1. Long-term outcome of LRBA deficiency in 76 patients after various treatment modalities as evaluated by the immune deficiency and dysregulation activity (IDDA) score
- Author
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Bella Shadur, Andrew R. Gennery, Nurcicek Padem, Anna Mukhina, Polina Stepensky, Svetlana O. Sharapova, Sara Sebnem Kilic, Magdalena Avbelj Stefanija, Luis I. Gonzales-Granado, Isabelle Meyts, Jacques G. Rivière, Filomeen Haerynck, Joachim Zobel, Benoit Florkin, Laura Gamez, Vedat Uygun, Nicolette Moes, Neslihan Edeer Karaca, Lennart Hammarström, Anke M.J. Peters, Bodo Grimbacher, Sevgi Köstel Bal, Aydan Ikinciogullari, Zahra Chavoshzadeh, Joris M. van Montfrans, Sule Haskologlu, Hassan Abolhassani, Necil Kutukculer, Safa Baris, Yuliya Mareika, Juan Luis Santos Perez, Elif Karakoc-Aydiner, Asghar Aghamohammadi, Mehdi Adeli, Antonio Marzollo, Hermann J. Girschick, Sevgi Keles, Amer Khojah, Shahrzad Bakhtiar, Victoria Katharina Tesch, Anna Shcherbina, Antonios G.A. Kolios, Marie Meeths, Mikko Seppänen, Austen Worth, Marina Garcia-Prat, Figen Dogu, Arjan C. Lankester, Markus G. Seidel, European Soc Blood, European Soc Immunodeficiencies, University of Zurich, Tesch, Victoria Katharina, Abolhassani, Hassan, Shadur, Bella, Zobel, Joachim, Mareika, Yuliya, Sharapova, Svetlana, Karakoc-Aydiner, Elif, Riviere, Jacques G., Garcia-Prat, Marina, Moes, Nicolette, Haerynck, Filomeen, Gonzales-Granado, Luis I., Santos Perez, Juan Luis, Mukhina, Anna, Shcherbina, Anna, Aghamohammadi, Asghar, Hammarstrom, Lennart, Dogu, Figen, Haskologlu, Sule, Ikinciogullari, Aydan I., Bal, Sevgi Kostel, Baris, Safa, Kilic, Sara Sebnem, Karaca, Neslihan Edeer, Kutukculer, Necil, Girschick, Hermann, Kolios, Antonios, Keles, Sevgi, Uygun, Vedat, Stepensky, Polina, Worth, Austen, van Montfrans, Joris M., Peters, Anke M. J., Meyts, Isabelle, Adeli, Mehdi, Marzollo, Antonio, Padem, Nurcicek, Khojah, Amer M., Chavoshzadeh, Zahra, Stefanija, Magdalena Avbelj, Bakhtiar, Shahrzad, Florkin, Benoit, Meeths, Marie, Gamez, Laura, Grimbacher, Bodo, Seppanen, Mikko R. J., Lankester, Arjan, Gennery, Andrew R., Seidel, Markus G., Ege Üniversitesi, Bursa Uludağ Üniversitesi/Tıp Fakültesi/Çocuk İmmünoloji., Kılıç, Sara Şebnem, AAH-1658-2021, Children's Hospital, HUS Children and Adolescents, Clinicum, Department of Medicine, TRIMM - Translational Immunology Research Program, Research Programs Unit, University of Helsinki, and HUS Inflammation Center
- Subjects
Male ,Neurologic disease ,medicine.medical_treatment ,Autoimmunity ,Hematopoietic stem cell transplantation ,Treatment response ,Eye disease ,0302 clinical medicine ,Thrombotic thrombocytopenic purpura ,Azathioprine ,combined immunodeficiency ,Disease activity ,Treatment outcome ,Disease course ,Child ,Inborn error of immunity (IEI) ,Immunodeficiency ,combined ,Hematopoietic Stem Cell Transplantation ,combined immunodeficiency (CID) ,hematopoietic stem cell transplantation (HSCT) ,Tocilizumab ,Signal transducing ,Multicenter study ,Immunologic deficiency syndromes ,3. Good health ,Clinical trial ,Retrospective study ,sirolimus ,Child, Preschool ,Cyclosporine ,2723 Immunology and Allergy ,Graft failure ,Lung infection ,hematopoietic stem ,Cohort analysis ,Longitudinal study ,Rituximab ,Infection ,Human ,Hepatomegaly ,medicine.medical_specialty ,Genotype ,Immunology ,Cause of death ,Major clinical study ,Article ,03 medical and health sciences ,Signal transducing adaptor protein ,Humans ,Lipopolysaccharide responsive beige like anchor protein deficiency ,cell transplantation ,Aged ,2403 Immunology ,MUTATIONS ,Abatacept ,Immunologic Deficiency Syndromes ,Adalimumab ,Failure to thrive ,Follow up ,Survival analysis ,Immune dysregulation ,medicine.disease ,Survival Analysis ,030104 developmental biology ,Disease activity score ,Splenomegaly ,10033 Clinic for Immunology ,School child ,Human medicine ,immunodeficiency ,0301 basic medicine ,Thyroiditis ,Allergy ,Unclassified drug ,Immune deficiency ,Lipopolysaccharide responsive beige like anchor protein ,Respiratory failure ,Skin manifestation ,medicine.disease_cause ,Lymphocyte proliferation ,Medicine and Health Sciences ,Immunology and Allergy ,Overall survival ,Middle aged ,performance scale ,Interstitial pneumonia ,Priority journal ,CTLA4 ,Mycophenolate mofetil ,Chloroquine ,clinical score ,Immunosuppression ,Disease burden ,Transplant-Related Mortality ,Middle Aged ,Acute graft versus host disease ,Hospitalization ,Immune deficiency and dysregulation activity score ,Treatment Outcome ,Phenotype ,surgical procedures, operative ,primary immunodeficiency disorder (PID) ,hematopoietic stem cell transplantation ,Female ,medicine.drug ,Adult ,dysregulation ,Malabsorption ,abatacept ,Adolescent ,Child, preschool ,Pemission ,Interstitial lung disease ,610 Medicine & health ,LRBA ,Young Adult ,immune dysregulation ,Internal medicine ,Adaptor proteins ,medicine ,primary immunodeficiency disorder ,Mycophenolic acid ,Rapamycin ,Mortality ,Disease severity ,Adaptor Proteins, Signal Transducing ,Inborn error of immunity ,Chimera ,business.industry ,Protein ,Retrospective cohort study ,LRBA protein ,Multiple organ failure ,Infliximab ,Immunosuppressive treatment ,Young adult ,Preschool child ,3121 General medicine, internal medicine and other clinical medicine ,Common Variable Immunodeficiency ,Immunoglobulin Deficiency ,immune ,business ,030215 immunology - Abstract
