Administrative Office
St. Joseph's Hospital Site, L301-10
50 Charlton Avenue East
HAMILTON, Ontario, CANADA L8N 4A6
PHONE: (905) 521-6141
FAX: (905) 521-6142
http://www.fhs.mcmaster.ca/hrlmp/
Issue No. 42
QUARTERLY NEWSLETTER
Spring, 1996
THE SEROLOGIC DIAGNOSIS OF CELIAC DISEASE:
ANTIGLIADIN, ANTIRETICULIN AND
ANTIENDOMYSIAL ANTIBODIES
Clinical Features 1
The prevalence of Celiac disease (otherwise known as "Celiac sprue", "non-tropical sprue" or "glutensensitive enteropathy") is in the order of 1 in 1000 although this is probably an underestimate since a
number of affected individuals are asymptomatic. The incidence is highest in children aged 1-3 and presents
classically as diarrhea, growth retardation and anemia. Adolescents can present with delayed puberty and in
adults, anemia without other GI symptoms can be a prominent feature.
Cause and Pathogenesis
2
Small intestinal mucosal damage is caused by the fraction of wheat gluten containing gliadin polypeptides.
The mechanism by which this toxic reaction occurs in susceptible individuals is not known, but there is
strong evidence for an immune component. Thus the sera of affected individuals can contain antibodies
against gliadin and mucosal components which are usually not found in significant titers in normal
individuals, and these antibodies have proven to be useful for both the diagnosis and monitoring of celiac
disease. They are antigliadin (AGA) IgA and IgG, antireticulin (ARA) IgA and antiendomysial (EMA) IgA.
Diagnosis
The European Society of Pediatric Gastroenterology and Nutrition (ESPGAN) acknowledges the diagnostic
usefulness of "celiac antibodies" but states that a small intestinal biopsy is still needed to establish a positive
diagnosis.3 The following table includes data from several recent studies.
Sensitivity, Specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV) of the four
antibodies in the diagnosis of celiac disease
Sensitivity
(%)
Specificity
(%)
PPV
(%)
NPV
(%)
AGA IgG4
88
92
88
92
AGA IgA4
52
94
94
74
AGA IgG & 1gA5, 6
96-100
96-97
-
-
EMA IgA (age > 2)4
97
98
97
98
53-65
100
100
7177
99.6
99.3
99.3
99.6
ARA IgA4
AGA IgG, IgA, & EMA
IgA7
The IgG antigliadin antibody (AGA IgG) and the IgA antiendomysial antibody (EMA IgA) have both high
sensitivities and negative predictive values. AGA IgG, however, is found in normal individuals, individuals
with various autoimmune disorders, cow's milk protein intolerance, acute infectious diarrhea, chronic
intractable diarrhea, parasitosis, primary biliary cirrhosis and hepatitis C. 1 All three IgA species, AGA, ARA
and EMA have high specificities and positive predictive values, however they can be negative in patients
with selective IgA deficiency which is associated with celiac disease. Some clinicians recommend screening
with all four antibodies to achieve the highest sensitivity and specificity.
Who to Test
Anyone with a clinical picture suspicious for celiac disease should have serologic screening. Positive IgA
antibodies will usually return to normal within three months of the initiation of a gluten-free diet making them
useful for monitoring compliance and efficacy of treatment.2 Anyone with a positive AGA IgG but negative
IgA antibodies should be screened for selective IgA deficiency. Some authorities believe that first degree
relatives of patients with celiac disease should be screened serologically, because of the high prevalence of
asymptomatic celiac disease and the risk of GI lymphoma in untreated celiac patients. 1 As of yet there is no
strong evidence to support this practice.8
Sample Required and Turnaround Time
There is no patient preparation required. A minimum of 5 mL of whole blood should be collected in a redtopped tube and forwarded to the Clinical Immunology Laboratory at Chedoke-McMaster with a request for
"Celiac Antibody Profile". Samples will be processed on a biweekly basis. Results will be reported as
positive, negative or borderline and a written interpretation will be provided. When positive, a concentration
will be given and a titre will also be provided for the EMA IgA. For more information contact: B. Roberge,
Diagnostic Unit Manager, Regional Immunology Laboratory, Room 2N49, (905) 521-2100 Ext. 76267,
Chedoke-McMaster Hospitals.
