Anti-nuclear antibody,anti-DNA,and aCL in Graves’ disease patients treated with propyluracil or methimazole

Abstract

One hundred and forty patients with Graves’disease [32 new patients, 54 treated with propylthiouracil (PTU) for a mean of 27.2 months and 54 treated with methimazole (MMI) for a mean of 48.6 months] were tested for anti-thyroid microsomal antibody (AMA), anti-thyroglobulin antibody (ATA), thyroid binding inhibitory immunoglobulin (TBII), and the non organ specific autoantibodies [i.e., anti-nuclear antibody (ANA), anti-double stranded DNA antibody (anti-dsDNA Ab), anti-cardiolipin antibody (aCL Ab) and anti-β₂-glycoprotein I antibody (IgG β₂ GPI)]. Treatment with MMI or PTU produced a significant difference in IgG aCL Ab production but not in ANA, dsDNA Ab, IgM aCL or IgG β₂ GPI. For those treated with MMI but not those treated with PTU, ANA and anti-dsDNA Ab were positively correlated. IgG and IgM aCL Ab were positively correlated overall and for those on MMI but not PTU treatment. No significant difference was found for any of the four non organ specific antibodies in AMA positive or negative patients but there was a significant difference in IgG aCL positivity rates for ATA positive and negative patients. On the other hand, ANA negative patients were significantly more likely to have higher TBII values. These results suggest that the appearance of the non organ specific autoantibodies is probably largely a coincidental effect of polyclonal activation - except, perhaps, for IgG aCL, which may be related to treatment.

Keywords

autoantibodies Graves’ disease methimazole propylthiouracil

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References

Davies TF. The pathogenesis of Graves’ disease. In Braverman LE , Utiger R eds. The thyroid: a fundamental and clinical text, eighth edition Philadelphia: Lippincott Williams & Wilkins , 2000: 518-531.

Saravanan P , Dayan CM. Thyroid autoantibodies . Endocrin Metab Clin North Am 2001; 30: 315-337 .

Inamo Y , Harada K. Antinuclear antibody positivity in pediatric patients with autoimmune thyroid disease . J Rheumatol 1997; 24: 576-578 .

Baethge BA , Levine SN , Wolf RE. Antibodies to nuclear antigens in Graves’ disease . J Clin Endocrinol Metab 1988; 66: 485-488 .

Hofbauer LC , Spitzweg C , Heufelder AE. Graves’ disease associated with the primary antiphospholipid syndrome . J Rheumatol 1996; 23: 1435-1437 .

Kiljanski JI , Peele K , Stachura I et al. Antibodies against striated muscle, connective tissue and nuclear antigens in patients with thyroid-associated ophthalmopathy: should Graves’ disease be considered a collagen disorder ? J Endocrinol Invest 1997; 20: 585-591 .

Wartofsky L , Glinoer D , Solomon B et al. Differences and similarities in the diagnosis and treatment of Graves’ disease in Europe, Japan, and the United States . Thyroid 1991; 1: 129-135 .

Feldt-Rasmussen U , Glinoer D , Orgiazzi J. Reassessment of antithyroid drug therapy of Graves’ disease . Annu Rev Med 1993; 44: 323-334 .

Volpe R. The immunomodulatory effects of anti-thyroid drugs are mediated via actions on thyroid cells, affecting thyrocyte-immunocyte signaling: a review . Curr Pharm Des 2001; 7: 451-460 .

10.

Lavard L , Perrild H , Jacobsen BB , Hoier-Madsen M , Bendinelli G , Vitti P. Prevalence of thyroid peroxidase, thyroglobulin and thyrotropin receptor antibodies in a long-term follow-up of juvenile Graves disease . Autoimmunity 2000; 32: 167-172 .

11.

Loviselli A , Velluzzi F , Pala R et al. Circulating antibodies to DNA-related antigens in patients with autoimmune thyroid disorders . Autoimmunity 1992; 14: 33-36 .

12.

Petri M , Karlson EW , Cooper DS , Ladenson PW. Autoantibody tests in autoimmune thyroid disease: a case-control study . J Rheumatol 1991; 18: 1529-1531 .

13.

Tachi J , Amino N , Iwatani Y et al. Increase in antideoxyribonucleic acid antibody titer in postpartum aggravation of autoimmune thyroid disease . J Clin Endocrinol Metab 1988; 67: 1049-1053 .

