Anti-laminin-1 Autoantibodies, Pregnancy Loss and Endometriosis英文文献资料.docVIP

ClinicalDevelopmentalImmunology,September/December2004,Vol.11(3/4),pp.261–266 Anti-laminin-1Autoantibodies,PregnancyLoss andEndometriosis JUNKOINAGAKIa,AKANEKONDOa,b,LUISR.LOPEZc,YEHUDASHOENFELDdandEIJIMATSUURAa,* aDepartmentofCellChemistry,OkayamaUniversityGraduateSchoolofMedicineandDentistry,2-5-1Shikata-cho,Okayama700-8558,Japan; bDepartmentofObstetricandGynecology,TokaiUniversity,Isehara,Japan; cCorgenixInc.,Westminster,CO,USA; dDepartmentofMedicineB andCenterforAutoimmuneDiseases,ShebaMedicalCenter,Tel-Hashomer,Israel. Laminin-1 is a major component and multifunctional glycoprotein of basement membranes that consistsofthreedifferentsubunits,a1,b1andg1chains.Itistheearliestsynthesizednetwork-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 signi?cantly associated with recurrent ?rst-trimester miscarriages and with subsequent pregnancy outcome.Interestingly,theseantibodieswerealsoobservedinpatientswithendometriosis-associated infertility but not in patients with other causes of infertility, including tubal factors, hormonal and uterineabnormalities.Laminin-a1,-b1and-g1mRNAshavebeendetectedin90%ofendometriotic lesionsandalllaminin-a1,-b1and-g1chainswerelocalizedinthebasementmembranesofglandular epithelium in endometriotic peritoneal lesions. Western blot analysis showed that anti-laminin-1 antibodiesfromthosepatientsreactedwithalllaminin-1’schains.ELISAalsocon?rmedthatoneofthe targetepitopesfortheseantibodieswaslocatedinaparticularregionofthelaminin-1molecule,i.e.the carboxyl-terminalglobularGdomainofa1chain.IgMmonoclonalanti-laminin-1autoantibody,that we recently established, also recognized the G domain. Anti-laminin-1 antibodies from mice immunizedwith“mouse”laminin-1,causedahigherfetalresorptionratewithlowerembryonicand placentalweights.Thus,anti-laminin-1antibodiesmaybeimportantindevelopmentofautoimmune- m