POCT in celliac diseases.pdf
-
Upload
trinhthien -
Category
Documents
-
view
239 -
download
1
Transcript of POCT in celliac diseases.pdf
![Page 1: POCT in celliac diseases.pdf](https://reader034.fdocuments.net/reader034/viewer/2022051507/58a034a61a28abad4d8bd084/html5/thumbnails/1.jpg)
Use of POCT in celiac disease
Jernej Dolinšek, MD, PhD
Department of Pediatrics
Gastroenterology unit
University Medical Centre Maribor, Slovenia
Dubrovnik, 19. 10. 2013
![Page 2: POCT in celliac diseases.pdf](https://reader034.fdocuments.net/reader034/viewer/2022051507/58a034a61a28abad4d8bd084/html5/thumbnails/2.jpg)
2
• definition
• background
• diagnostic algorythms
• diagnostic tools
• use of POCT
• conclusions
Overview
![Page 3: POCT in celliac diseases.pdf](https://reader034.fdocuments.net/reader034/viewer/2022051507/58a034a61a28abad4d8bd084/html5/thumbnails/3.jpg)
3
Celiac disease is an autoimmune systemic
disease (disorder) triggered by the ingestion of
gluten in genetically predisposed subjects.
The disease is characterized by the production of
disease specific antibodies, which disappear
after introduction of a gluten-free diet (GFD).
All patients must comply with life-long strict
GFD.
Celiac disease – definition
![Page 4: POCT in celliac diseases.pdf](https://reader034.fdocuments.net/reader034/viewer/2022051507/58a034a61a28abad4d8bd084/html5/thumbnails/4.jpg)
“nature does nothing uselessly “
Aristotle
![Page 5: POCT in celliac diseases.pdf](https://reader034.fdocuments.net/reader034/viewer/2022051507/58a034a61a28abad4d8bd084/html5/thumbnails/5.jpg)
Celiac disease – immunology
Green P and Cellier C. N Engl J Med 2007.
![Page 6: POCT in celliac diseases.pdf](https://reader034.fdocuments.net/reader034/viewer/2022051507/58a034a61a28abad4d8bd084/html5/thumbnails/6.jpg)
undiagnosed vs. diagnosed CD (5-13):1
Incidence of symptomatic disease in NE Slovenia in 2009
1/452
Celiac disease – epidemiology
![Page 7: POCT in celliac diseases.pdf](https://reader034.fdocuments.net/reader034/viewer/2022051507/58a034a61a28abad4d8bd084/html5/thumbnails/7.jpg)
enamel defects
DH
celiac disease
epilepsy and cerebral
calcifications
autoimmune
diseases
liver disease
lymphoma
osteopenia
ataxia
DR3, DQ2 DR4, DQ8
GLUTEN
Clinical presentation of “celiac disease”
![Page 8: POCT in celliac diseases.pdf](https://reader034.fdocuments.net/reader034/viewer/2022051507/58a034a61a28abad4d8bd084/html5/thumbnails/8.jpg)
• History and physical exam
– Symptomatic CD
• Gastrointestinal disease
– Prolonged diarrhea
– Abdominal distension
– Failure to thrive, weight loss
• Extra-gastrointestinal disease
– Asymptomatic CD
Celiac disease – diagnostic approach
![Page 9: POCT in celliac diseases.pdf](https://reader034.fdocuments.net/reader034/viewer/2022051507/58a034a61a28abad4d8bd084/html5/thumbnails/9.jpg)
• Serology
• Genetics
• Intestinal biopsy
A
B
DQ5 DQ2
1 2 3 4 5 6 7 8
Celiac disease – diagnostic approach
![Page 10: POCT in celliac diseases.pdf](https://reader034.fdocuments.net/reader034/viewer/2022051507/58a034a61a28abad4d8bd084/html5/thumbnails/10.jpg)
Celiac disease – new diagnostic criteria
![Page 11: POCT in celliac diseases.pdf](https://reader034.fdocuments.net/reader034/viewer/2022051507/58a034a61a28abad4d8bd084/html5/thumbnails/11.jpg)
