Inhibitors of complement-mediated cytotoxicity in normal and secondary aborter sera

Area of Science:

• Immunology
• Reproductive Medicine
• Maternal-Fetal Medicine

Background:

• Secondary spontaneous abortions are associated with complement-dependent cytotoxic (CDC) antibodies targeting paternal lymphocytes.
• These antibodies are not anti-HLA but are specific for trophoblast-lymphocyte cross-reactive (TLX) antigens and are predominantly IgG.

Purpose of the Study:

• To characterize the nature of lymphocytotoxic antibodies found in patients with secondary spontaneous abortions.
• To investigate the role and characteristics of a complement inhibitor present in these sera.

Main Methods:

• Lymphocytotoxicity assays using HLA-selected cell panels.
• Absorption studies with HLA-negative trophoblast membranes.
• Chromatography (G-200 Sephadex) and ion-exchange chromatography (diethylaminoethyl cellulose) for inhibitor isolation.
• Heat and heparin absorption to characterize inhibitor properties.

Main Results:

• Trophoblast-lymphocyte cross-reactive (TLX) antibodies, predominantly IgG, were identified in sera of patients with secondary spontaneous abortions.
• A complement-dependent cytotoxic (CDC) inhibitor, distinct from the antibodies, was found in normal and aborter sera.
• The inhibitor has a high molecular weight (>250,000), is species-specific, and its activity is enhanced by heating and heparin absorption.

Conclusions:

• The findings suggest an imbalanced immune regulatory mechanism involving TLX antibodies and a specific inhibitor in secondary spontaneous abortions.
• This imbalance may involve a regulator molecule controlling the inhibitor, contributing to recurrent pregnancy loss.