Anti-C1q antibodies (anti-C1q) have been implicated in the pathogenesis of autoimmune diseases, including autoimmune thyroid disorders (AITD). The aim of this study was to evaluate the association between anti-C1q and thyroid function in pregnancy-associated AITD. In 96 pregnant women screened positive for AITD (thyroid dysfunction and/or antibodies against thyroperoxidase - TPOAb), anti-C1q were measured during the 9-11th gestational week and after delivery (median 16 months after delivery), and compared to the corresponding serum levels of thyroid hormones. As controls, 80 healthy pregnant women, 72 non-pregnant AITD patients and 72 blood donors were included. In the non-pregnant AITD group, two serum samples ≥ 6 months apart were analysed. Compared to blood donors, anti-C1q levels were substantially higher in all pregnant women analysed. In pregnancy, anti-C1q levels were higher in the TPOAb-positive women than in controls (37 versus 17·5%, P < 0·0001). Anti-C1q-positive pregnant women screened positive for AITD had higher thyroid-stimulating hormone (TSH) levels than anti-C1q-negative women (2·41 versus 1·94 mU/l, P = 0·01), and TSH correlated positively with anti-C1q (r = 0·226, P = 0·045) in the TPOAb-positive women. After delivery, serum levels of anti-C1q decreased in the positively screened TPOAb-negative women (8·8 versus 5·9 U/l, P = 0·002), but not in the TPOAb-positive ones, and they no longer correlated with TSH. Anti-C1q antibody levels increase during pregnancy in general and even more in the context of AITD, where they correlate with thyroid stimulating hormone levels.

3rd Department of Medicine General University Hospital and 1st Faculty of Medicine Charles University Prague Czech Republic

Division of Internal Medicine and Laboratory of Clinical Immunology University Hospital Basel

Division of Internal Medicine University Hospital Basel

Institute of Biophysics and Informatics 1st Faculty of Medicine Charles University Prague Prague Czech Republic

Institute of Clinical Biochemistry and Laboratory Medicine General University Hospital Prague Czech Republic

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Guleria I, Sayegh MH. Maternal acceptance of the fetus: true human tolerance. J Immunol 2007; 178:3345–51. PubMed

Borchers AT, Naguwa SM, Keen CL, Gershwin ME. The implications of autoimmunity and pregnancy. J Autoimmun 2010; 34:J287–99. PubMed

Perricone C, de Carolis C, Perricone R. Pregnancy and autoimmunity: a common problem. Best Pract Res Clin Rheumatol 2012; 26:47–60. PubMed

Potlukova E, Potluka O, Jiskra J et al Is age a risk factor for hypothyroidism in pregnancy? An analysis of 5223 pregnant women. J Clin Endocrinol Metab 2012; 97:1945–52. PubMed

Limanova Z, Springer D. Thyreopathy examination during pregnancy – results of pilot project. Cas Lek Cesk 2011; 150:389–93. PubMed

Stagnaro‐Green A, Abalovich M, Alexander E et al Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid 2011; 21:1081–125. PubMed PMC

Stagnaro‐Green A, Schwartz A, Gismondi R, Tinelli A, Mangieri T, Negro R. High rate of persistent hypothyroidism in a large‐scale prospective study of postpartum thyroiditis in southern Italy. J Clin Endocrinol Metab 2011; 96:652–7. PubMed

Klecha AJ, Barreiro Arcos ML, Frick L, Genaro AM, Cremaschi G. Immune–endocrine interactions in autoimmune thyroid diseases. Neuroimmunomodulation 2008; 15:68–75. PubMed

Kawashima A, Tanigawa K, Akama T, Yoshihara A, Ishii N, Suzuki K. Innate immune activation and thyroid autoimmunity. J Clin Endocrinol Metab 2011; 96:3661–71. PubMed

Weetman A, Cohen SB, Oleesky DA, Morgan BP. Terminal complement complexes and C1/C1 inhibitor complexes in autoimmune thyroid disease. Clin Exp Immunol 1989; 77:25–30. PubMed PMC

Weetman A, Tandon N, Morgan BP. Antithyroid drugs and release of inflammatory mediators by complement‐attacked thyroid cells. Lancet 1992; 340:633–6. PubMed