Prepared by J. Cochrane, M.D.
Resident in Medical Biochemistry
Department of Pathology
McMaster University
References
1. Misra S, Ament ME: Diagnosis of coeliac sprue in 1994. Gastroenterol Clin of North Am 24(1):133-43,
1995
2. Trier JS: Celiac Sprue. New Engl J Med 325(24): 1709-19, 1991
3 Walker-Smith JA, Guandalini S, Schmitz J, Shmerling DH, Visakorpi JK: Revised criteria for diagnosis of
coeliac disease. Report of Working Group of European Society of Pediatric Gastroenterology and Nutrition.
Arch Dis Child 65: 909-91 1; 1990
4 . Lemer A, Kumar V, lancu TC: Immunological diagnosis of childhood coeliac disease: Comparison
between antigliadin, antireticulin and antiendomysial antibodies. Clin Exp Immunol 95:78-82; 1994
5 Goncri J, Skerritt IH, Mitchell ID: A reliable screening test for coeliac disease: enzyme-linked
immunosorbent assay to detect anti-gliadin antibodies in serum. Aust NZ J Med 21: 723-31, 1991
6. Burgin-Wolff A, Berger R, Gaze H, Huber H, Lentze MJ, Nussle D: IgG, IgA and IgE gliadin antibody
determinations as screening test for untreated coeliac disease in children, a multicentre study. fur ] Pediatr
148:496-502, 1989
7. Burgin-WolB Gaze H, Hadziselimovic F, Huber H, Lentze MJ, Nussle D, Reymond-Denhet C: Antigliadin
and antiendomysium antibody for coeliac disease Arch Dis Child 66:941-47. 1991
8. Howdle PD (ed): Coeliac Disease, Bllliere's Clin Gatroenterol 9(2), 1995
We are looking forward to providing further improvements in service, and welcome comments and enquiries.
Feel free to phone us at 521-5084, or 521-2100, extension 3710.
*********************
The Hamilton Health Sciences Laboratory Program is a collaborative program of Hamilton Civic, St.
Joseph's and Chedoke-McMaster Hospitals, which operate Community Laboratory Services as a service to
Hamilton Physicians and their patients.
For further information concerning the Laboratory Program call Mr. A.J. Bailey at 572-7575 and for
Community Laboratory Services telephone Mrs. K. Williams at 521-6052.
COMMUNITY LABORATORY SERVICES
Collection Centres
Ancaster Centre
226 Wilson Street E.
Ancaster, Ontario
Tel: (905) 648-4080
Charlton Centre
25 Charlton Ave. E.
Hamilton, Ontario
Tel: (905) 521-6052
George St. Centre
196 George St.
Hamilton, Ontario
Tel: (905) 525-1562
Carlisle Centre
1493 Centre Rd.
Carlisle, Ontario
Tel: (905) 689-0818
Dundas Centre
16 Cross St.
Dundas, Ont.
Tel: (905) 627-3814 or
(905) 627-7190
Concession Centre
688 Concession St.
Hamilton, Ontario
Tel: (905) 383-2021
First Place Centre
350 King St. E., Ste. 103
Hamilton, Ontario
Tel: (905) 522-8765/66
North Hamilton Centre
554 John St. North
Hamilton, Ontario
Tel: (905) 522-4197
Stoney Creek Centre
2757 King Street E.
Hamilton, Ontario
Tel: (905) 573-4824
Fennell Centre
836 Fennell Street E
Hamilton, Ontario
Tel: (905) 383-0505 or
(905) 383-9953
East Hamilton Centre
1463 Main St. East
Hamilton, Ontario
Tel: (905) 549-5004
For Housecalls
throughout the region,
telephone Mrs. K.
Williams at (905) 5216052
For Laboratory Reference Centre Services phone Mrs. B. Baltzer at (905) 521-6065 or fax requests for
information to (905) 528-1464