Pregnancy in a heart transplant recipient with history of severe humoral and cellular rejection and positive donor-specific antibodies – case report

    Authors

    Keywords

    heart transplantation, pregnancy, donor-specific antibodies

    DOI

    https://doi.org/10.15836/ccar2023.298

    Full Text

    **Background**: Pregnancy in heart transplant (HT) recipients with episodes of rejection or positive donor specific antibodies (DSA) is discouraged by all recommendations due to higher risk of complications. Although there is paucity of data for DSA trend during pregnancy in HT recipients, there is evidence of improvement of symptoms during pregnancy in some autoimmune diseases (1-3). **Case report**: 23-year-old female who underwent HT due to post-myocarditis cardiomyopathy in June 2014, reported unplanned pregnancy in June 2022. She had a history of acute cellular (3R/3B) and humoral rejection (DSA major histocompatibility complex (HLA) class I, specificity A11, A30, B13, B35 and HLA class II, specificity DR3, DR15, DR51, DR52, DQ2, mean fluorescent intensity (MFI) 1000-13 300) in August 2017 which required mechanical circulatory support due to severe heart failure with multiorgan damage. She underwent pulse corticosteroid treatment, and 12 cycles of plasmapheresis with administration of rituximab, intravenous immunoglobulins, and thymoglobulin. After that she had persistent positive DSA, predominantly DQ2 (MFI up to 12200), and because of that was on quadruple immunosuppression (tacrolimus, mycophenolate (MMF), everolimus, prednisone) from October 2019 to July 2020 when MMF was discontinued due to gastrointestinal side effects. She had one more cellular rejection episode (2R/3A) in March 2022 which was treated with pulse corticosteroids. During pregnancy she was on tacrolimus, everolimus, and prednisone combination with closely monitoring of immunosuppressants concentrations. Echocardiography controls showed normal left ventricle function and mildly reduced right ventricle function, NT-proBNP was slightly elevated (493-823 ng/L) and DSA were in a downward trend which is shown in **Figure 1**. At 32+3 weeks of pregnancy, she was hospitalized due to early labor. The following day male baby was delivered by Caesarean section due to pathological cardiotocography (Apgar score 8/9). After delivery DSA remained weakly positive. FIGURE 1. Trend in donor specific antibodies (DSA) detected by the Luminex method from September 2017 to May 2023 expressed in mean fluorescent intensity (MFI). The patient had her first episode of humoral and cellular rejection in August 2017, and the second in March 2022. She was on quadruple immunosuppression (tacrolimus, mycophenolate, everolimus, prednisone) from October 2019 to July 2020. She was pregnant from June 2022 to February 2023. **Conclusion**: Although pregnancy in HT recipients with history of rejection and positive DSA is discouraged, positive outcome is possible with close monitoring of multidisciplinary team. Furthermore, we described a rare case of downward trend of positive DSA during pregnancy.

    Literature

    1. Punnoose LR, Coscia LA, Armenti DP, Constantinescu S, Moritz MJ. Pregnancy outcomes in heart transplant recipients. J Heart Lung Transplant. 2020 May;39(5):473–80. https://doi.org/10.1016/j.healun.2020.02.005
    2. Defilippis EM, Kittleson MM. Pregnancy after Heart Transplantation. J Card Fail. 2021 February;27(2):176–84. https://doi.org/10.1016/j.cardfail.2020.07.011
    3. Piccinni MP, Lombardelli L, Logiodice F, Kullolli O, Parronchi P, Romagnani S. How pregnancy can affect autoimmune diseases progression? Clin Mol Allergy. 2016 September 15;14:11. https://doi.org/10.1186/s12948-016-0048-x
    Cardiologia Croatica
    Back to search

    Pregnancy in a heart transplant recipient with history of severe humoral and cellular rejection and positive donor-specific antibodies – case report

    Extended Abstract
    Issue11-12
    Published
    Pages298-289
    PDF via DOIhttps://doi.org/10.15836/ccar2023.298
    heart transplantation
    pregnancy
    donor-specific antibodies

