Sequential Transplantation of UCBSCs and Islet Cells in Children and Adolescents With Monogenic Immunodeficiency T1DM

Overview

This study evaluates the efficacy of sequential transplantation of umbilical cord blood stem cells and islet cells in children with monogenic immunodeficiency type 1 diabetes mellitus. Umbilical cord blood stem cell transplantation will be performed first. Children with stable immune reconstruction will than receive islet cell transplantation.

Full Title of Study: “Sequential Transplantation of Umbilical Cord Blood Stem Cells and Islet Cells in Children and Adolescents With Monogenic Immunodeficiency Type 1 Diabetes Mellitus”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: December 31, 2025

Detailed Description

Monogenic immunodeficiency type 1 diabetes mellitus (T1DM) usually onsets in early age and has a long course of treatment. Because of T cell deficiency, patients are prone to recurrent infection, hemorrhage, sepsis, colitis or complications of diabetes mellitus, which lead to early death. New clinical treatment schemes have been explored and introduced around the world. Sequential transplantation of umbilical cord blood stem cells and islet cells is the latest treatment method for these children. Early treatment of monogenic immunodeficiency T1DM children can avoid disease-related organ toxicity, infection risk associated with chronic immunosuppression, and possible prevention of autoimmune endocrine organ damage. Thus, sequential transplantation of umbilical cord blood stem cells and islet cells is the only possible cure for those patients currently.

Interventions

  • Procedure: Sequential transplantation
    • After successful matching of umbilical cord blood stem cells, patients will receive pretreatment and chemotherapy under protective isolation, followed by thawing and reinfusion of umbilical cord blood stem cells. Immunosuppressive agents will be used for GVHD prevention and anti-infection support will be provided after reinfusion. The status of umbilical cord blood stem cell implantation, immune reconstruction and therapeutic effect will be evaluated. Islet transplantation will be performed in those who meet the conditions. The long-term prognosis will be observed by long-term follow-up.

Arms, Groups and Cohorts

  • Experimental: Interventional
    • Sequential transplantation of umbilical cord blood stem cells and islet cells

Clinical Trial Outcome Measures

Primary Measures

  • Concentration of serum C-peptide
    • Time Frame: from the completion of treatment to 3 months
    • Islet function (concentration of serum C-peptide)
  • Concentration of serum C-peptide
    • Time Frame: from the completion of treatment to 3 years
    • Islet function (concentration of serum C-peptide)

