higher risk?

Answer 21

genetic d/o
autoimmune d/o
close relative with CD

Question 22

what sx are young children likely to present with in CD?

Answer 22

typical GI sx

Question 23

which pts are more likely to have an atypical presentation?

Answer 23

older than 5

Question 24

dermatitis herpetiformis

Answer 24

form of atypical presentation
erythematous macules/urticarial papules/vesicles
itchy
symmetric

Question 25

only instance that CD is dx without biopsy

Answer 25

dermatitis herpetiformis + positive serology

Question 26

why treat pt with silent CD?

Answer 26

still at risk for complications

Question 27

rare but serious complication of CD

Answer 27

enteropathy assoc T cell lymphoma

Question 28

4 roles of serology

Answer 28

- identify pts with sx that need bx - screen high risk asympt pts - evidence for dx - monitor adherence to diet

Question 29

when can serologies be falsely negative?

Answer 29

IgA deficiency, would need to do IgG testing

Question 30

which serologic test has the highest sensitivity? specificity?

Answer 30

sensitivity- anti-TTG | specificity- antiendomysial antibodies (EMA)