Allele 2 of interleukin-1 receptor antagonist gene increases the risk of thyroid peroxidase antibodies in subacute thyroiditis.
Subacute granulomatous thyroiditis (SAT) is a self-limiting systemic inflammatory disorder with possible transient expression of thyroid antibodies. Persistent hypothyroidism is uncommon. The interleukin-1 receptor antagonist IL-1ra is an inhibitor of IL-1 activity and allele 2 of the IL-1ra gene is associated with inflammatory diseases and IL-1ra production. Forty-eight subjects with SAT were investigated. Polymorphisms of IL-1ra, IL-1beta-511 and TNFalpha genes were studied with respect to thyroid peroxidase antibodies (TPOab), thyroglobulin antibodies, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Serum IL-1ra levels were measured. An increased allelic frequency (43% vs 22%, p=0.039) and carriage rate (79% vs 41%, p=0.018) for IL-1ra allele 2 were observed with expression of TPOab in 14 (29.2%) subjects compared with those with negative findings. The carriage rate for both IL-1ra allele 2 and IL-1beta-511 allele 2 was also increased with TPOab expression (71% vs 27%, p=0.004, respectively). No difference in allele frequency or carriage rate was found compared with healthy controls. Serum IL-1ra levels correlated with S-CRP (r=0.41, p=0.004) and ESR (r=0.34, p=0.016), but the association with genes or thyroid antibodies was statistically insignificant. S-CRP levels and ESR were lower and negatively correlated with expression of TPOab (r=-0.27, p=0.046 and r=-0.32, p=0.017). This study describes the multiplicity of the mechanisms responsible for the severity of the acute-phase response during the course of SAT. IL-1ra may have a significant anti-inflammatory role in SAT. Presence of IL-1ra allele 2 increases the risk of developing TPOab.
Luotola
K
K
Department of Medicine, Tampere University Hospital, Finland. kari.luotola@uta.fi
Mantula
P
P
Salmi
J
J
Haapala
A M
AM
Laippala
P
P
Hurme
M
M
D000328:Adult; D000368:Aged; D000483:Alleles; D001323:Autoantibodies / Q000097:blood; D001483:Base Sequence; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D017931:DNA Primers / Q000235:genetics; D005260:Female; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000235:genetics; D007453:Iodide Peroxidase / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012795:Sialoglycoproteins / Q000235:genetics*; D013954:Thyroglobulin / Q000276:immunology; D013968:Thyroiditis, Subacute / Q000201:enzymology / Q000209:etiology / Q000235:genetics* / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D001323:Autoantibodies; D017931:DNA Primers; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D013954:Thyroglobulin; D007453:Iodide Peroxidase