Secondary Measures

  • Concentration of serum C-peptide
    • Time Frame: from the completion of treatment to 6 months
    • Islet function (concentration of serum C-peptide)
  • Concentration of serum C-peptide
    • Time Frame: from the completion of treatment to 9 months
    • Islet function (concentration of serum C-peptide)
  • Concentration of serum C-peptide
    • Time Frame: from the completion of treatment to 12 months
    • Islet function (concentration of serum C-peptide)
  • Concentration of serum C-peptide
    • Time Frame: from the completion of treatment to 15 months
    • Islet function (concentration of serum C-peptide)
  • Concentration of serum C-peptide
    • Time Frame: from the completion of treatment to 18 months
    • Islet function (concentration of serum C-peptide)
  • Concentration of serum C-peptide
    • Time Frame: from the completion of treatment to 21 months
    • Islet function (concentration of serum C-peptide)
  • Concentration of serum C-peptide
    • Time Frame: from the completion of treatment to 24 months
    • Islet function (concentration of serum C-peptide)
  • Concentration of serum C-peptide
    • Time Frame: from the completion of treatment to 27 months
    • Islet function (concentration of serum C-peptide)
  • Concentration of serum C-peptide
    • Time Frame: from the completion of treatment to 30 months
    • Islet function (concentration of serum C-peptide)
  • Concentration of serum C-peptide
    • Time Frame: from the completion of treatment to 33 months
    • Islet function (concentration of serum C-peptide)
  • Concentration of serum insulin
    • Time Frame: from the completion of treatment to 3 months
    • Concentration of serum insulin
  • Concentration of serum insulin
    • Time Frame: from the completion of treatment to 6 months
    • Concentration of serum insulin
  • Concentration of serum insulin
    • Time Frame: from the completion of treatment to 9 months
    • Concentration of serum insulin
  • Concentration of serum insulin
    • Time Frame: from the completion of treatment to 12 months
    • Concentration of serum insulin
  • Concentration of serum insulin
    • Time Frame: from the completion of treatment to 15 months
    • Concentration of serum insulin
  • Concentration of serum insulin
    • Time Frame: from the completion of treatment to 18 months
    • Concentration of serum insulin
  • Concentration of serum insulin
    • Time Frame: from the completion of treatment to 21 months
    • Concentration of serum insulin
  • Concentration of serum insulin
    • Time Frame: from the completion of treatment to 24 months
    • Concentration of serum insulin
  • Concentration of serum insulin
    • Time Frame: from the completion of treatment to 27 months
    • Concentration of serum insulin
  • Concentration of serum insulin
    • Time Frame: from the completion of treatment to 30 months
    • Concentration of serum insulin
  • Concentration of serum insulin
    • Time Frame: from the completion of treatment to 33 months
    • Concentration of serum insulin
  • Concentration of serum insulin
    • Time Frame: from the completion of treatment to 36 months
    • Concentration of serum insulin
  • Fast blood glucose level
    • Time Frame: from the completion of treatment to 3 months
    • Fast blood glucose level
  • Fast blood glucose level
    • Time Frame: from the completion of treatment to 6 months
    • Fast blood glucose level
  • Fast blood glucose level
    • Time Frame: from the completion of treatment to 9 months
    • Fast blood glucose level
  • Fast blood glucose level
    • Time Frame: from the completion of treatment to 12 months
    • Fast blood glucose level
  • Fast blood glucose level
    • Time Frame: from the completion of treatment to 15 months
    • Fast blood glucose level
  • Fast blood glucose level
    • Time Frame: from the completion of treatment to 18 months
    • Fast blood glucose level
  • Fast blood glucose level
    • Time Frame: from the completion of treatment to 21 months
    • Fast blood glucose level
  • Fast blood glucose level
    • Time Frame: from the completion of treatment to 24 months
    • Fast blood glucose level
  • Fast blood glucose level
    • Time Frame: from the completion of treatment to 27 months
    • Fast blood glucose level
  • Fast blood glucose level
    • Time Frame: from the completion of treatment to 30 months
    • Fast blood glucose level
  • Fast blood glucose level
    • Time Frame: from the completion of treatment to 33 months
    • Fast blood glucose level
  • Fast blood glucose level
    • Time Frame: from the completion of treatment to 36 months
    • Fast blood glucose level
