adamianis qorionuli gonadotropinis (aqg) winaaRmdeg mimarTuli autoantisxeulebi reproduqciuli sistemis avTvisebiani da keTilTvisebiani simsivniT daavadebulebSi.

 

l.axvlediani, n.foraqiSvili, o.Caxoiani, j.qiqava.

 

baTumis saxelmwifo universiteti, Tbilisis saxelmwifo universiteti, baTumis mezRvaurTa samedicino centri.

 

 reziume

 

   Cvens mier miRebuli monacemebiT keTilTvisebiani simsivniT daavadebulebSi (sakvercxis histoma, endometriumis polipi,saSvilosnos fsevdomucinozuri kista) anti-hCG antisxeulebis Semcveloba sisxlis SratSi ufro maRal maCvenebels iZleva avTvisebiani simsivnis mqone gamokvleul pirebTan SedarebiT (saSvilosnos tanis kibo, saSvilosnos yelis kibo,sakvercxis kibo) es SesaZlebelia miuTiTebs imaze, rom specifiuri antisxeulebis produqcia moqmedebs hCG-is neitralizaciaze da amitomac aferxebs simsivneTa  zrdis efeqts. Cveni  mosazrebiT   anti-hCG antisxeulebis aRmoCena SesaZlebelia gamodges araavTvisebiani simsivneebis diferencialuri diagnozisaTvis.

 

Sesavali

 

   adamianis qorionuli gonadotropini (aqg) glikoproteinul hormonTa ojaxis wevria. igi Sedgeba arakovalenturad dakavSirebuli suberTeulebisagan.Tavisufali hCGα  da hCG β cilebi  kodirdeba ramdenime damoukidebeli geniT [1,4,9,10].  glikoproteinul hormonTa ojaxSi Sedis aseve maluTeinizirebeli Hhormoni(LH), folikulmastimulirebeli hormonida Tiroid-mastimulirebeli hormoni. yoveli maTgani warmodgenilia αβ heterodimeris saxiT[2].  qg danarCeni hormonebisagan imiTgansxvavdeba, rom igi sinTezirdeba placentas trofoblasturi ujredebis mier ganayofierebis Semdeg da misi aRmoCena SratSi SesaZlebelia orsulobis dros. qg-is zemoqmedebiT  yviTeli sxeuli asinTezirebs iseTi raodenobiT progesterons, rom ar xdeba endometriumis ukugdeba da narCundeba orsuloba. amis garda nativuri glikoproteini da suberTeulebi aseve sinTezirdeba trofoblasturi da aratrofoblasturi warmoSobis malignizirebadi ujredebis mier [8]. gamokvlevebma aCvena, rom aratrofoblasturi simsivnis mqone pirebSi xSirad  Tavisufali  hCG β-is done SratSi aRwevs 100pg/ml-s[6,9].  Tavisufali  hCG β-s deteqcia  SratSi ufro meti sixSiriT (30%-40%) gvxvdeba saSarde buStis, pakreasis, saSvilosnos yelis simsivneebis dros [6]. amitom Tavisufali  hCG β-s deteqcia SratSi, gansakuTrebiT mamakacebSi, SeiZleba CaiTvalos  simsivneasocirebul markerad da misi aRmoCena miuTiTebs daavadebis cud prognozze.

   simsivneebis dros SratSi hCG-is eqspresia SesaZlebelia ZiriTad rols TamaSobdes specifiuri  autoantisxeulebis gamomuSavebaSi, rac saukeTeso serologiuri markeria.

 

 

 

masala da meTodi

 

 

 

   Cven gamovikvlieT 10 saSvilosnos tanis kiboTi daavadebulis, 10 sakvercxis kiboT daavadebulis, 10 endometriumis polipis mqone, 6 saSvilisnos yelis kiboTi daavadebulis, da 5 sakvercxis histomis mqone pirTa  periferiuli sisxlis Srati. gamokvleul pirTa asaki iyo 35-68 wlamde.

