Role of Anti-C1q Autoantibodies in Pregnancy

NCT06317467 | Recruiting

• 1 other identifier: RC 01/2023
• Study Type: observational
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Pre-Eclampsia

Keywords

Anti-C1q autoantibodies; Intra Uterine Growth Restriction (IUGR); Pre-eclampsia

Outcome Measures

Primary Outcomes (8)

• Between groups difference in percentage of anti-gC1q compared to the total anti-C1q autoantibodies

  8-12 weeks of gestation

• Between groups difference in percentage of anti-cC1q compared to the total anti-C1q autoantibodies

  8-12 weeks of gestation

• Between groups difference in percentage of anti-gC1q compared to the total anti-C1q autoantibodies

  20-24 weeks of gestation.

• Between groups difference in percentage of anti-cC1q compared to the total anti-C1q autoantibodies

  20-24 weeks of gestation.

• Between groups difference in percentage of anti-gC1q compared to the total anti-C1q autoantibodies

  34-38 weeks of gestation.

• Between groups difference in percentage of anti-cC1q compared to the total anti-C1q autoantibodies

  34-38 weeks of gestation.

• Between groups difference in percentage of anti-gC1q compared to the total anti-C1q autoantibodies

  40-50 days after delivery.

• Between groups difference in percentage of anti-cC1q compared to the total anti-C1q autoantibodies

  40-50 days after delivery.

Study Arms (3)

Women with physiological pregnancies

Control group

Other: Blood sampling

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

Other: Blood sampling

Women affected by SLE, APS, or autoimmune thyroiditis

Patients attending the medically assisted procreation department or the Department of Rheumatology, Division of Internal Medicine, University Medical Centre Ljubljana, Ljubljana, Slovenia

Other: Blood sampling

Interventions

Blood sampling OTHER

Four blood samples will be collected, in conjunction with the collection of samples already programmed for assistance during pregnancy: blood sampling for the B-test (within the 13th week of gestation), at the blood test centre of the Institute for Maternal and Child Health, IRCCS Burlo Garofolo; blood sampling for toxoplasmosis or blood sugar level, upon execution of the morphological ultrasound scanning (around the 20th and 34th weeks of gestation), at the blood test centre of the Institute for Maternal and Child Health, IRCCS Burlo Garofolo, as well. Finally, 40 days after delivery, during routine gynaecological control after the puerperium.

Patients diagnosed for PE; Women affected by SLE, APS, or autoimmune thyroiditis; Women with physiological pregnancies

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Pregnant women, women attending the medically assisted procreation

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• IRCCS Burlo Garofolo: lead

Study Sites (1)

Institute for Maternal and Child Health - IRCCS "Burlo Garofolo"

Trieste, 34137, Italy

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples

MeSH Terms

Conditions

Pre-Eclampsia

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Hypertension, Pregnancy-Induced; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Central Study Contacts

Chiara Agostinis, BSc

CONTACT

+39.040.5588652; chiara.agostinis@burlo.trieste.it

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2024
• First Posted: March 19, 2024
• Study Start: September 13, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 19, 2024

Record last verified: 2024-03

Locations

IT (1)