Anti-laminin-1 autoantibodies, pregnancy loss and endometriosis

Abstract

Laminin-1 is a major component and multifunctional glycoprotein of basement membranes that consists of three different subunits, a1, b1 and g1 chains. It is the earliest synthesized network-forming protein during embryogenesis and plays an important role in embryonic development, embryonic implantation and placentation. We have recently shown that IgG anti-laminin-1 antibodies were significantly associated with recurrent first-trimester miscarriages and with subsequent pregnancy outcome. Interestingly, these antibodies were also observed in patients with endometriosis-associated infertility but not in patients with other causes of infertility, including tubal factors, hormonal and uterine abnormalities. Laminin-a1, -b1 and -g1 mRNAs have been detected in 90% of endometriotic lesions and all laminin-a1, -b1 and -g1 chains were localized in the basement membranes of glandular epithelium in endometriotic peritoneal lesions. Western blot analysis showed that anti-laminin-1 antibodies from those patients reacted with all laminin-1's chains. ELISA also confirmed that one of the target epitopes for these antibodies was located in a particular region of the laminin-1 molecule, i.e. the carboxyl-terminal globular G domain of a1 chain. IgM monoclonal anti-laminin-1 autoantibody, that we recently established, also recognized the G domain. Anti-laminin-1 antibodies from mice immunized with "mouse" laminin-1, caused a higher fetal resorption rate with lower embryonic and placental weights. Thus, anti-laminin-1 antibodies may be important in development of autoimmunemediated reproductive failures and the assessment of the antibodies may provide a novel non-invasive diagnosis of endometriosis.

Basement membranes and autoimmune diseases

“…Anti-laminin antibodies are detected in murine and human SLE, including among a subset of crossreactive anti-DNA Ig, and may mediate BM binding [199–202]. Anti-laminin autoantibodies have been associated with Raynaud’s phenomenon, cardiomyopathy, pregnancy loss, and psoriasis in man [203–205]. Pathogenic potential of anti-laminin IgG is suggested by induction of proteinuria and glomerular BM alterations in rats after passive transfer of anti-laminin Ig [206], and by the ability of laminin peptides to suppress lupus nephritis in MRL/lpr mice [207].…”

Attachment to laminin-111 facilitates transforming growth factor -induced expression of matrix metalloproteinase-3 in synovial fibroblasts

“…18 In humans, elevated LM-111 expression was described in endometriotic lesions and anti-LM-111 autoantibodies were found in infertile patients. 19 Enhanced expression of LM-111 was also reported in astrocytes of diseased areas in the frontal cortex of Alzheimer's brain tissues, 20 and reduced expression was observed in acinar basement membranes of patients with Sjögren's syndrome, 21 indicating that LM expression patterns change during pathological processes.…”

Anti-Laminin-1 Antibodies in Sera and Follicular Fluid of Women with Endometriosis Undergoing in Vitro Fertilization

“…Among the various auto-Abs described (9)(10), recently aLN-1 have gained more attention due to their significantly higher prevalence in patients with endometriosis when compared with infertile patients without endometriosis (11). It has been suggested that aLN-1 affect early reproductive processes, leading to autoimmune-mediated infertility (12)(13).…”