The natural history of gluten sensitivity: report of two new celiac disease patients resulting from a long-term follow-up of nonatrophic, first-degree relatives.
OBJECTIVE
Early studies revealed that up to 50% of non-atrophic, first-degree relatives of celiac disease patients exhibit features of gluten sensitivity. However, whether these features progress to a fully expressed celiac disease remain partially known. Our aim was to report two new patients resulting from a prospective, long-term surveillance of relatives who were nonatrophic at initial assessment.


METHODS
After a median time of 86 months (range: 42-102 months) from the baseline assessment, we re-evaluated 44 first-degree relatives of propositi who had taken part in family studies and in whom baseline small intestinal biopsies were normal. At the baseline screening, 21 relatives had positive serum antigliadin antibodies and/or increased intraepithelial lymphocyte infiltration, and 23 did not. In addition, 11 of 18 had a celiac-like response to rectal gluten challenge and 16 of 34 possessed the characteristic HLA DQ2 haplotype (DQA1 0501 DQB1 0201). Re-evaluation was based on celiac-related serology antigliadin (AGA) and endomysial (EmA) antibodies. EmA-positive subjects underwent intestinal biopsy.


RESULTS
At the end of the study, EmA was positive in only two subjects. Histological examination revealed flat small bowel mucosa in both. At baseline, both cases were EmA-negative and no minor histological changes were observed. One was a woman with positive baseline IgA and IgG AGA and a rectal gluten challenge with a celiac-like response; the other patient has presented only with a positive IgG AGA. In both cases, progression was detected in a clinically silent context. Both new patients had the characteristic HLA DQ2 haplotype.


CONCLUSIONS
Our data suggest the need to re-evaluate relatives who have been negative on initial screening for celiac disease. Up to now, the progression to severe enteropathy was only observed in relatives who had presented some evidence of gluten sensitivity and the characteristic HLA DQ2 haplotype. Longer longitudinal studies are necessary to obtain definitive conclusions.
Niveloni
S
S
Clinical Service, Hospital de Gastroenterología Dr. Carlos Bonorino Udaondo, and Universidad del Salvador, Buenos Aires, Argentina.
Pedreira
S
S
Sugai
E
E
Vazquez
H
H
Smecuol
E
E
Fiorini
A
A
Cabanne
A
A
Dezi
R
R
Valero
J
J
Kogan
Z
Z
Maurino
E
E
Bai
J C
JC
D000293:Adolescent; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000097:blood; D001706:Biopsy; D002446:Celiac Disease / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D018450:Disease Progression; D004848:Epithelium / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D005903:Gliadin / Q000276:immunology; D005983:Glutens / Q000009:adverse effects; D006683:HLA-DQ Antigens / Q000032:analysis / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007413:Intestinal Mucosa / Q000473:pathology; D007421:Intestine, Small / Q000473:pathology; D008137:Longitudinal Studies; D008214:Lymphocytes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009210:Myofibrils / Q000276:immunology; D011159:Population Surveillance; D011446:Prospective Studies
D000906:Antibodies; D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D005983:Glutens; D005903:Gliadin