  • HbA1c level
    • Time Frame: from the completion of treatment to 3 months
    • HbA1c level
  • HbA1c level
    • Time Frame: from the completion of treatment to 6 months
    • HbA1c level
  • HbA1c level
    • Time Frame: from the completion of treatment to 9 months
    • HbA1c level
  • HbA1c level
    • Time Frame: from the completion of treatment to 12 months
    • HbA1c level
  • HbA1c level
    • Time Frame: from the completion of treatment to 15 months
    • HbA1c level
  • HbA1c level
    • Time Frame: from the completion of treatment to 18 months
    • HbA1c level
  • HbA1c level
    • Time Frame: from the completion of treatment to 21 months
    • HbA1c level
  • HbA1c level
    • Time Frame: from the completion of treatment to 24 months
    • HbA1c level
  • HbA1c level
    • Time Frame: from the completion of treatment to 27 months
    • HbA1c level
  • HbA1c level
    • Time Frame: from the completion of treatment to 30 months
    • HbA1c level
  • HbA1c level
    • Time Frame: from the completion of treatment to 33 months
    • HbA1c level
  • HbA1c level
    • Time Frame: from the completion of treatment to 36 months
    • HbA1c level
  • occurrence of infection (number of infections)
    • Time Frame: from the completion of treatment to 3 months
    • occurrence of infection (number of infections)
  • occurrence of infection (number of infections)
    • Time Frame: from the completion of treatment to 6 months
    • occurrence of infection (number of infections)
  • occurrence of infection (number of infections)
    • Time Frame: from the completion of treatment to 9 months
    • occurrence of infection (number of infections)
  • occurrence of infection (number of infections)
    • Time Frame: from the completion of treatment to 12 months
    • occurrence of infection (number of infections)
  • occurrence of infection (number of infections)
    • Time Frame: from the completion of treatment to 15 months
    • occurrence of infection (number of infections)
  • occurrence of infection (number of infections)
    • Time Frame: from the completion of treatment to 18 months
    • occurrence of infection (number of infections)
  • occurrence of infection (number of infections)
    • Time Frame: from the completion of treatment to 21 months
    • occurrence of infection (number of infections)
  • occurrence of infection (number of infections)
    • Time Frame: from the completion of treatment to 24 months
    • occurrence of infection (number of infections)
  • occurrence of infection (number of infections)
    • Time Frame: from the completion of treatment to 27 months
    • occurrence of infection (number of infections)
  • occurrence of infection (number of infections)
    • Time Frame: from the completion of treatment to 30 months
    • occurrence of infection (number of infections)
  • occurrence of infection (number of infections)
    • Time Frame: from the completion of treatment to 33 months
    • occurrence of infection (number of infections)
  • occurrence of infection (number of infections)
    • Time Frame: from the completion of treatment to 36 months
    • occurrence of infection (number of infections)
  • Concentration of blood immunoglobulin
    • Time Frame: from the completion of treatment to 3 months
    • Concentration of blood immunoglobulin
  • Concentration of blood immunoglobulin
    • Time Frame: from the completion of treatment to 6 months
    • Concentration of blood immunoglobulin
  • Concentration of blood immunoglobulin
    • Time Frame: from the completion of treatment to 9 months
    • Concentration of blood immunoglobulin
  • Concentration of blood immunoglobulin
    • Time Frame: from the completion of treatment to 12 months
    • Concentration of blood immunoglobulin
  • Concentration of blood immunoglobulin
    • Time Frame: from the completion of treatment to 15 months
    • Concentration of blood immunoglobulin
  • Concentration of blood immunoglobulin
    • Time Frame: from the completion of treatment to 18 months
    • Concentration of blood immunoglobulin
  • Concentration of blood immunoglobulin
    • Time Frame: from the completion of treatment to 21 months
    • Concentration of blood immunoglobulin
  • Concentration of blood immunoglobulin
    • Time Frame: from the completion of treatment to 24 months
    • Concentration of blood immunoglobulin
  • Concentration of blood immunoglobulin
    • Time Frame: from the completion of treatment to 27 months
    • Concentration of blood immunoglobulin
  • Concentration of blood immunoglobulin
    • Time Frame: from the completion of treatment to 30 months
    • Concentration of blood immunoglobulin
  • Concentration of blood immunoglobulin
