Serologic and genetic markers of celiac disease: a sequential study in the screening of first degree relatives.
OBJECTIVE
The prevalence of celiac disease (CD) among the relatives and the complications of an undiagnosed CD prompted us to identify a useful disease screening strategy.


METHODS
We studied 441 first degree relatives of 208 CD patients by immunoglobulin (Ig)A antiendomysium antibodies (EMA) and radioimmunoprecipitation assay (RIA) IgA antitransglutaminase autoantibodies (TGAA). Of these, 364 were typed for human leukocyte antigen-DRB1, -DQA1, and -DQB1 genes by the polymerase chain reaction sequence specific primers method. It was suggested to the autoantibody-positive subjects that they should undergo intestinal biopsy.


RESULTS
TGAA were positive in 46 of 439 relatives, EMA in 38; intestinal lesions related to CD were present in 40 subjects. We also found two immunodeficient fathers with duodenal villous atrophy. In three serology-positive subjects, permission for intestinal biopsy was refused; for another three serology-positive cases, duodenal mucosa was normal. Thus, the strict CD prevalence resulted 9.5%, the enlarged prevalence 10.9%. The DQ2/DQ8 heterodimers were carried in 231 of 364 subjects and in 38 of 40 biopsy-proven celiac patients. Three DQ2-positive parents became positive to the serology during a long-lasting follow-up.


CONCLUSIONS
On the basis of a carefully conducted study, CD prevalence in our series was seen as very high. These data suggest an accurate algorithm to select candidates for intestinal biopsy among CD high-risk subjects. First, an evaluation of the sensitive RIA TGAA and of total IgA (in IgA deficiency RIA IgG anti-tissue transglutaminase assay) should be performed. Then, an evaluation of the TGAA and the genetic study would be advisable 2 to 3 years later in negative subjects. Those carrying the DQ2/DQ8 heterodimers should continue the serologic follow-up; the others need a clinical follow-up.
Bonamico
Margherita
M
Department of Pediatrics, University of Rome La Sapienza, Viale Regina Elena 324, 00161 Rome, Italy. margherita.bonamico@uniroma1.it
Ferri
Mirella
M
Mariani
Paolo
P
Nenna
Raffaella
R
Thanasi
Enina
E
Luparia
Rita P L
RP
Picarelli
Antonio
A
Magliocca
Fabio M
FM
Mora
Barbara
B
Bardella
Maria Teresa
MT
Verrienti
Antonella
A
Fiore
Benedetta
B
Uccini
Stefania
S
Megiorni
Francesca
F
Mazzilli
Maria Cristina
MC
Tiberti
Claudio
C
D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000032:analysis*; D001706:Biopsy; D002446:Celiac Disease / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005190:Family; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005983:Glutens / Q000008:administration & dosage / Q000276:immunology; D006683:HLA-DQ Antigens / Q000032:analysis*; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis*; D007223:Infant; D007422:Intestines / Q000473:pathology; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011863:Radioimmunoassay / Q000379:methods; D012698:Serologic Tests
D001323:Autoantibodies; D005819:Genetic Markers; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D007070:Immunoglobulin A; D005983:Glutens