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Coeliac Disease Bible Class Questions and Answers Jan Hendrik Niess

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Coeliac Disease

Bible Class

Questions and Answers

Jan Hendrik Niess

What is the definition of coeliac disease?

What is the definition of non-coeliac gluten sensitivity (NCGS)?

Coeliac disease is an immune reaction to gluten (wheat, barely, rye) in an

genetic predisposed individual that results into an (small intestinal) enteropathy

- asymptomatic (subclinical) coeliac disease

- symptomatic coeliac disease

- refractory coeliac disease

- potential coeliac disease

Non-coeliac gluten sensitivity is a disorder, in which gluten intakes results in

clinical symptoms (no enteropathy, no elevated transglutaminase antibodies,

no change in permeability)

According to the Oslo classification gluten-intolerance, gluten-

sensitivity, silent coeliac disease should not be used

What is the worldwide prevalence of coeliac disease?

Prevalence (children) in Switzerland 1:132

Swiss Med. Wkly 2002;132:43-47

No CD in Burkina Faso

(low freqenecy of HLA DQ2 /DQ8 )

High incidence of CD in Finland,

Mexico, Algeria and North India

Why is there a difference in prevalence

of CD in Algeria and Tunisia?

(neighbouring countries, same gluten

Intake, same HLA DQ2 / DQ8 frequency)

What is the prevalence of coeliac disease in Switzerland?

Does the presence of HLA DQ2 / 8 alone explain the occurence of CD?

Although mucosal immunological

sensitization is an invariable feature of celiac

disease, it is not the precipitating factor for

the expression of the full intestinal lesion;

a second factor drives the enteropathy from

minimal (latent) to overt. . . Candidate factors

include an episode of hyperpermeability,

nutrient deficiency, increased dietary gluten,

impaired intraluminal digestion of ingested

gluten, adjuvant effects of intestinal infection

and a non-HLA associated gene.

Anne Ferguson

20-25% of the population are positive

for HLA DQ2/8

Annu Rev Immunol. 2011;29:493-525.

What are common symptoms of coeliac disease?

• Symptomatic malabsorption

• Diarrhea with weight loss

• Chronic diarrhoea with or without abdominal pain

• Chronic iron deficiency

• Metabolic bone disease; premature osteoporosis

• Unexplained weight loss

• Abnormal elevated liver enzymes

• Incidentally discovers villous atrophy

• Dermatitis herpetiformis

• Peripheral neuropathy

• Oral aphthous ulcers

• Growth failure

• Discoloured teeth or synchronous enamel loss

• Thyroid disease

• Down`s and Turner`s syndrome

• Type I diabetes

• Selective IgA deficiency

With what diseases is coeliac disease often associated?

How do you diagnose coeliac diases?

Serology (tissue transglutaminase IgA)

At least 6 biopsies ( bulb: 9 and 12 o‘clock position; 4 biopsies distal duodenum)

TTGA IgA 111 U/l ,

60 IEL /100 enterocytes

Marsh-Oberhuber Stadium 3b

Patient A. M. , 29/07/1940, referred to upper endoscopy, manifest osteoporosis

If there is a disagreement between serology and biopsy………

then HLA DQ2 and DQ8 genotyping

Consider selective IgA deficiency

Other reasons for villous atrophy

Marsh

modified

(Oberhuber)

Histologic criterion Corazza

Increased

intraepithelial

lymphocytesa

Crypt

hyperplasia

Villous

atrophy

Type 0 No No No None

Type 1 Yes No No Grade A

Type 2 Yes Yes No

Type 3a Yes Yes Yes (partial) Grade B1

Type 3b Yes Yes Yes (subtotal)

Type 3c Yes Yes Yes (total) Grade B2

a >40 intraepithelial lymphocytes per 100 enterocytes for Marsh modified (Oberhuber); >25 intraepithelial

lymphocytes per 100 enterocytes for Corazza.

How can the histological changes be classified?

What can cause villous atrophy?

• Tropical sprue

• Small bowel bacterial overgrowth

• Autoimmune enteropathy

• Drug-associated enteropathy (e.g. olmesartan)

• Whipple disease

• Eosinophilic enteritis

• Intestinal lymphoma

• Crohnn`s disease

• Graft versus host disease

• Malnutrition

• Acquired immune deficiency enteropathy

Why is HLADQ2 and DQ8 important?

Why is the tissue transglutaminase important?

Antigen Presenting Cell (APC)

CD4 T Cell

HLA DQ 2 or HLA DQ 8

Alpha / beta T Cell Receptor

Gluten

Proinflammatory cytokines IFNg, IL-21)

A B

Annu Rev Immunol. 2011;29:493-525.

Explain the patho-physiology of coeliac disease

Gluten intake

Presentation by HLA DQ2/8

Production of IL-15

Proliferation of the IEL

Blood. 2012 Mar 15;119(11):2458-68

Can you propose an animal model for coeliac disease?

x

HLA DQ8 IL-15tg

Gluten

+

Retinol

Proinflammatory cytokines

Breakdown of oral tolerance

wt

Gluten

+

Retinol

Tolerogenic immune response

Nature. 2011 Mar 10;471(7337):220-4

How do you treat coeliac disease?

Gluten-free diet (avoid wheat, rye, spelt, barely)

Follow up of patients with coeliac disease

Am J Gastroenterol. 2013 May;108(5):656-76

What do you consider if patients do not respond to gluten free diet?

• Gluten intake

• Bacterial overgrowth

• Microscopic colitis

• Exokrine pancreas insufficiency

• Fructose / Lactose intolerance

• Refractory coeliac disease

How is refractory coeliac disease defined?

Villous atrophy unresponsive to gluten-free diet (GFD)

How do you distinguish refractory coeliac disease type I and II?

Semin Immunopathol. 2012 Jul;34(4):601-13.

What is the importance to distinguish refractory coeliac disease

type I from II?

Blood. 2012 Mar 15;119(11):2458-68

Thank you