Impaired Human Ovarian Follicular Fluid Complement Function in Hereditary Angioedema

Abstract

We sought and detected functionally active complement in human ovarian follicular fluid obtained during the peri-ovulatory period. All the functional complement activities tested, including total haemolytic complement, classical pathway activity, alternative pathway activity and C1 inhibitor function were present with values within the normal serum range. Active complement in follicular fluid is relevant for the function of the enzymatic multifactorial mechanism of ovulation. The presence in hereditary angioedema patients of both complement (C1 inhibitor deficiency and chronically consumed complement) and ovarian abnormalities (cystic ovaries), led us to study complement function in the follicular fluid of women of reproductive age affected with hereditary angioedema. In contrast to healthy women, hereditary angioedema patients showed dramatically reduced classical pathway activity and undetectable functional and antigenic C1 inhibitor. C4 was very low, while C3 and B were slightly reduced or within the normal serum range. This complement profile was also detected in patients' sera. Since hereditary angioedema patients often show cystic ovaries (polycystic or multifollicular), the presence of multifollicular ovaries in the two patients studied, along with complement dysfunction, may be relevant. These findings, as well as the normalisation of the ovaries found by us in hereditary angioedema patients and in the patients reported here who were undergoing danazol treatment, and the increase in C1 inhibitor and the improvement of clinical symptoms, suggest a further link between complement and ovarian function.

Decay-accelerating factor in the periovulatory rat ovary

“…Coupled with previous reports that complement regulators are detected in the ovary of human and other species, our findings strongly indicate that DAF may play a crucial role in preventing damage that would otherwise be induced by activation of the complement cascade, supporting the reports of a correlation between deteriorating complement function and cystic or multifollicular ovaries in women with hereditary angioedema (Perricone et al 2000). We hypothesize that a lack of functional DAF or Figure 7 mRNA expression profile of CD59 in ovary.…”

International consensus and practical guidelines on the gynecologic and obstetric management of female patients with hereditary angioedema caused by C1 inhibitor deficiency

“…171,172 However, the PREHAEAT study did not reveal a higher frequency of polycystic ovary syndrome in the HAE-C1-INH population. The rate was found to be 4.7% compared with 5% to 10% in the general population in Europe (evidence level III).…”

Complement System and Rheumatoid Arthritis: Relationships with Autoantibodies, Serological, Clinical Features, and Anti-TNF Treatment

“…In all the subjects reported herein, C4 concentrations were studied by means of radial immunodiffusion (mg/dl), and C3 by nephelometry according to standard methods (mg/dl) (11). Total hemolytic complement (THC) activity was measured by the Mayer's 50 percent hemolysis method (expressed as CH50, U/ml), as reported previously (12). Normal values were considered the mean observed in healthy subjects ±2 standard deviations (SD).…”