Background: Recent findings strongly support hematopoietic stem cell transplantation (HSCT) in patients with severe presentation of LPS-responsive beige-like anchor protein (LRBA) deficiency, but long-term follow-up and survival data beyond previous patient reports or meta-reviews are scarce for those patients who do not receive a transplant. Objective: This international retrospective study was conducted to elucidate the longitudinal clinical course of patients with LRBA deficiency who do and do not receive a transplant. Method: We assessed disease burden and treatment responses with a specially developed immune deficiency and dysregulation activity score, reflecting the sum and severity of organ involvement and infections, days of hospitalization, supportive care requirements, and performance indices. Results: of 76 patients with LRBA deficiency from 29 centers (median follow-up, 10 years; range, 1-52), 24 underwent HSCT from 2005 to 2019. the overall survival rate after HSCT (median follow-up, 20 months) was 70.8% (17 of 24 patients); all deaths were due to nonspecific, early, transplant-related mortality. Currently, 82.7% of patients who did not receive a transplant (43 of 52; age range, 3-69 years) are alive. of 17 HSCT survivors, 7 are in complete remission and 5 are in good partial remission without treatment (together, 12 of 17 [70.6%]). in contrast, only 5 of 43 patients who did not receive a transplant (11.6%) are without immunosuppression. Immune deficiency and dysregulation activity scores were significantly lower in patients who survived HSCT than in those receiving conventional treatment (P = .005) or in patients who received abatacept or sirolimus as compared with other therapies, and in patients with residual LRBA expression. Higher disease burden, longer duration before HSCT, and lung involvement were associated with poor outcome. Conclusion: the lifelong disease activity, implying a need for immunosuppression and risk of malignancy, must be weighed against the risks of HSCT., Styrian Children's Cancer Aid Foundation; Slovenian Research AgencySlovenian Research Agency - Slovenia [P3-0343]; Jonas S_oderquist Foundation; Scientific and Technological Research Council of TurkeyTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [217S847, 318S202]; Deutsche Forschungsgemeinschaft under Germany's Excellence StrategyGerman Research Foundation (DFG) [390939984, 39087428]; E-Rare program of the European Union by the Deutsche ForschungsgemeinschaftGerman Research Foundation (DFG) [GR1617/14-1/iPAD]; Netzwerke Seltener Erkrankungen of the German Ministry of Education and Research [GAIN_ 01GM1910A]; Finnish Foundation for Pediatric Research and Pediatric Research Center, HUS Helsinki University Hospital; Graduate Research Training Scholarship of the Australian government; Hadassah Australia; ERN-RITA network [739543], M.G. Seidel and the Research Unit for Pediatric Hematology and Immunology are supported in part by the Styrian Children's Cancer Aid Foundation. M. Avbeli Stefanija was supported by the Slovenian Research Agency (grant P3-0343). H. Abolhassani was supported by the Jonas S_oderquist Foundation. S. Baris was supported by the Scientific and Technological Research Council of Turkey for the diagnosis of patients with LRBA deficiency (grants 217S847 and 318S202). B. Grimbacher receives support through the Deutsche Forschungsgemeinschaft under Germany's Excellence Strategy (CIBSS-EXC-2189-Project ID 390939984 and RESIST-EXC 2155-Project ID 39087428); through the E-Rare program of the European Union, managed by the Deutsche Forschungsgemeinschaft (grant GR1617/14-1/iPAD); and through the Netzwerke Seltener Erkrankungen of the German Ministry of Education and Research (grant GAIN_ 01GM1910A). M.R.J. Sepp_anen was supported by the Finnish Foundation for Pediatric Research and Pediatric Research Center, HUS Helsinki University Hospital. I. Meyts is a member of the ERN-RITA network (project identification number 739543). B. Shadur is supported by a Graduate Research Training Scholarship of the Australian government and by Hadassah Australia.
- Published
- 2020