    Authors

    Dubravka Šipuš*ORCIDUniversity of Zagreb School of Medicine, Zagreb, Croatia
    Mia Dubravčić DošenORCIDUniversity of Zagreb School of Medicine, Zagreb, Croatia
    Petra MjehovićORCIDUniversity of Zagreb School of Medicine, Zagreb, Croatia
    Dora FabijanovićORCIDUniversity of Zagreb School of Medicine, Zagreb, Croatia
    Nina JakušORCIDUniversity of Zagreb School of Medicine, Zagreb, Croatia
    Ivo PlanincORCIDUniversity of Zagreb School of Medicine, Zagreb, Croatia
    Marijan PašalićORCIDUniversity of Zagreb School of Medicine, Zagreb, Croatia
    Hrvoje JurinORCIDUniversity of Zagreb School of Medicine, Zagreb, Croatia
    Jure SamardžićORCIDUniversity of Zagreb School of Medicine, Zagreb, Croatia
    Daniel LovrićORCIDUniversity of Zagreb School of Medicine, Zagreb, Croatia
    Maja ČikešORCIDUniversity of Zagreb School of Medicine, Zagreb, Croatia
    Hrvoje GašparovićORCIDUniversity of Zagreb School of Medicine, Zagreb, Croatia
    Renata ŽunecORCIDUniversity of Zagreb School of Medicine, Zagreb, Croatia
    Davor MiličićORCIDUniversity of Zagreb School of Medicine, Zagreb, Croatia
    Vesna Elveđi GašparovićORCIDUniversity of Zagreb School of Medicine, Zagreb, Croatia
    Boško SkorićORCIDUniversity of Zagreb School of Medicine, Zagreb, Croatia

    *Correspondence email: dubravka.sipus@gmail.com

    Full Text

    Background: Pregnancy in heart transplant (HT) recipients with episodes of rejection or positive donor specific antibodies (DSA) is discouraged by all recommendations due to higher risk of complications. Although there is paucity of data for DSA trend during pregnancy in HT recipients, there is evidence of improvement of symptoms during pregnancy in some autoimmune diseases (1–3).

    Case report: 23-year-old female who underwent HT due to post-myocarditis cardiomyopathy in June 2014, reported unplanned pregnancy in June 2022. She had a history of acute cellular (3R/3B) and humoral rejection (DSA major histocompatibility complex (HLA) class I, specificity A11, A30, B13, B35 and HLA class II, specificity DR3, DR15, DR51, DR52, DQ2, mean fluorescent intensity (MFI) 1000-13 300) in August 2017 which required mechanical circulatory support due to severe heart failure with multiorgan damage. She underwent pulse corticosteroid treatment, and 12 cycles of plasmapheresis with administration of rituximab, intravenous immunoglobulins, and thymoglobulin. After that she had persistent positive DSA, predominantly DQ2 (MFI up to 12200), and because of that was on quadruple immunosuppression (tacrolimus, mycophenolate (MMF), everolimus, prednisone) from October 2019 to July 2020 when MMF was discontinued due to gastrointestinal side effects. She had one more cellular rejection episode (2R/3A) in March 2022 which was treated with pulse corticosteroids. During pregnancy she was on tacrolimus, everolimus, and prednisone combination with closely monitoring of immunosuppressants concentrations. Echocardiography controls showed normal left ventricle function and mildly reduced right ventricle function, NT-proBNP was slightly elevated (493-823 ng/L) and DSA were in a downward trend which is shown in Figure 1. At 32+3 weeks of pregnancy, she was hospitalized due to early labor. The following day male baby was delivered by Caesarean section due to pathological cardiotocography (Apgar score 8/9). After delivery DSA remained weakly positive.

    FIGURE 1. Trend in donor specific antibodies (DSA) detected by the Luminex method from September 2017 to May 2023 expressed in mean fluorescent intensity (MFI). The patient had her first episode of humoral and cellular rejection in August 2017, and the second in March 2022. She was on quadruple immunosuppression (tacrolimus, mycophenolate, everolimus, prednisone) from October 2019 to July 2020. She was pregnant from June 2022 to February 2023.

    Conclusion: Although pregnancy in HT recipients with history of rejection and positive DSA is discouraged, positive outcome is possible with close monitoring of multidisciplinary team. Furthermore, we described a rare case of downward trend of positive DSA during pregnancy.

    Literature

    1. 1.
      Punnoose LR, Coscia LA, Armenti DP, Constantinescu S, Moritz MJ. Pregnancy outcomes in heart transplant recipients. J Heart Lung Transplant. 2020 May;39(5):473–80.DOI
    2. 2.
      Defilippis EM, Kittleson MM. Pregnancy after Heart Transplantation. J Card Fail. 2021 February;27(2):176–84.DOI
    3. 3.
      Piccinni MP, Lombardelli L, Logiodice F, Kullolli O, Parronchi P, Romagnani S. How pregnancy can affect autoimmune diseases progression? Clin Mol Allergy. 2016 September 15;14:11.DOI