Nauta AJ, Castellano G, Xu W et al Opsonization with C1q and mannose‐binding lectin targets apoptotic cells to dendritic cells. J Immunol 2004; 173:3044–50. PubMed

Ogden CA, deCathelineau A, Hoffmann PR et al C1q and mannose binding lectin engagement of cell surface calcireticulin and CD91 initiates macropinocytosis and uptake of apoptotic bodies. J Exp Med 2001; 194:781–96. PubMed PMC

Carroll M. Innate immunity in the etiopathology of autoimmunity. Nat Immunol 2001; 2:1089–90. PubMed

Beurskens FJ, van Schaarenburg RA, Trouw LA. C1q, antibodies and anti‐C1q autoantibodies. Mol Immunol 2015; 68:6–13. PubMed

Lu J, Teh BK, Wang L et al The classical and regulatory functions of C1q in immunity and autoimmunity. Cell Mol Immunol 2008; 5:9–21. PubMed PMC

Singh J, Ahmed A, Girardi G. Role of complement component C1q in the onset of preeclampsia in mice. Hypertension 2011; 58:716–24. PubMed

Mahler M, van Schaarenburg RA, Trouw LA. Anti‐C1q autoantibodies, novel tests, and clinical consequences. Front Immunol 2013; 4:117. PubMed PMC

Potlukova E, Kralikova P. Complement component c1q and anti‐c1q antibodies in theory and in clinical practice. Scand J Immunol 2008; 67:423–30. PubMed

Trendelenburg M, Lopez‐Trascasa M, Potlukova E et al High prevalence of anti‐C1q antibodies in biopsy‐proven active lupus nephritis. Nephrol Dial Transplant 2006; 21:3115–21. PubMed

Potlukova E, Jiskra J, Limanova Z et al Autoantibodies against complement C1q correlate with the thyroid function in patients with autoimmune thyroid disease. ClinExp Immunol 2008; 153:96–101. PubMed PMC

Daponte A, Deligeoroglou E, Pournaras S et al Interleukin‐15 (IL‐15) and anti‐C1q antibodies as serum biomarkers for ectopic pregnancy and missed abortion. Clin Dev Immunol 2013; 2013:637513. PubMed PMC

Springer D, Zima T, Limanova Z. Reference intervals in evaluation of maternal thyroid function during the first trimester of pregnancy. Eur J Endocrinol 2009; 160:791–7. PubMed

Springer D, Bartos V, Zima T. Reference intervals for thyroid markers in early pregnancy determined by 7 different analytical systems. Scand J Clin Lab Invest 2014; 74:95–101. PubMed

Trendelenburg M, Marfurt J, Gerber I, Tyndall A, Schifferli JA. Lack of occurrence of severe lupus nephritis among anti‐C1q autoantibody‐negative patients. Arthritis Rheum 1999; 42:187–8. PubMed

Stoyanova V, Petrova S, Tchorbadjieva M, Deliyska B, Vasilev V, Tsacheva I. New insight into the autoimmunogenicity of the complement protein C1q. Mol Immunol 2011; 48:678–82. PubMed

Mosca M, Strigini F, Doria A et al Anti‐C1q antibodies in pregnant patients with systemic lupus erythematosus. Clin Exp Rheumatol 2007; 25:449–52. PubMed

Weetman AP. Immunity, thyroid function and pregnancy: molecular mechanisms. Nat Rev Endocrinol 2010; 6:311–8. PubMed

Wisnieski JJ, Jones SM. Comparison of autoantibodies to the collagen‐like region of C1q in hypocomplementemic urticarial vasculitis syndrome and systemic lupus erythematosus. J Immunol 1992; 148:1396–403. PubMed

Kravitz MS, Shoenfeld Y. Autoimmunity to protective molecules: is it the perpetuum mobile (vicious cycle) of autoimmune rheumatic disease? Nat Clin Pract Rheumatol 2006; 2:481–90. PubMed

Parkes AB, Adams H, Othman S, Hall R, John R, Lazarus JH. The role of complement in the pathogenesis of postpartum thyroiditis: ultrasound echogenicity and the degree of complement‐induced thyroid damage. Thyroid 1996; 6:177–82. PubMed

Okosieme OE, Parkes AB, McCullough B et al Complement activation in postpartum thyroiditis. Q J Med 2002; 95:173–9. PubMed