Autoantibodies against complement C1q correlate with the thyroid function in patients with autoimmune thyroid disease

Abstract

SummaryAutoantibodies against complement C1q (anti-C1q) have been well described in patients with systemic lupus erythematosus, where they correlate with the occurrence of severe lupus nephritis. However, data on anti-C1q in organspecific autoimmune diseases are scarce. In order to determine the prevalence of anti-C1q in patients with autoimmune thyroid disorders (AITD) and a possible association with thyroid function, we measured prospectively antiC1q in 23 patients with Graves' disease (GD) and 52 patients with Hashimoto's thyroiditis (HT). Anti-C1q levels were correlated with parameters of thyroid function and autoantibodies against thyroperoxidase, thyroglobulin and thyroid stimulating hormone (TSH) receptor. Twenty-one patients with multi-nodular goitre and 72 normal blood donors served as controls. We found elevated concentrations of anti-C1q more frequently in patients with AITD than in controls: seven of 23 (30%) patients with GD and 11 of 52 (21%) patients with HT, compared with one of 21 (5%) patients with multinodular goitre and six of 72 (8%) normal controls. Anti-C1q levels did not correlate with thyroid autoantibodies. However, in GD absolute levels of antiC1q correlated negatively with TSH and positively with free thyroxine (FT4) and triiodothyronine (FT3). In contrast, in HT, anti-C1q correlated positively with TSH levels. No correlation between TSH and thyroid autoantibodies was found. In conclusion, we found an increased prevalence of anti-C1q in patients with AITD and their levels correlated with the thyroid function in both GD and HT. This correlation seems to be independent of thyroid autoantibodies. Therefore, anti-C1q might point to a pathogenic mechanism involved in the development of AITD that is independent of classical thyroid autoantibodies.

C1q, antibodies and anti-C1q autoantibodies

“…The anti-C1q autoantibodies were initially detected in SLE sera but by now the presence of anti-C1q autoantibodies has been studied in several autoimmune (Coremans et al, 1995a;Siegert et al, 1990Siegert et al, , 1992 and renal conditions (Coremans et al, 1992;Siegert et al, 1992) as well as in infectious diseases (Trendelenburg, 2005). In the healthy population anti-C1q autoantibodies can be detected in 2-8% of the individuals (Horvath et al, 2001;Potlukova et al, 2008;Siegert et al, 1992;Trendelenburg et al, 1999b;Wener et al, 1989) which increases with age (Siegert et al, 1993). Conditions characterized by high anti-C1q antibody prevalence are: Hypocomplementaemic Urticarial Vasculitis Syndrome (HUVS) 100% (Wisnieski and Jones, 1992), mixed connective tissue disease (94%), Felty's syndrome (76%) and SLE (30-60%) (Potlukova et al, 2008;Siegert et al, 1992;Sinico et al, 2009;Trendelenburg, 2005).…”

“…In the healthy population anti-C1q autoantibodies can be detected in 2-8% of the individuals (Horvath et al, 2001;Potlukova et al, 2008;Siegert et al, 1992;Trendelenburg et al, 1999b;Wener et al, 1989) which increases with age (Siegert et al, 1993). Conditions characterized by high anti-C1q antibody prevalence are: Hypocomplementaemic Urticarial Vasculitis Syndrome (HUVS) 100% (Wisnieski and Jones, 1992), mixed connective tissue disease (94%), Felty's syndrome (76%) and SLE (30-60%) (Potlukova et al, 2008;Siegert et al, 1992;Sinico et al, 2009;Trendelenburg, 2005). Anti-C1q autoantibodies have also been described to occur at increased frequencies in infectious diseases such as HIV (Prohaszka et al, 1999) and hepatitis C (Saadoun et al, 2006).…”

Anti-C1q Autoantibodies, Novel Tests, and Clinical Consequences

“…In the healthy population the prevalence of anti-C1q autoantibodies ranges between 2 and 8% (Wener et al, 1989; Siegert et al, 1992a; Trendelenburg et al, 1999; Horvath et al, 2001a; Potlukova et al, 2008) and increases with age (Siegert et al, 1993). Hypocomplementemic Urticarial Vasculitis Syndrome (HUVS) represents the clinical condition with the highest percentage of anti-C1q positivity; 100% (Wisnieski and Jones, 1992).…”

“…Hypocomplementemic Urticarial Vasculitis Syndrome (HUVS) represents the clinical condition with the highest percentage of anti-C1q positivity; 100% (Wisnieski and Jones, 1992). Other conditions characterized by high anti-C1q antibody prevalence are, mixed connective tissue disease (94%), Felty’s syndrome (76%), and SLE (30–60%) (Siegert et al, 1992a; Trendelenburg, 2005; Potlukova et al, 2008; Sinico et al, 2009). The occurrence of anti-C1q autoantibodies was shown to have familial clustering, indicating that there is a genetic risk factor that together with environmental cues may precipitate the production of these antibodies (Hunnangkul et al, 2008).…”

“…One possible scenario could be that the natural mechanisms that would limit excessive complement activation on dying cells would be overruled (Trouw et al, 2007, 2008) resulting in lysis of the cells and exposure of autoantigenic components to the immune system. The observation that anti-C1q autoantibodies are also observed in autoimmune thyroid diseases and that their levels correlate with thyroid function (Potlukova et al, 2008) may suggest that the effect of anti-C1q antibodies amplifying immune-complex mediated damage only in the kidney is incomplete and that the presence of anti-C1q antibodies may enhance tissue damage in several other, unexpected clinical conditions.…”