    • Time Frame: from the completion of treatment to 33 months
    • Concentration of blood immunoglobulin
  • Concentration of blood immunoglobulin
    • Time Frame: from the completion of treatment to 36 months
    • Concentration of blood immunoglobulin
  • Concentration of T lymphocyte subsets
    • Time Frame: from the completion of treatment to 3 months
    • Concentration of T lymphocyte subsets
  • Concentration of T lymphocyte subsets
    • Time Frame: from the completion of treatment to 6 months
    • Concentration of T lymphocyte subsets
  • Concentration of T lymphocyte subsets
    • Time Frame: from the completion of treatment to 9 months
    • Concentration of T lymphocyte subsets
  • Concentration of T lymphocyte subsets
    • Time Frame: from the completion of treatment to 12 months
    • Concentration of T lymphocyte subsets
  • Concentration of T lymphocyte subsets
    • Time Frame: from the completion of treatment to 15 months
    • Concentration of T lymphocyte subsets
  • Concentration of T lymphocyte subsets
    • Time Frame: from the completion of treatment to 18 months
    • Concentration of T lymphocyte subsets
  • Concentration of T lymphocyte subsets
    • Time Frame: from the completion of treatment to 21 months
    • Concentration of T lymphocyte subsets
  • Concentration of T lymphocyte subsets
    • Time Frame: from the completion of treatment to 24 months
    • Concentration of T lymphocyte subsets
  • Concentration of T lymphocyte subsets
    • Time Frame: from the completion of treatment to 27 months
    • Concentration of T lymphocyte subsets
  • Concentration of T lymphocyte subsets
    • Time Frame: from the completion of treatment to 30 months
    • Concentration of T lymphocyte subsets
  • Concentration of T lymphocyte subsets
    • Time Frame: from the completion of treatment to 33 months
    • Concentration of T lymphocyte subsets
  • Concentration of T lymphocyte subsets
    • Time Frame: from the completion of treatment to 36 months
    • Concentration of T lymphocyte subsets
  • Concentraion of interleukin-2
    • Time Frame: from the completion of treatment to 3 months
    • Cytokines (concentraion of interleukin-2)
  • Concentraion of interleukin-2
    • Time Frame: from the completion of treatment to 6 months
    • Cytokines (concentraion of interleukin-2)
  • Concentraion of interleukin-2
    • Time Frame: from the completion of treatment to 9 months
    • Cytokines (concentraion of interleukin-2)
  • Concentraion of interleukin-2
    • Time Frame: from the completion of treatment to 12 months
    • Cytokines (concentraion of interleukin-2)
  • Concentraion of interleukin-2
    • Time Frame: from the completion of treatment to 15 months
    • Cytokines (concentraion of interleukin-2)
  • Concentraion of interleukin-2
    • Time Frame: from the completion of treatment to 18 months
    • Cytokines (concentraion of interleukin-2)
  • Concentraion of interleukin-2
    • Time Frame: from the completion of treatment to 21 months
    • Cytokines (concentraion of interleukin-2)
  • Concentraion of interleukin-2
    • Time Frame: from the completion of treatment to 24 months
    • Cytokines (concentraion of interleukin-2)
  • Concentraion of interleukin-2
    • Time Frame: from the completion of treatment to 27 months
    • Cytokines (concentraion of interleukin-2)
  • Concentraion of interleukin-2
    • Time Frame: from the completion of treatment to 30 months
    • Cytokines (concentraion of interleukin-2)
  • Concentraion of interleukin-2
    • Time Frame: from the completion of treatment to 33 months
    • Cytokines (concentraion of interleukin-2)
  • Concentraion of interleukin-2
    • Time Frame: from the completion of treatment to 36 months
    • Cytokines (concentraion of interleukin-2)
  • Body height
    • Time Frame: from the completion of treatment to 3 months
    • Body height
  • Body height
    • Time Frame: from the completion of treatment to 6 months
    • Body height
  • Body height
    • Time Frame: from the completion of treatment to 9 months
    • Body height
  • Body height
    • Time Frame: from the completion of treatment to 12 months
    • Body height
  • Body height
    • Time Frame: from the completion of treatment to 15 months
    • Body height
  • Body height
    • Time Frame: from the completion of treatment to 18 months
    • Body height
  • Body height
    • Time Frame: from the completion of treatment to 21 months
    • Body height
  • Body height
    • Time Frame: from the completion of treatment to 24 months
    • Body height
  • Body height
    • Time Frame: from the completion of treatment to 27 months
    • Body height
