Cytokine genotyping (TNF and IL-10) in patients with celiac disease and selective IgA deficiency.
OBJECTIVE
Selective IgA deficiency (IgAD) and celiac disease (CD) are frequently associated and share the ancestral haplotype human leukocyte antigen (HLA)-8.1, which is characterized by a peculiar cytokine profile. The aim of this study was to evaluate the role of tumor necrosis factor (TNF) and interleukin (IL)-10 alleles in CD and CD-IgAD.


METHODS
The distribution of some biallelic polymorphisms of both cytokine promoters (-308G-->A and -863C-->A at TNF promoter sequence and -1082G-->A, -819C-->A, and -592C-->T at IL-10 promoter) were typed using biotilinated specific probes in 32 celiac patients, in 34 CD-IgAD patients, and in 96 healthy controls.


RESULTS
In CD and CD-IgAD, the -308A allele was significantly more frequent than in controls, whereas no significant differences were observed for the biallelic polymorphisms at the -863 and for the three IL-10 promoter polymorphisms. The evaluation of combined TNF and IL-10 genotypes showed in CD-IgAD a significant reduction of -308G/-1082G homozygous subjects and both in CD and CD-IgAD groups an increase of 308AA/1082GG. Accordingly, CD-IgAD patients positive both for -308A TNF and -1082A IL-10 showed an increase of TNF-alpha and a reduction of IL-10 serum levels.


CONCLUSIONS
Genetically determined increased production of TNF-alpha and reduction of IL-10 may be relevant for susceptibility to CD, mainly in IgAD, as the different allele expression at TNF and IL-10 loci seems to influence cytokine production profile.
Clinica Pediatrica R, Sezione di Patologia Generale, University of Palermo, Palermo, Italy.
F
F
Cataldo
D
D
Lio
V
V
Marino
L
L
Scola
A
A
Crivello
A M
AM
Mulè
G R
GR
Corazza
D000328:Adult; D002446:Celiac Disease / Q000097:blood / Q000150:complications / Q000235:genetics*; D002648:Child; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000235:genetics*; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006801:Humans; D017098:IgA Deficiency / Q000097:blood / Q000150:complications / Q000235:genetics*; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D017421:Sequence Analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000235:genetics*
D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10