 

   kvlevis mizans warmoadgenda adamianis qorionuli gonadotropinis mimarT  autoantisxeulebis titris dadgena arapirdapiri imunofermentuli analiziT.

 

   96 fosoian brtyelZirian planSetebze vaxdendiT 50 mkl hCG  (SIGMA)  datanebas 1mg/ml koncentraciiT karbonat-bikarbonatul buferSi da vainkubirebdiT 24sT. 4 gradusze. planSets vrecxavdiT fosfaturi buferiT, romelic Seicavda 0,05% Tvin-20-s (SIGMA).

     Semdgom  fosoebSi vasxamdiT sakvlev Srats, ganzavebuls tvinisa da 2% xaris Sratis albuminis Semcveli fosfaturi buferiT  (SIGMA). sakvlev Srats vanzavebdiT 1:25, 1:50, 1:100, 1:200, 1:400, 1:800, 1:1600, 1:3200,  1:6400, 1:12800–jer.

   koniugatis saxiT viyenebdiT Tagvis anti-adamianis IgG-s,romelsac vamatebdiT yvela fosoSi optimaluri titriT1:100.

   substrates saxiT viyenebdiT 10 mlg p-nitrofenil fosfatids, romelsac vxsnidiT 100mkl MgCI2-is Semcvelkarbonat-bikarbonatul buferSi. reaqcias vaCerebdiT 12% -iani  gogirdmJavaTi.

   optikur simkvrives vsazRvravdiT multiskan MCC-ze, talRis sigrZe-405 nm.

 

 

 

 

 

 

 

 

 

 

Sedegebi

 

  anti-hCG antisxeulebis titri gamokvleul pacientebSi naCvenebia #1,2,3 suraTebze. yvelaze maRali titri anti-hCG antisxeulebisa aRmoaCndaT  sakvercxis  histomiT daavadebul  da saSvilosnos  fsevdomucinozuri kistis mqone pirebSi.  1 : 25 ganzavebisas autoantisxeulebis titri  pirvel SemTxvevaSi tolia 1,126 ;xolo meore SemTxvevaSi  ki-2-is.

   yvelaze dabali maCveneneblebiT xasiaTdeboda saSvilosnos tanis da sakvercxis kibos mqone pacientTa sisxlis Srati (sur. #2 da3).  yvelaze maRali maCvenebeli saSvilosnos tanis kibos SemTxvevaSi aRwevda 0,959-s, xolo sakvercxis kibos SemTxvevaSi anti-hCG autoantisxeulebis titri kidev ufro dabali iyo (0,4) . amasTan rac ufro maRali iyo simsivnis stadia miT ufro Ddabali iyo anti-hCG antisxeulebis titri. e. i. anti-hCG antisxeulebis raodenobis SemcirebasTan erTad izrdeboda simsivnis agresiuloba.  es SesaZlebelia miuTiTebs imaze, rom specifiuri antisxeulebis produqcia moqmedebs hCG  neitralizaciaze da amitom  keTilTvisebiani simsivneebis  SemTxvevaSi  anti-hCG antisxeulebi aferxeben simsivneTa zrdis efeqts

    rasakvirvelia hCG ZiriTadad sinTezirdeba trofoblasturi ujredebis mier orsulobis SesanarCuneblad. es glikoproteini aseve sinTezirdeba malignizirebuli ujredebis mier rogorc trofoblasturi aseve ara trofoblasturi simsivneebis dros.

    hCG-is Tavisufali β suberTeuli farTod gamoiyeneba, rogorc daunis sindromis markeri [11,3] ,aseve warmoadgens zogi epiTeluri simsivnis prognozirebad markers [5].  ufro metic hCG-is SratSi aRmoCena SesaZlebelia reproduqciuli sistemis simsivneebis dros. am SemTxvevaSi, orsulobisagan gansxvavebiT hCG sinTezirdeba simsivnuri ujredebis mier ufro meti vidre Tavisufali hCGβ. aris imis mtkicebuleba,  rom hCGβ TamaSobs simsivnis zrdis mastimulirebeli hormonis rols. Tavisufali hCGβ-s eqspresia solidur simsivneebTan miuTiTebs mis agresiulobaze,maRal metastazirebad potencialsa da swraf zrdaze[7]. sisxlis cirkulaciaSi  yofnisas hCGβ molekulebis umetesoba  simsivnis zrdis procesSi iwvevs organizmis imunizacias da anti-hCG antisxeulebis  gamomuSavebas, rac warmoadgens Cveni kvlevis mizans.