14.

Katakura M , Yamada T , Aizawa T et al. Presence of antideoxyribo-nucleic acid antibody in patients with hyperthyroidism of Graves’ disease . J Clin Endocrinol Metab 1987; 64: 405-408 .

15.

Morita S , Arima T , Matsuda M. Prevalence of nonthyroid specific autoantibodies in autoimmune thyroid diseases . J Clin Endocrinol Metab 1995; 80: 1203-1206 .

16.

Veitch J , Wilson R , Jenkins C , Thomson JA. Failure to detect anti-deoxyribonucleic acid antibody in Graves’ disease in Caucasians . Autoimmunity 1989; 2: 191-194 .

17.

Konstadoulakis MM , Kroubouzos G , Tosca A et al. Thyroid auto-antibodies in the subsets of lupus erythematosus: correlation with other autoantibodies and thyroid function . Thyroidology 1993; 5: 1-7 .

18.

Baker JR Jr , Miller FW , Steinberg AD , Burman KD. Thyroid stimulating and thyrotrophin binding-inhibitory immunoglobulin activity in patients with systemic lupus erythematosus having thyroid function abnormalities . Thyroid 1991; 1: 229-234 .

19.

Scofield RH. Autoimmune thyroid disease in systemic lupus erythematosus and Sjogren’s syndrome . Clin Exp Rheumatol 1996; 14: 321-330 .

20.

Boey ML , Fong PH , Lee JS , Ng WY , Thai AC. Autoimmune thyroid disorders in SLE in Singapore . Lupus 1993; 2: 51-54 .

21.

Searles RP , Plymate SR , Troup GM. Familial thionamide-induced lupus syndrome in thyrotoxicosis . J Rheumatol 1981; 8: 498-500 .

22.

Takuwa N , Kojima I , Ogata E. Lupus-like syndrome - a rare complication in thionamide treatment for Graves’ disease . Endocrinol Jpn 1981; 28: 663-667 .

23.

Berkman EM , Orlin JB , Wolfsdorf J. An antineutrophil antibody associated with a propylthiouracil induced lupus-like syndrome . Transfusion 1983; 23: 135-138 .

24.

Sato-Matsumura K , Koizumi H , Matsumura T , Takahashi T , Adachi K , Ohkawara A. Lupus erythematosus-like syndrome induced by thiamazole and propylthiouracil . J Dermatol 1994; 21: 501-507 .

25.

Kawachi Y , Nukaga H , Hoshino M , Iwata M , Otsuka F. ANCA-associated vasculitis and lupus-like syndrome caused by methimazole . Clin Exp Dermatol 1995; 20: 345-347 .

26.

Yamada A , Sato K , Hara M et al. Propylthiouracil-induced lupus-like syndrome developing in a Graves’ patient with a sibling with systemic lupus erythematosus . Int Medicine 2002; 41: 1204-1208 .

27.

Takahashi A , Tamura A , Ishikawa O. Antiphospholipid antibody syndrome complicated by Grave’s disease . J Dermatol 2002; 29: 776-780 .

28.

Diez JJ , Doforno RA , Iglesias P , Sastre J , Gomez-Pan A , Borbujo J. Anticardiolipin antibodies in autoimmune thyroid disease . J Clin Lab Immunol 1993; 40: 125-134 .

29.

Paggi A , Caccavo D , Ferri GM et al. Anti-cardiolipin antibodies in auto-immune thyroid diseases . Clin Endocrinol (Oxf) 1994; 40: 329-333 .

30.

Cabiedes J , Cabral AL , Alarcon-Segovia D. Clinical manifestation of the antiphospholipid syndrome in patients with systemic lupus erythematosus associate more strongly with anti-β2 glycoprotein I than with antiphospholipid antibodies . J Rheumatol 1995; 22: 1899-1906 .

31.

El-Kadi HS , Keil LB , DeBari VA. Analytical and clinical relationships between human IgG autoantibodies to beta 2 glycoprotein I and anticardiolipin antibodies . J Rheumatol 1995; 22: 2233-2237 .

32.

Sanmarco M , Soler C , Christides C et al. Prevalence and clinical significance of IgG isotype anti-beta 2-glycoprotein I antibodies in antiphospholipid syndrome: a comparative study with anticardiolipin antibodies . J Lab Clin Med 1997; 129: 499-506 .