Utjecaj estrogena na razinu antikardiolipinskih protutijela u bolesnica sa sistemskim eritemskim lupusom [Influence of estrogens on the level of anticardiolipin antibodies in females with systemic lupus erythematosus]

Martinović-Kaliterna, Dušanka (2007) Utjecaj estrogena na razinu antikardiolipinskih protutijela u bolesnica sa sistemskim eritemskim lupusom [Influence of estrogens on the level of anticardiolipin antibodies in females with systemic lupus erythematosus]. PhD thesis, Sveučilište u Zagrebu.

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Abstract

Objective: The aim of this study was to explore the contribution of estrogenic level in systemic lupus erythematosus (SLE) female patients regarding the production of anticardiolipin antibodies by evaluating thrombotic events. The relationship between estrogen level and the titres of C3 and C4 components of complement (particularly in SLE patients with thrombosis) was studied, too. ----- Subjects: 124 female patients who fulfilled the SLE criteria with a mean age 33±7 years were selected. The blood samples were tested for E2, aCL, C3, C4 between the 14th-16th day of the menstrual cycle. The patients were clinically evaluated and the thrombotic events if emerged were noted. 60 healthy women of the same age were selected for the control group. ----- Methods: Estrogen-estradiol was tested by radioimmunoassay method during the menstrual period. Anticardiolipin antibodies were measured by ELISA, and the results were expressed in GPL, MPL and APL units, which equal 1µ/ml affinity of purified antibody. The testing of complement's compounds was performed by nephelometry using standard Behring antiserum N on human C3 and C4. ----- Results: A significant relationship between E2 and IgM aCL-a (p<0.001), and between E2 and IgG aCL-a (p=0.007) were proven. There was no significant correlation between E2 and complement's compounds as well as between E2 and IgA aCL. The SLE patients depending on the thrombotic event were divided into two groups: with APS (n=39) and without APS (n=85). In patients with APS, comparing with those with no APS, the estrogen levels were markedly higher (p=0.009), as were the levels of IgG aCL (p<0.001) and the levels of IgM aCL (p=0.002), while the C3 levels (p<0.001) and C4 levels (p=0.007) were significantly lower. ----- Conclusion: In the group of 124 patients with SLE the positive significant correlation between estrogens and anticardiolipin antibodies IgG and IgM was proved (the estrogen stimulates the production of aCL!). Further, estrogen levels were significantly higher in the group of patients with secondary APS when compared to the group without APS (the important role estrogens in the thrombotic events in SLE!). The titres of C3 and C4 were also significantly lower in SLE patients with APS (the result of excessive complement activation due to the thrombotic event?!).

Abstract in Croatian

Cilj: Ovim istraživanjem se nastojalo utvrditi koliko povišene razine estrogena u SLE-u utiču na stvaranje antikardiolipinskih protutijela i razvoj tromboembolija u sklopu pridruženog APS-a. Pored toga ispitivana je i ovisnost komponenti komplementa o estrogenu u SLE-u, naročito u ispitanica s tromboembolijama. ----- Ispitanice: U radu su ispitivane 124 SLE bolesnice, prosječne životne dobi 33±7 godina. Kod ispitanica je praćena pojavnost tromboembolijskih zbivanja. Uzorak krvi je uziman 14-og do 16-og dana menstrualnog ciklusa: određivane su razine estradiola, antikardiolipinskih protutijela, komponenti C3 i C4 komplementa. Isti parametri su praćeni u 60 zdravih ispitanica u istom intervalu menstrualnog ciklusa. ----- Metode: Estrogen-estradiol je određivan metodom radioimunotesta. Antikardiolipinska protutijela određivana su metodom ELISA-e, rezultati su izraženi u GPL, MPL i APL jedinicama, što odgovara 1µ/ml afiniteta pročišćenog protutijela. Komponente komplementa određivane su nefelometrijski uz korištenje standardnog Behringov-ovog antiseruma N na humane komponente C3 i C4. ----- Rezultati: Praćenjem povezanosti estrogena s ispitivanim varijablama potvrđena je značajna povezanost E2 i IgM aCL-a (p<0,001), kao i IgG aCL-a (p=0,007),dok nije potvrđena povezanost E2 i komplementa, kao ni E2 i IgA aCL-a. Ovisno o prisutnosti tromboembolijskih zbivanja ispitanice su podijeljene u dvije skupine: u skupinu s APS-om (n=39) i u skupinu bez APS-a (N=85). U skupini s APS-om u odnosu na skupinu bez APS-a potvrđene su značajno više razine estradiola (p=0,009), uz više razine IgG aCL-a( p<0,001), kao i IgM aCL-a (p=0,002). Osim toga, u skupini s APS-om potvrđene su i značajno niže razine C3 (p<0,001) i C4 (p=0,007). ----- Zaključak: U skupini od 124 ispitanice sa SLE-om potvrđena je pozitivna korelacija estrogena i antikardiolipinskih protutijela IgG i IgM (estrogeni potiču stvaranje antikardiolipinskih protutijela!). U ispitanica s prisutnim APS-om potvrđene su značajno više razine estrogena uz paralelno više razine IgG aCL-a i IgM aCL-a u odnosu na ispitanice bez APS-a (važna uloga estrogena u tromboembolijama u SLE-u!). Značajno niže razine C3 i C4 u ispitanica s APS-om u odnosu na one bez APS-a nisu pod uplivom estrogena (posljedica povećane potrošnje komplementa uslijed tromboembolijskih događanja?!).

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