SSA autoantibodies associated with severely decreased free thyroxine levels in systemic autoimmune mixed connective tissue disease

Background: Mixed connective tissue disease (MCTD) is a systemic autoimmune disease with variable symptoms and autoantibodies. Antinuclear antibody positivity is more common in autoimmune thyroid diseases with higher levels of antibodies to thyroid peroxidase (TPO) or thyroglobulin (Tg) leading to elevated TSH levels. Intracellular SSA autoantibodies have a direct role in tissue damage with a prevalence of 33% in MCTD.

Aims: To investigate the role of SSA autoantibodies in thyroid autoimmunity in MCTD patients. The effect of SSA autoantibodies on thyroid hormone levels was investigated in the presence and absence of thyroid autoimmunity.

Methods: Thirty-three patients with MCTD [41±10 years, 32 females and 1 male] and 34 healthy controls [33±14 years, 30 females and 4 males] were studied. Thyroid hormones (TSH, FT₄ and FT₃) were measured by luminescence immunoassay. Enzyme-linked immunosorbent assay was used for the detection of anti-TPO and anti-Tg autoantibodies. Biochemical data are presented as geometric mean with 95% confidence interval except for age and  FT₃/FT₄ ratio, which are presented as mean±SD.

Results: Significant differences in age and serum FT₄ levels were observed between MCTD patients and controls (41±10 vs. 33±14 years, p<0.0089 and 8.83(3.55-22) vs. 10.82(7.33-15.96) pmol/l, p<0.0229, respectively). The difference in serum TSH and FT₄ levels was significant between SSA autoantibody positive MCTD patients and controls [2.43(0.42-13.96) vs. 1.63(0.75-3.53) mIU/ml, p<0.0405 for TSH, 6.59(2.22-19.53) vs. 10.82(7.33-15.96) pmol/l, p<0.0001 for FT₄]. The greater decrease in serum FT₄ levels could be demonstrated by the presence of SSA in combination with anti-Tg [3.74(1.37-10.18) vs. 11.05(8.57-14.24) pmol/l, p<0.001] or anti-TPO autoantibodies [4.68(1.65-13.28) vs. 11.75(6.05-22.8) pmol/l, p<0.0001] compared to those thyroid antibodies alone.

Conclusions: Our results showed that SSA autoantibodies together with anti-TPO and/or anti-Tg autoantibodies resulted in a greater decrease in serum FT₄ levels than SSA autoantibodies alone. The effect of SSA autoantibodies on FT₄ levels may be manifested in the absence of thyroid autoimmunity. These results highlight the importance of screening for thyroid hormone and autoantibody levels in MCTD patients regardless of thyroid autoimmunity.