 

 

 

                                                                                                                       

References

 

1.      Boorstein W.R., Vamvakopoulos NK.,and Fiddes JC. (1990). Human chorionic gonadotrophin beta-subunit is encoded by at least eight genes arranjed in tandem and inverted pains. Nature.300;419-422.

2.      Butler S.A. Laider P.,Porter J. R.,KicmanA.T>,Chard T.,Covan D.A. and Iles R.K.,(1999) β-subunit of human chorionic gonadotrophin exists as e homodimer.Journal of  Molecular Endokrinology,22:185-192.

3.      Cucle H.S.Iles RK and chard T.(1994). Urinari βcore hCG a new approach to Dovn’s syndrome screening.Prenatal diagnosis 14;953-958.

4.      FiddesJC and Goodman HM,(1980). The cDNA for β-subunit of human chorionic gonadotrophin suggests evolution of a gene by readthrough into 3’- untranslated region. Nature, 286;684-687.

5.      Iles RK.,Persad R.,Trivedi M.,Sharma KB.,Dickenson A.,Smith P. and Chard T. (1996) Urinari concentration  of hCG and its fragments as a prognostic marker in bladder cancer. British Journal of Urology, 77;61-69.9

6.      Marcillac I. ,Troalen F. ,Bidart  JM. ,Ghillani P, Ribrag V, Escudier B.Mallassagne B, Droz JP, and Bellet D.(199 ) Free human chorionic gonadotrophin beta-subunit  in gonadal and nongonadal neoplasms. Cancer Res 52;3901-3907.

7.      Moutzoauris G, Yannopoulos D, Barbatis C, 91993). Is beta human chorionic gonadotrophin production by transitional cell carcinoma   of the bladder a marker  for aggressive desease and resistanse to chemotherapy? Br.J.Urol.72;807-809.

8.      Pierse JG  and Parsons TF(1981), Glikoprotein hormones;Strukture and function. Annu.Rev Biochem.50;465-495.

9.      Policastro P. Ovitt CE., Hoshina M, Fukuoka H. Boothby MR. and Boime I. (1983)  The beta-subunit of human chorionic gonadotrophin in encoded by multiple genes. J. Biol,Chem. 258;11492-11499.

10.  Porakishvili N. Jakson AM., DE Souza JB, Dalla chiesa M,  Roitt IM, Delves PJ, Lund T. Epitopes of human chorionic gonadotrophin and thear relationship to immunogenisity and cross-reaktivity of beta chain  mutants. Am. J. Repro.Immunol. 11998,40;210-214.

11.  Spenser K. Coombs EJ. MALLARD as AND Milfordvard A, (1992). Free beta human chorionic gonadotrophin in dovn’s syndrome screening;a multicancer study of its role  compared  with other biological markers , Annals of clinical biochemistry 29; 506-518.

 

Abstract

The patient with ovarian histoma  and uterus cista showed the highest  titre of anty-hCG autoantibodies out of the patients studied.The patient with  malignant tumours hed non-appreciable levels of anti-hCG antibodies.

However a correct measurement of the serum hCG β is technically complex which limits its application for tumour screening. the serum expression of hCG in malignancies may lead  to the induction of specific autoantipodies,which can represent a beeter serum marker.In addition it  will demonstrate a possibility of a recognition of the tumor- associated antigens.

sakvercxis histoma

 

sakvercxis kibo

 

 

 

 

saSvilosnos tanis kibo