  • Body height
    • Time Frame: from the completion of treatment to 30 months
    • Body height
  • Body height
    • Time Frame: from the completion of treatment to 33 months
    • Body height
  • Body height
    • Time Frame: from the completion of treatment to 36 months
    • Body height
  • Body weight
    • Time Frame: from the completion of treatment to 3 months
    • Body weight
  • Body weight
    • Time Frame: from the completion of treatment to 6 months
    • Body weight
  • Body weight
    • Time Frame: from the completion of treatment to 9 months
    • Body weight
  • Body weight
    • Time Frame: from the completion of treatment to 12 months
    • Body weight
  • Body weight
    • Time Frame: from the completion of treatment to 15 months
    • Body weight
  • Body weight
    • Time Frame: from the completion of treatment to 18 months
    • Body weight
  • Body weight
    • Time Frame: from the completion of treatment to 21 months
    • Body weight
  • Body weight
    • Time Frame: from the completion of treatment to 24 months
    • Body weight
  • Body weight
    • Time Frame: from the completion of treatment to 27 months
    • Body weight
  • Body weight
    • Time Frame: from the completion of treatment to 30 months
    • Body weight
  • Body weight
    • Time Frame: from the completion of treatment to 33 months
    • Body weight
  • Body weight
    • Time Frame: from the completion of treatment to 36 months
    • Body weight
  • Tanner stage
    • Time Frame: from the completion of treatment to 3 months
    • Puberty change (Tanner stage)
  • Tanner stage
    • Time Frame: from the completion of treatment to 6 months
    • Puberty change (Tanner stage)
  • Tanner stage
    • Time Frame: from the completion of treatment to 9 months
    • Puberty change (Tanner stage)
  • Tanner stage
    • Time Frame: from the completion of treatment to 12 months
    • Puberty change (Tanner stage)
  • Tanner stage
    • Time Frame: from the completion of treatment to 15 months
    • Puberty change (Tanner stage)
  • Tanner stage
    • Time Frame: from the completion of treatment to 18 months
    • Puberty change (Tanner stage)
  • Tanner stage
    • Time Frame: from the completion of treatment to 21 months
    • Puberty change (Tanner stage)
  • Tanner stage
    • Time Frame: from the completion of treatment to 24 months
    • Puberty change (Tanner stage)
  • Tanner stage
    • Time Frame: from the completion of treatment to 27 months
    • Puberty change (Tanner stage)
  • Tanner stage
    • Time Frame: from the completion of treatment to 30 months
    • Puberty change (Tanner stage)
  • Tanner stage
    • Time Frame: from the completion of treatment to 33 months
    • Puberty change (Tanner stage)
  • Tanner stage
    • Time Frame: from the completion of treatment to 36 months
    • Puberty change (Tanner stage)
  • Occurrence of graft versus host disease
    • Time Frame: from the completion of treatment to 3 months
    • Occurrence of graft versus host disease
  • Occurrence of graft versus host disease
    • Time Frame: from the completion of treatment to 6 months
    • Occurrence of graft versus host disease
  • Occurrence of graft versus host disease
    • Time Frame: from the completion of treatment to 9 months
    • Occurrence of graft versus host disease
  • Occurrence of graft versus host disease
    • Time Frame: from the completion of treatment to 12 months
    • Occurrence of graft versus host disease
  • Occurrence of graft versus host disease
    • Time Frame: from the completion of treatment to 15 months
    • Occurrence of graft versus host disease
  • Occurrence of graft versus host disease
    • Time Frame: from the completion of treatment to 18 months
    • Occurrence of graft versus host disease
  • Occurrence of graft versus host disease
    • Time Frame: from the completion of treatment to 21 months
    • Occurrence of graft versus host disease
  • Occurrence of graft versus host disease
    • Time Frame: from the completion of treatment to 24 months
    • Occurrence of graft versus host disease
  • Occurrence of graft versus host disease
    • Time Frame: from the completion of treatment to 27 months
    • Occurrence of graft versus host disease
  • Occurrence of graft versus host disease
    • Time Frame: from the completion of treatment to 30 months
    • Occurrence of graft versus host disease
  • Occurrence of graft versus host disease
    • Time Frame: from the completion of treatment to 33 months
    • Occurrence of graft versus host disease
  • Occurrence of graft versus host disease
    • Time Frame: from the completion of treatment to 36 months
    • Occurrence of graft versus host disease