Diagnostic delays
duration of symptoms before dg
• adults 11 years
• children1.3 years
• large regional differences
Celiac disease – reality
![Page 12: POCT in celliac diseases.pdf](https://reader034.fdocuments.net/reader034/viewer/2022051507/58a034a61a28abad4d8bd084/html5/thumbnails/12.jpg)
Celiac disease – diagnostic tools
![Page 13: POCT in celliac diseases.pdf](https://reader034.fdocuments.net/reader034/viewer/2022051507/58a034a61a28abad4d8bd084/html5/thumbnails/13.jpg)
• disease specific tools
• serological tests
• genetic tests
• biopsy/histology
• nonspecific tools
• clinical picture
• tests of malabsorption
• …
Celiac disease – diagnostic tools
![Page 14: POCT in celliac diseases.pdf](https://reader034.fdocuments.net/reader034/viewer/2022051507/58a034a61a28abad4d8bd084/html5/thumbnails/14.jpg)
Celiac disease – serology
![Page 15: POCT in celliac diseases.pdf](https://reader034.fdocuments.net/reader034/viewer/2022051507/58a034a61a28abad4d8bd084/html5/thumbnails/15.jpg)
• Serological markers
• AGA IgA and IgG
• markers of autoimmunity
• EMA IgA (IgG)
• t-TG IgA (IgG)
• DGP IgA (IgG)
• other Ab (ARA, JAB, antiglutenin)
• importance of total IgA determination
• IgA deficiency – IgG Ab determination
Celiac disease – serology
![Page 16: POCT in celliac diseases.pdf](https://reader034.fdocuments.net/reader034/viewer/2022051507/58a034a61a28abad4d8bd084/html5/thumbnails/16.jpg)
Untreated On diet for 6 months
Celiac disease – serology
• tissue transglutaminase Ab
![Page 17: POCT in celliac diseases.pdf](https://reader034.fdocuments.net/reader034/viewer/2022051507/58a034a61a28abad4d8bd084/html5/thumbnails/17.jpg)
Celiac disease – genetic testing
![Page 18: POCT in celliac diseases.pdf](https://reader034.fdocuments.net/reader034/viewer/2022051507/58a034a61a28abad4d8bd084/html5/thumbnails/18.jpg)
• histological changes – intestinal biopsy
• aspiration capsule
• endoscopic biopsy
Celiac disease – histology
![Page 19: POCT in celliac diseases.pdf](https://reader034.fdocuments.net/reader034/viewer/2022051507/58a034a61a28abad4d8bd084/html5/thumbnails/19.jpg)
• Histological changes
• mucosal atrophy
• Marsh classification
• type 0: preinfiltrative phase
• type 1: infiltrative phase
• type 2: infiltrative-hyperplastic phase
• type 3 (a, b, c): destructive phase
• type 4: atrophic-hypoplastc phase
• villous atrophy, crypt hyperplasia, IEL count
Marsh MN. Gastroenterology 1992.
Oberhuber G et al. Eur J Gastroenterol Hepatol 1999.
Celiac disease – histology
![Page 20: POCT in celliac diseases.pdf](https://reader034.fdocuments.net/reader034/viewer/2022051507/58a034a61a28abad4d8bd084/html5/thumbnails/20.jpg)
Celiac disease – histology
![Page 21: POCT in celliac diseases.pdf](https://reader034.fdocuments.net/reader034/viewer/2022051507/58a034a61a28abad4d8bd084/html5/thumbnails/21.jpg)
Celiac disease – histology
![Page 22: POCT in celliac diseases.pdf](https://reader034.fdocuments.net/reader034/viewer/2022051507/58a034a61a28abad4d8bd084/html5/thumbnails/22.jpg)
• PoC tests
• rapid finger prick test
• immunochromatography
• antigen: self t-TG
• many commercial kits
• inexpensive
• intermediate sensitivity and specificity
Celiac disease – serology - POCT
Korponay-Szabo I et al. BMJ 2007; Dolinsek J et al. ICDS 2011.
