**2.3.2 Autoantibodies**

424 Endometriosis - Basic Concepts and Current Research Trends

The role of cytokines and growth factors in the pathophysiology of endometriosis is evident. They are probably responsible for the proliferation of endometrial cells and implantation of endometrial cells or tissue. In addition, cytokines increase the tissue remodelling through their influence on matrix metalloproteinases. Probably the most important effect of cytokines on ectopic endometrial tissue is an increase in angiogenesis of ectopic endometrial tissue and neovascularisation of the affected region. Therefore, cytokines play an important role in the initiation, propagation and regulation of immune and inflammation responses. The activation of immune cells results in a burst and cascade of inflammatory cytokines.

ELISA kits are available to assess the cytokines in the serum and peritoneal fluid (PF) of endometriosis patients. PF is rich with variable cellular components including macrophages, mesothelial cells, lymphocytes, eosinophils and mastcells. Approximately 85% of PF leukocytes are macrophages. It has been hypothesized that peritoneal macrophage activation is a key step in disease initiation and progression. Activated macrophages in the peritoneal cavity of women with endometriosis are potent producers of cytokines (Bedaiwy et al., 2002). Thus, PF contains a rich mixture of cytokines. Cytokines, such as TNF-α, IL-1, IL-6, IL-8, monocyte chemoattractant protein (MCP)-1 and IFN-γ, are elevated in the PF of women with endometriosis, suggesting that they are involved in the progression of the disease. The level of IL-1 in PF is positively correlated with the progression of endometriosis, but the serum level of IL-1 seems to have no correlation with endometriosis. *The Tumor Necrosis Factors (TNF)* superfamily of cytokines represents a multifunctional group proinflammatory cytokines, which activate signalling pathways for cell survival, apoptosis, inflammatory responses, and cellular differentiation. Induction of cellular responses to TNF occurs through two receptors, TNFR1 (TNF Receptor-1 or CD120a) and TNFR2 (TNF Receptor-2 or CD120b). TNFR1 is activated in most human tissues by the binding of TNFα. On the other hand, TNFR2 is primarily expressed in immune cells and is

The main TNF is TNF-α, which is produced by neutrophils, activated lymphocytes, macrophages, NK cells and several non-hematopoietic cells. The TNF-α is involved in the normal physiology of the endometrial proliferation in the human endometrium. TNF-α is expressed predominantly in epithelial cells, especially in the secretory phase. The stromal cells stain for TNF-α mostly in the proliferative phase of the menstrual cycle. These data

Some reports found that concentrations of TNF-α in both serum and PF were very high at the early stage of the disease and decreased with the severity of the endometriosis. Moreover, the assessment of TNF-α levels in the PF can be used as a basis for non-surgical

The role of IL-6 in the pathogenesis of endometriosis has been widely studied. IL-6 is a regulator of inflammation and immunity, which may represent a physiological link between the endocrine and immune systems. IL-6 also modulates the secretion of other cytokines, promotes T-cell activation, differentiation of B cells and inhibits the growth of several

The data about IL-6 levels in the PF of patients with endometriosis are controversial. In fact, no statistically significant differences are reported between controls and endometriosis

activated by both TNFα and TNFβ (Kawasaki et al., 2002).

suggest that hormones influence the role of this cytokine.

diagnosis of endometriosis.

human cell lines (Nothnick, 2001).

Endometriosis is supposed to be an autoimmune disorder and many autoantibodies have been proposed as a diagnostic test. A variety of autoantibodies have been detected in endometriosis patients (thyroid peroxidase antibody, IgG anti-laminin-1 antibodies, antiphospholipid antibodies and the novel anti-PDIK1L antibodies). The most commonly reported types are antiendometrial antibodies, autoantibodies against the oxidative-stressinduced, antigens to malondialdehyde-modified low-density lipoprotein (LDL) and oxidized low-density lipoprotein (Ox-LDL).

Some investigators have hypothesized that antiendometrial antibodies may cause infertility in some women with endometriosis by preventing the fertilized embryo from implanting in the uterus. In addition, increasing evidence suggests that oxidative stress occurs in the PF of women with endometriosis and oxidatively modified lipoproteins were found in the PF.
