Immunogenetic characteristics of patients with autoimmune gastritis.
OBJECTIVE
To explore whether predisposition to autoimmune gastritis (AIG) is found in human leukocyte antigen (HLA), cytokine or killer cell immunoglobulin-like receptor (KIR) gene variations.


METHODS
Twelve Finnish patients with autoimmune-type severe atrophy of the gastric corpus were included. The patients' serum was analyzed for pepsinogen I and Helicobacter pylori (H. pylori) antibodies. DNA was separated and the patients were genotyped for HLA-A, B, Cw, DRB1 and DQB1 antigens, and studied for single nucleotide polymorphisms for the following cytokines: interleukin (IL)-1 gene cluster, IL-2, IL-4, IL-6, IL-10, IL-12, interferon gamma, transforming growth factor beta, and tumor necrosis factor alpha. Variation in KIR genes was also explored. The results were compared with prevalence of the polymorphisms in Finnish or European populations.


RESULTS
All patients had pepsinogen I levels below normal (mean: 11 microg/L, range: < 5 to 25 microg/L). Three patients had elevated H. pylori IgG antibodies, while H. pylori serology was negative in the rest of the patients. AIG patients carried significantly more often HLA-DRB1*04 (58%) and DQB1*03 (83%) than the general Finnish population did (28% and 51%, respectively; P = 0.045 and 0.034 by the Fisher's exact test). No patient was positive for HLA-B8-DRB1*03, a well-established autoimmune marker. Neither cytokine polymorphisms nor KIR gene variation showed association with AIG.


CONCLUSIONS
As explored with modern DNA-based methods, HLA-DRB1*04 and DQB1*03 alleles, but not HLA-B8-DRB1*03, may predispose to AIG.
Oksanen
Aino Mirjam
AM
Herttoniemi Hospital, Health Centre, City of Helsinki, PO Box 6300, 00099 Helsinki, Finland. aino.oksanen@hel.fi
Haimila
Katri Eerika
KE
Rautelin
Hilpi Iris Kaarina
HI
Partanen
Jukka Antero
JA
D000328:Adult; D001327:Autoimmune Diseases / Q000208:ethnology / Q000235:genetics*; D016022:Case-Control Studies; D016207:Cytokines / Q000235:genetics; D018153:Czech Republic; D005260:Female; D005387:Finland; D005756:Gastritis / Q000208:ethnology / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D007558:Italy; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics
D016207:Cytokines; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C527195:HLA-DRB1*04 antigen; D008562:Membrane Glycoproteins; D024661:Potassium Channels, Inwardly Rectifying