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Role of Anti-C1q Autoantibodies in Pregnancy

Role of Anti-C1q Autoantibodies in Pregnancy

Recruiting
18 years and older
Female
Phase N/A

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Overview

Preeclampsia (PE) is a very frequent obstetric complication. C1q, the first recognition molecule of the classical pathway of complement system (C), represents a double-edged molecule in determining pregnancy outcomes. In animal models, C1q deficiency caused the development of a dysfunctional placenta and PE-like symptoms. Conversely, lower levels of C components were detected in the sera of patients with PE due to C consumption and increased deposition of activated C components in the placenta, as well as to the binding to placental apoptotic bodies, syncytiotrophoblast microvesicles (STBM) and debris which are increased in the circulation of patients with PE.

C1q is a hexameric glycoprotein of 460kDa composed by six copies of three polypeptide chains A, B and C, each made by a C-terminal globular head (gC1q) and a N-terminal collagen-like region (CLR). This molecule can be the target of an antibody response. Autoantibodies targeting C1q were first recognized in the serum of Systemic Lupus Erythematosus (SLE) patients. The presence of anti-C1q autoantibodies was also detected in patient affected by autoimmune disease (ie, kidney disorders, vasculitis, thyroiditis). Almost all of these autoimmune disorders are associated with an increased risk of developing PE during pregnancy.

Anti-C1q detection mainly concerns the prediction of the onset of lupus nephritis (LN) in SLE patients. Although anti-C1q autoantibodies do not deplete circulating C1q, their presence in maternal circulation and in placenta may trigger improper C activation and impair C1q activity. In pregnancies complicated by autoimmune affection such as SLE, autoimmune thyroid disorders and Antiphospholipid syndrome (APS) the prevalence of anti-C1q appeared to be higher than in control pregnancies and associated with miscarriage. High levels of anti-C1q have been found in a group of Japanese patients suffering recurrent pregnancy loss (RPL). In a group of anti-C1q positive healthy pregnancies and LN patients was assessed whether C1q autoantigenic behaviour could vary among individuals with or without correlated manifestation. Sera from healthy pregnancies and LN patients were screened for the presence of autoantibodies against the CLR fragment and/or the gC1q: antibodies against gC1q were found in both groups, whereas anti-CLR were only detected in the LN one, suggesting that only the latter may have a pathogenic role. Despite this, the biological functions of anti-C1q remain far from clear

Eligibility

Inclusion Criteria Group 1. Women occurring physiological pregnancies that sign the consent to participate in the study and agree to spontaneously return to the maternal hospital 40 days after delivery.

Group 2. Patients diagnosed for PE (hypertension arisen suddenly after the 20th week of pregnancy with associated proteinuria, greater than or equal to 300 mg/24 hours often corresponding to 30 mg/dL (1+) on a single sample).

Group 3. Women affected by SLE, APS, or autoimmune thyroiditis attending the medically assisted procreation department or the Department of Rheumatology, Division of Internal Medicine, University Medical Centre Ljubljana, Ljubljana, Slovenia

Exclusion criteria

  1. Women aged under 18 years
  2. Viral or bacterial blood transmitted infections.
  3. Patients whose informed consent cannot be obtained.

Study details
    Pre-Eclampsia

NCT06317467

IRCCS Burlo Garofolo

4 September 2025

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