Serological assessment for celiac disease in IgA deficient adults.
OBJECTIVE
Selective immunoglobulin A deficiency is the most common primary immunodeficiency disorder that is strongly overrepresented among patients with celiac disease (CD). IgG antibodies against tissue transglutaminase (tTG) and deamidated gliadin peptides (DGP) serve as serological markers for CD in IgA deficient individuals, although the diagnostic value remains uncertain. The aim of this study was to investigate the prevalence of these markers in a large cohort of IgA deficient adults with confirmed or suspected CD and relate the findings to gluten free diet.


METHODS
Sera from 488,156 individuals were screened for CD in seven Swedish clinical immunology laboratories between 1998 and 2012. In total, 356 out of 1,414 identified IgA deficient adults agreed to participate in this study and were resampled. Forty-seven IgA deficient blood donors served as controls. Analyses of IgG antibodies against tTG and DGP as well as HLA typing were performed and a questionnaire was used to investigate adherence to gluten free diet. Available biopsy results were collected.


RESULTS
Out of the 356 IgA deficient resampled adults, 67 (18.8%) were positive for IgG anti-tTG and 79 (22.2%) for IgG anti-DGP, 54 had biopsy confirmed CD. Among the 47 IgA deficient blood donors, 4 (9%) were positive for IgG anti-tTG and 8 (17%) for anti-DGP. Four were diagnosed with biopsy verified CD, however, 2 of the patients were negative for all markers. Sixty-eight of 69 individuals with positive IgG anti-tTG were HLA-DQ2/DQ8 positive whereas 7 (18.9%) of the 37 individuals positive for IgG anti-DGP alone were not.


CONCLUSIONS
IgG anti-tTG seems to be a more reliable marker for CD in IgA deficient adults whereas the diagnostic specificity of anti-DGP appears to be lower. High levels of IgG antibodies against tTG and DGP were frequently found in IgA deficient adults despite adhering to gluten free diet.
Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden.
Ning
N
Wang
Department of Laboratory Medicine, Section of Microbiology, Immunology and Glycobiology, Lund University, Lund, Sweden.
Lennart
L
Truedsson
Department of Medicine, Clinical Immunology and Allergy Unit, Karolinska Institutet, Stockholm, Sweden.
Kerstin
K
Elvin
Department of Immunology, Sahlgrenska University Hospital, Gothenburg, Sweden.
Bengt A
BA
Andersson
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Johan
J
Rönnelid
Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
Lucia
L
Mincheva-Nilsson
Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden.
Annica
A
Lindkvist
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.
Jonas F
JF
Ludvigsson
Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden.
Lennart
L
Hammarström
Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
Charlotte
C
Dahle
D000328:Adult; D015415:Biomarkers / Q000097:blood; D002446:Celiac Disease / Q000097:blood* / Q000150:complications / Q000276:immunology; D005260:Female; D019204:GTP-Binding Proteins / Q000276:immunology*; D005903:Gliadin / Q000276:immunology*; D006801:Humans; D017098:IgA Deficiency / Q000097:blood* / Q000150:complications / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood* / Q000276:immunology; D008297:Male; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases / Q000276:immunology*
D015415:Biomarkers; D007074:Immunoglobulin G; D005903:Gliadin; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins