Prepared by: Daniela Cihakova MD, PhD|
Definition: Autoimmune oophoritis is an autoimmune inflammation of ovaries resulting in their destruction, atrophy, and fibrosis with a loss of fertility and ovary hormonal production.
Description: Autoimmune oophoritis is a cause of premature ovarian failure (POF) in 10 percent of cases. Women with POF have premature menopause before 40 years of age (secondary amenorrhea). They stop menstruating, are infertile, and have deficient estrogen and progesterone. In some cases, usually in girls with autoimmune polyglandular syndrome type 1, ovaries are destroyed before the first menstruation (primary amenorrhea). There is no treatment for this condition. In girls with the polyglandular syndrome, autoantibodies can be used as a good prediction marker for future gonadal failure (more details below).
- Primary amenorrhea (menstruation has never occurred),
- secondary amenorrhea (menstruation appeared at puberty but subsequently stopped),
- infertility, and
- sex hormone deficiency
Diagnosis: StCA autoantibodies or antibodies directly against P450c17 are good predictive markers for future gonadal failure. In studies, ovarian laparoscopy biopsy is provided, but it is not routine since no treatment is available.
Treatment: No immunosuppressive has been proven safe and effective by prospective randomized placebo-controlled study. There are few reports on a successful ovulation-inducing treatment with high dosages of corticosteroids. However because of risks, long term prednisone treatment is not routinely used. Hormone replacement therapy is used, but it can not return fertility.
Pathogenesis: Oophoritis is an autoimmune disease. Autoimmune oophoritis is characterized by lymphocytic infiltration. It was found that patients with autoimmune polyglandular syndrome type 1 can have autoantibodies (StCA), which react both against steroid-producing cells in adrenal glands and gonad as well. Based on positivity to StCA antibodies in women with PAS I, it is possible to predict the development of hypogonadotropic hypogonadism. Main antigens for StCA are P450scc and P450c17. P450c17 is present both in gonads and adrenal glands.
- HLA class II association. – DR3.
- Association with other autoimmune diseases – oophoritis is very common as part of autoimmune polyglandular syndromes.
- Infiltration of theca interna of the growing follicles with monocytes and lymphocytes.
- Autoantibodies StCa or against P450c17 are present in serum.
Two mice models of autoimmune ovarian disease (AOD) are currently available:
- Autoimmune oophoritis can be induced by immunization with testis and ovarian antigen murine human zona pellucida 3 peptide (pZP3) in adjuvant. Mice develop autoimmune oophoritis and have reduced fertility. T cells specific against pZP3 transferred to normal mice caused a development of granulomatous oophoritis, but the follicular development remained normal. It is worth to notice that a large body of literature describes current research towards developing contraceptive vaccines based on zona pellucida (ZP) antigens.
- Spontaneous orchitis and oophoritis is developed by certain mice strain after thymectomy 3 days after birth (d3tx). They develop ovarian inflammation and atrophy with loss of oocytes D3tx mice have a deficiency of T cells bearing interleukin-2 receptors (IL-2R) or CD25 antigens in the unstimulated state. Diseases can be prevented by transfer of such a cell population from normal mice. An important role of central T cell tolerance was recently shown in PAS I as well, where oophoritis is very common.
Recently, a primate AOD model was described. Macaques were immunized with pZP3 in adjuvant and developed T cells infiltration in ovarian intersticium. T cells were co-localized with MHC II positive macrophages. Granulomatosis infiltration is rarer in monkey model then in murine model.