Anti-IgA antibody
(Control line)
![Page 23: POCT in celliac diseases.pdf](https://reader034.fdocuments.net/reader034/viewer/2022051507/58a034a61a28abad4d8bd084/html5/thumbnails/23.jpg)
23
Celiac disease – POCT market
![Page 24: POCT in celliac diseases.pdf](https://reader034.fdocuments.net/reader034/viewer/2022051507/58a034a61a28abad4d8bd084/html5/thumbnails/24.jpg)
24
Company Brand Sample Parameters
Ani Biotech BioCard Whole blood Anti-tTG (IgA), Total IgA
Augurix Sintomax Whole blood Anti-DGP (IgA &IgG), Total IgA
Eurospital
XeliacTest Whole blood Anti-tTG (IgA & IgG)
Eu-tTG Screen
CD Screen Serum
Anti-tTG (IgA & IgG)
Anti-tTG / Gliad IgA
Operon
Simple CD1WB
Stick CD1
Whole blood
Serum Anti-tTG (IgA & IgG)
Simple CD2WB
Stick CD2
Whole blood
Serum Anti-tTG / Gliad IgA
Celiac disease – POCT market
![Page 25: POCT in celliac diseases.pdf](https://reader034.fdocuments.net/reader034/viewer/2022051507/58a034a61a28abad4d8bd084/html5/thumbnails/25.jpg)
25
Positive Result
Negative Result
Invalid Result
Handle
Reading area
Reaction area
Sampling area
Celiac disease – stick assay - serum
![Page 26: POCT in celliac diseases.pdf](https://reader034.fdocuments.net/reader034/viewer/2022051507/58a034a61a28abad4d8bd084/html5/thumbnails/26.jpg)
26
Reading window Sample
Positive Result Invalid Result
Celiac disease – cassete – whole blood
Negative Result
![Page 27: POCT in celliac diseases.pdf](https://reader034.fdocuments.net/reader034/viewer/2022051507/58a034a61a28abad4d8bd084/html5/thumbnails/27.jpg)
27
Celiac disease – POCT interpretation
![Page 28: POCT in celliac diseases.pdf](https://reader034.fdocuments.net/reader034/viewer/2022051507/58a034a61a28abad4d8bd084/html5/thumbnails/28.jpg)
• A negative result with an IgA-based assay may
occur due to total serum IgA deficiency and
lead to a doubtful interpretation of the result.
• Two options to offset total serum IgA
deficiency:
• Simultaneous detection of both class IgA and IgG
antibodies
• Detection of total serum IgA
• In same cases, total serum IgA deficiency is indicated by
the absence of both Test and Control lines.
• The same may occur when a test is not performed
properly.
28
Celiac disease – POCT in IgA deficiency
![Page 29: POCT in celliac diseases.pdf](https://reader034.fdocuments.net/reader034/viewer/2022051507/58a034a61a28abad4d8bd084/html5/thumbnails/29.jpg)
29
Sens. Spec. PPV NPV
Diagnosis 5 min 82.9% 93.6% 78.0% 97.7%
10 min 96.9% 89.5% 54.3% 99.1%
Dolinsek et al. 2012
Celiac disease – POCT performance
Anti-tTG CD Healthy
Pos Neg
Whole blood Pos 117 7 124
Neg 4 100 104
Total 121 107 228
Sens. 96.7% PPV 94.4%
Spec. 93.5% NPV 96.2%
Raivio et al. 2006
Anti-tTG CD Healthy
Pos Neg
Whole blood Pos 110 7 117
Neg 4 208 212
Total 114 215 329
Sens. 96.5% PPV 94.0%
Spec. 96.7% NPV 98.1%
Nemec et al. 2006
![Page 30: POCT in celliac diseases.pdf](https://reader034.fdocuments.net/reader034/viewer/2022051507/58a034a61a28abad4d8bd084/html5/thumbnails/30.jpg)
• Use of POC tests for GFD follow-up is still
under evaluation.
• Some studies confirm their use for monitoring
the compliance with the diet.
• On the other hand, a qualitative response does
not provide an indication of the antibody level,
which is important to check a diet adherence.
Celiac disease – POCT performance in GFD
![Page 31: POCT in celliac diseases.pdf](https://reader034.fdocuments.net/reader034/viewer/2022051507/58a034a61a28abad4d8bd084/html5/thumbnails/31.jpg)
• New microsystems
• finger prick blood, 30 minutes
• simultaneous
• multiple Ab test
• t-TG, DGP (IgA, IgG)
• total IgA determination
• HLA-DQ2/DQ8 status
Future perspectives
http://www.etseq.urv.es/cdmedics/index.php
![Page 32: POCT in celliac diseases.pdf](https://reader034.fdocuments.net/reader034/viewer/2022051507/58a034a61a28abad4d8bd084/html5/thumbnails/32.jpg)
• Celiac disease is important health problem
• diagnostic tools are reliable, but invasive
• POCT tests available
• high NPV, satisfactory PPV
• possibilty of use in developing regions
• limitations
• qualitative
• not diagnostic (not included in recommendations)
• possibilty of false negative results in IgA deficiency
• GFD monitoring
• new promising tools appearing
Conclusions
![Page 33: POCT in celliac diseases.pdf](https://reader034.fdocuments.net/reader034/viewer/2022051507/58a034a61a28abad4d8bd084/html5/thumbnails/33.jpg)
Conclusions
![Page 34: POCT in celliac diseases.pdf](https://reader034.fdocuments.net/reader034/viewer/2022051507/58a034a61a28abad4d8bd084/html5/thumbnails/34.jpg)