Participating in This Clinical Trial

Inclusion Criteria

1.Type 1 diabetes mellitus children with genetic immunodeficiency 1. Meet the diagnostic criteria of type 1 diabetes mellitus: clinical manifestations of typical diabetes mellitus include polyphagia, polyuria, weight loss, or diabetic ketoacidosis, confirmed by blood sugar level, islet function and autoimmune antibody. 2. Existence of extrapancreatic organ damage: (1) inflammatory bowel disease, (2) impairment of renal function, (3) repeated infection of mouth, skin, anus or whole body, (4) immune hepatitis, (5) persistent chronic immune iridocyclitis, (6) immune adrenalinitis leading to adrenocortical dysfunction, (7) pituitary inflammation leading to hypophysis, (8) rheumatoid disease, (9) immune vasculitis, (10) systemic lupus erythematosus, (11) other organs besides thyroid function damage. Suffering from one or more of above diseases. Recurrence after receiving regular clinical treatment, including symptomatic treatment of organ protective drugs. 3. Gene mutation was found according to gene diagnosis: gene mutation was found by gene sequencing. Literature searches at home and abroad confirmed that the defect of the gene resulted in autoimmune or immune dysfunction, resulting in multiple organ dysfunction and poor prognosis. Exclusion Criteria:

1. Mature and effective treatment methods are available. 2. HIV, HBV and HCV were positive. 3. A the active period of infection. 4. At the active stage of malignant tumors. 5. Combination of other fatal diseases. 6. Existence of mental and psychological diseases.

Gender Eligibility: All

Minimum Age: N/A

Maximum Age: 18 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Children’s Hospital of Fudan University
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Luo Feihong, Study Chair, Children’s Hospital of Fudan University
  • Overall Contact(s)
    • Luo Feihong, +862164931226, luofh@fudan.edu.cn

References

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Amin R, Widmer B, Prevost AT, Schwarze P, Cooper J, Edge J, Marcovecchio L, Neil A, Dalton RN, Dunger DB. Risk of microalbuminuria and progression to macroalbuminuria in a cohort with childhood onset type 1 diabetes: prospective observational study. BMJ. 2008 Mar 29;336(7646):697-701. doi: 10.1136/bmj.39478.378241.BE. Epub 2008 Mar 18.

Mollsten A, Svensson M, Waernbaum I, Berhan Y, Schon S, Nystrom L, Arnqvist HJ, Dahlquist G; Swedish Childhood Diabetes Study Group; Diabetes Incidence Study in Sweden; Swedish Renal Registry. Cumulative risk, age at onset, and sex-specific differences for developing end-stage renal disease in young patients with type 1 diabetes: a nationwide population-based cohort study. Diabetes. 2010 Jul;59(7):1803-8. doi: 10.2337/db09-1744. Epub 2010 Apr 27.

American Diabetes Association. (2) Classification and diagnosis of diabetes. Diabetes Care. 2015 Jan;38 Suppl:S8-S16. doi: 10.2337/dc15-S005. No abstract available.

Wildin RS, Smyk-Pearson S, Filipovich AH. Clinical and molecular features of the immunodysregulation, polyendocrinopathy, enteropathy, X linked (IPEX) syndrome. J Med Genet. 2002 Aug;39(8):537-45. doi: 10.1136/jmg.39.8.537.

Uzel G, Sampaio EP, Lawrence MG, Hsu AP, Hackett M, Dorsey MJ, Noel RJ, Verbsky JW, Freeman AF, Janssen E, Bonilla FA, Pechacek J, Chandrasekaran P, Browne SK, Agharahimi A, Gharib AM, Mannurita SC, Yim JJ, Gambineri E, Torgerson T, Tran DQ, Milner JD, Holland SM. Dominant gain-of-function STAT1 mutations in FOXP3 wild-type immune dysregulation-polyendocrinopathy-enteropathy-X-linked-like syndrome. J Allergy Clin Immunol. 2013 Jun;131(6):1611-23. doi: 10.1016/j.jaci.2012.11.054. Epub 2013 Mar 25.

