Senasta forskningsrön i celiaki

Transcription

1 Senasta forskningsrön i celiaki Markku Mäki Tammerfors Universitet och Universitetssjukhuset i Tammerfors, Tammerfors,, Finland Tammerfors

2 Classical presentations of coeliac disease

3 Coeliac disease Daily ingested wheat, rye, and barley induced manifest mucosal lesion in genetically susceptible individuals (DQ2 +ve or DQ8 +ve) gluten on off Clinically silent coeliac disease manifest mucosal lesion Gastrointestinal symptoms mild severe Symptoms and signs of malabsoption Risk groups Type I diabetes Thyroid disease Sjögren s syndrome Down s syndrome IgA deficiency Extraintestinal manifestations dermatitis herpetiformis, osteopenia and osteoporosis, dental enamel defects, peripheral and central nervous system invovement, liver diseases, reproductive system involvement, malignancies

4 Diagnosis of coeliac disease High index of suspicion Classical symptoms and signs Minor symptoms Extraintestinal manifestations Biopsy Antibody case finding Risk groups EMA ttg ab AGA (deamin peptide) whole blood rapid test

5 Membership development during in the Finnish Coeliac Society Membership development during /2006 in the Finnish Coeliac Associations /2006

6 Blood sampling in 1994 Schoolchildren n=3,654 Mäki et al., NEJM 2003 Serum autoantibody testing in 2001 IgA EMA+ IgA ttg+ n=50 n=1 n= 2 n=3 EMA and/or ttg + n=56 IgA EMA+ IgA ttg IgA EMA IgA ttg+ IgA EMA, IgG EMA + IgA ttg, IgG ttg+ Symptom detected CD Screen detected CD Normal on biopsy Not biopsied Smallbowel biopsies n=10 IgA EMA and ttg+ n=9 n=27 IgA EMA and ttg+ n=25 n=9 IgA EMA+ n=7 IgA ttg+ n=9 n=10 IgA EMA+ n=10 IgA ttg+ n=9 IgG EMA and ttg+ IgG EMA and ttg+ n=1 n=2 HLA DQ2+ n=7 DQ8+ n=3 DQ2+ n=22 DQ8+ n=3 DQ2/DQ8+ n=1 DQ2 and DQ8 n=1 DQ2+ n=7 DQ2/DQ8+ n=1 DQ2 and DQ8 n=1 DQ2+ n=10 Biopsy proven CD 1:99 Celiac trait 1:67

7 Mini Finland Health Clinical prevalence of CD 0.03% 0.52% Total prevalence of CD 1.1% 2.0% 95 % CI Lohi et al., Aliment Pharm Therap, 2007;26:

8 CD Type 1 DM Lohi et al., Aliment Pharm Therap, 2007;26:

9 Prevalence of coeliac disease in Finland CHILDREN 1.5 % ADULTS 2.0 %

10 Lower economic status and inferior hygienic environment may protect against celiac disease Kondrashova et al. Ann Med 2007, ifirst Article, 1 9 (epub ahead of print) Finland 1:100 Russian Karelia 1:500

11 Do DIY health tests work? We ask the experts for their verdicts. Unable to get an appointment with your GP? Too embarrassed by your symptoms? It's not surprising many of us now turn to home testing kits to diagnose potential problems. Daily Mail 24 Hours Per Day Nov 25, 2007

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14 Finger tip whole blood assay for coeliac disease, a new rapid point of care test Mäki M, Korponay Szabo I. Methods and means for detecting gluteninduced diseases 2001, IPN WO02/ A19 Korponay Szabó et al., Coeliac disease case finding and diet monitoring by point of care testing. Aliment Pharmacol Ther, 2005;22: Raivio et al., Self transglutaminase based rapid coeliac disease antibody detection by a lateral flow method. Aliment Pharmacol Ther 2006;24: Sensitivity and specificity = EMA, ttg ab

15 TG Principle of self TG based rapid antibody detection Haemolysis TG Label (anti IgA) TG Formation of self TG/anti /anti TG complexes TG Capture to solid surface TEST RESULT (5 min) +

16 Alliance apoteket, Norge Apoteksbolaget, Sverige

17 Biocard Celiac Test Rapid whole blood tests for coeliac disease, on site testing from finger tip capillary blood Sensitive and specific test (=EMA, TG2 ab) to detect untreated even clinically silent coeliac disease, meant for case finding, screening of risk groups and population based screenings No recombinant / purified TG2 antigen is needed Used in doctors offices No need for laboratory, the test is performed on site, no laboratory equipment needed, result available in 1 51 minutes. CE marked for home testing, available in pharmacies Use at home: Screening of family members, treatment follow up, might I have coeliac disease? Indications same as for EMA and ttg ab ab,, biopsy is so far needed for final diagnosis Immediate availability of results may help physicians to speed up the diagnostic process and to evaluate dietary compliance

18 Morphology of normal and coeliacc disease affected small bowel mucosa

19 Predictors for forthcoming CD Mild enteropathy coeliac disease Mucosal IgAdeposits Serum autoantibodies Mucosal villous tip IELs Mucosal γδ IELs Mucosal IELs (Marsh 1) HLA DQ2 or DQ8 Sens % Spesif % Salmi et al., Aliment Pharmacol Ther, 2006

20 Coeliac disease beyond villous atrophy Kaukinen et al., Gut 2007

21 Heavily underdiagnosed worldwide, diagnostic delay North America, South America, Europe, Arabic states India, others (not in Japanese, black Africans) Finland 1:50 UK 1:100 Many countries 1:100 1:200 Tools available for screening and rapid diagnosis Treatment available, but how to find, diagnose, and treat Cost benefit issues Life long gluten free diet novel therapies Genetic susceptibility The Coeliac Disease Iceberg DR3 DQ2, DR5/7 DQ2 DR4 DQ8 Clinical coeliac disease Silent coeliac disease Coeliac disease latency Healthy individuals Manifest mucosal lesion Normal mucosal morphology Mäki M. & Collin P. Lancet 1997;349: Jejunal morphology

22 Celiakipiller på kommande, forskning och kliniska studier på gång Normal slemhinna Glutenframkallad slemhinnaskada GLUTEN HINDRAR LÄKEMEDLET SLEMHINNASKADAN?

23 The sooner we are ready to meet the future, the longer we are able to stay there (Ralph Gothoni 1998)