Bennett CL, Christie J, Ramsdell F, Brunkow ME, Ferguson PJ, Whitesell L, Kelly TE, Saulsbury FT, Chance PF, Ochs HD. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat Genet. 2001 Jan;27(1):20-1. doi: 10.1038/83713.

Rao A, Kamani N, Filipovich A, Lee SM, Davies SM, Dalal J, Shenoy S. Successful bone marrow transplantation for IPEX syndrome after reduced-intensity conditioning. Blood. 2007 Jan 1;109(1):383-5. doi: 10.1182/blood-2006-05-025072. Epub 2006 Sep 21.

van de Veerdonk FL, Plantinga TS, Hoischen A, Smeekens SP, Joosten LA, Gilissen C, Arts P, Rosentul DC, Carmichael AJ, Smits-van der Graaf CA, Kullberg BJ, van der Meer JW, Lilic D, Veltman JA, Netea MG. STAT1 mutations in autosomal dominant chronic mucocutaneous candidiasis. N Engl J Med. 2011 Jul 7;365(1):54-61. doi: 10.1056/NEJMoa1100102. Epub 2011 Jun 29.

Toubiana J, Okada S, Hiller J, Oleastro M, Lagos Gomez M, Aldave Becerra JC, Ouachee-Chardin M, Fouyssac F, Girisha KM, Etzioni A, Van Montfrans J, Camcioglu Y, Kerns LA, Belohradsky B, Blanche S, Bousfiha A, Rodriguez-Gallego C, Meyts I, Kisand K, Reichenbach J, Renner ED, Rosenzweig S, Grimbacher B, van de Veerdonk FL, Traidl-Hoffmann C, Picard C, Marodi L, Morio T, Kobayashi M, Lilic D, Milner JD, Holland S, Casanova JL, Puel A; International STAT1 Gain-of-Function Study Group. Heterozygous STAT1 gain-of-function mutations underlie an unexpectedly broad clinical phenotype. Blood. 2016 Jun 23;127(25):3154-64. doi: 10.1182/blood-2015-11-679902. Epub 2016 Apr 25.

Leiding JW, Okada S, Hagin D, Abinun M, Shcherbina A, Balashov DN, Kim VHD, Ovadia A, Guthery SL, Pulsipher M, Lilic D, Devlin LA, Christie S, Depner M, Fuchs S, van Royen-Kerkhof A, Lindemans C, Petrovic A, Sullivan KE, Bunin N, Kilic SS, Arpaci F, Calle-Martin O, Martinez-Martinez L, Aldave JC, Kobayashi M, Ohkawa T, Imai K, Iguchi A, Roifman CM, Gennery AR, Slatter M, Ochs HD, Morio T, Torgerson TR; Inborn Errors Working Party of the European Society for Blood and Marrow Transplantation and the Primary Immune Deficiency Treatment Consortium. Hematopoietic stem cell transplantation in patients with gain-of-function signal transducer and activator of transcription 1 mutations. J Allergy Clin Immunol. 2018 Feb;141(2):704-717.e5. doi: 10.1016/j.jaci.2017.03.049. Epub 2017 Jun 7.

Niclauss N, Morel P, Berney T. Has the gap between pancreas and islet transplantation closed? Transplantation. 2014 Sep 27;98(6):593-9. doi: 10.1097/TP.0000000000000288.

Ahearn AJ, Parekh JR, Posselt AM. Islet transplantation for Type 1 diabetes: where are we now? Expert Rev Clin Immunol. 2015 Jan;11(1):59-68. doi: 10.1586/1744666X.2015.978291. Epub 2014 Dec 2.

Kopan C, Tucker T, Alexander M, Mohammadi MR, Pone EJ, Lakey JRT. Approaches in Immunotherapy, Regenerative Medicine, and Bioengineering for Type 1 Diabetes. Front Immunol. 2018 Jun 12;9:1354. doi: 10.3389/fimmu.2018.01354. eCollection 2018.

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