Abatacept is useful in autoimmune cytopenia with immunopathologic manifestations caused by CTLA-4 defects

Dhunputh, Chloé; Ducassou, Stéphane; Fernandes, Helder; Pïcard, Capucine; Rieux-Laucat, Frédéric; Viallard, Jean‐François; Lazaro, Estibaliz; Hermine, Olivier; Jouvray, Mathieu; Machelart, Irène; Lambilliotte, Anne; Malphettes, Marion; Moshous, Despina; Neven, Bénédicte; Gauthier, Alexandra; Garnier, Nathalie; Leblanc, Thierry; Landman‐Parker, Judith; Leverger, Guy; Aladjidi, Nathalie

doi:10.1182/blood.2021013496

Cited by 12 publications

(11 citation statements)

References 21 publications

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“…In the same year Schubert et al identified 14 patients from 6 families, of whom 11 had enteropathy and 10 hypogammaglobulinemia; other manifestations included granulomatous lymphocytic interstitial lung disease (ILD), respiratory infections, organ infiltration, cytopenias, lymphadenopathy, skin diseases, autoimmune thyroiditis, arthritis, and one case of solid cancer (47). The CTLA-4 fusion proteins Abatacept and Belatacept have shown promising results in ameliorating disease symptoms, but the very long-term outcome of their use is unknown (48,49).…”

Section: Emerging Ieimentioning

confidence: 99%

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Personalized hematopoietic stem cell transplantation for inborn errors of immunity

Slatter

Lum

2023

Front. Immunol.

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Patients with inborn errors of immunity (IEI) have been transplanted for more than 50 years. Many long-term survivors have ongoing medical issues showing the need for further improvements in how hematopoietic stem cell transplantation (HSCT) is performed if patients in the future are to have a normal quality of life. Precise genetic diagnosis enables early treatment before recurrent infection, autoimmunity and organ impairment occur. Newborn screening for severe combined immunodeficiency (SCID) is established in many countries. For newly described disorders the decision to transplant is not straight-forward. Specific biologic therapies are effective for some diseases and can be used as a bridge to HSCT to improve outcome. Developments in reduced toxicity conditioning and methods of T-cell depletion for mismatched donors have made transplant an option for all eligible patients. Further refinements in conditioning plus precise graft composition and additional cellular therapy are emerging as techniques to personalize the approach to HSCT for each patient

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Section: Emerging Ieimentioning

confidence: 99%

“…It also enhances T regulatory cells and has been shown to be effective. The CTLA-4 fusion proteins Abatacept and Belatacept show promising results in these disorders ( 48 , 49 ).…”

Section: Bridging Treatmentsmentioning

confidence: 99%

Personalized hematopoietic stem cell transplantation for inborn errors of immunity

Slatter

Lum

2023

Front. Immunol.

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“…A summary of current alternative choices for second line therapy that have been utilized for specific gene variants reported in patients with ES are listed in Table 2. The experience with abatacept as targeted therapy in CTLA4 defects has been highly successful and provides promise that this approach may be effective for other patients with other specific genetic variants 30 . There is no doubt that this list of alternatives will grow and become even more specific in the months and years ahead, so it is even more critical that global collaborative investigators work to identify the most effective treatment pathways in this very rare disorder.…”

Section: Treatment Optionsmentioning

confidence: 99%

“…The experience with abatacept as targeted therapy in CTLA4 defects has been highly successful and provides promise that this approach may be effective for other patients with other specific genetic variants. 30 There is no doubt that this list of alternatives will grow and become even more specific in the months and years ahead, so it is even more critical that global collaborative investigators work to identify the most effective treatment pathways in this very rare disorder. Hopefully, for those with monogenic pathogenic variants, gene therapy, gene editing, cellular therapies will offer curative options in the near future as well.…”

Section: Tr E Atm E N T Op Tionsmentioning

confidence: 99%

Paediatric‐onset Evans syndrome: Breaking away from refractory immune thrombocytopenia

Aladjidi,

Pincez,

Rieux‐Laucat

et al. 2023

Br J Haematol

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SummarySince its first description by Evans in 1951, this syndrome has been linked to chronic immune thrombocytopenia with the concurrent or delayed onset of autoimmune haemolytic anaemia or neutropenia. For decades, the evolution of Evans syndrome (ES) has carried a poor prognosis and often resulted in chronic steroid exposure, multiple immune suppressing medications directed against T or B lymphocytes, and splenectomy. This paper presents a new view of ES based on recent advances in genomics which begin to classify patients based on their underlying molecular variants in previously described primary immune disorders. This has opened up new avenues of targeted therapy or bone marrow transplant at rather than broad long‐term immune suppression or splenectomy. Importantly, recent studies of the full lifespan of ES suggest that at least 80% of those paediatric patients will progress to various clinical or biological immunopathological manifestations with age despite the resolution of their cytopenias. Those patients merit long‐term follow‐up and monitoring in dedicated transition programs to improve outcome at the adult age.

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“…Along with symptomatic therapies (anti-infective and anti-inflammatory treatment, first-line immunosuppressive treatment against autoimmune cytopenias and inflammatory parenchymal lung disease), many patients benefit from rapamycin (mTOR) inhibitors, and soluble CTLA-4-Ig (Abatacept, Belatacept), functioning in vivo as inhibitors of T-cell activation, mimicking CTLA4 function ( 68 ). In particular, the efficacy of Abatacept in auto-immune cytopenias caused by CTLA-4 haploinsufficiency has been well characterized ( 69 ). It is important to underline that the possibility of viral infection/reactivation during the treatment with Abatacept or Belatacept may be a limitation for the use of these drugs.…”

Section: Targeted Therapy In Immune Dysregulation Disorders Of Aicsmentioning

confidence: 99%

Pathogenesis of Autoimmune Cytopenias in Inborn Errors of Immunity Revealing Novel Therapeutic Targets

et al. 2022

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Autoimmune diseases are usually associated with environmental triggers and genetic predisposition. However, a few number of autoimmune diseases has a monogenic cause, mostly in children. These diseases may be the expression, isolated or associated with other symptoms, of an underlying inborn error of immunity (IEI). Autoimmune cytopenias (AICs), including immune thrombocytopenic purpura (ITP), autoimmune hemolytic anemia (AIHA), autoimmune neutropenia (AN), and Evans’ syndrome (ES) are common presentations of immunological diseases in the pediatric age, with at least 65% of cases of ES genetically determined. Autoimmune cytopenias in IEI have often a more severe, chronic, and relapsing course. Treatment refractoriness also characterizes autoimmune cytopenia with a monogenic cause, such as IEI. The mechanisms underlying autoimmune cytopenias in IEI include cellular or humoral autoimmunity, immune dysregulation in cases of hemophagocytosis or lymphoproliferation with or without splenic sequestration, bone marrow failure, myelodysplasia, or secondary myelosuppression. Genetic characterization of autoimmune cytopenias is of fundamental importance as an early diagnosis improves the outcome and allows the setting up of a targeted therapy, such as CTLA-4 IgG fusion protein (Abatacept), small molecule inhibitors (JAK-inhibitors), or gene therapy. Currently, gene therapy represents one of the most attractive targeted therapeutic approaches to treat selected inborn errors of immunity. Even in the absence of specific targeted therapies, however, whole exome genetic testing (WES) for children with chronic multilineage cytopenias should be considered as an early diagnostic tool for disease diagnosis and genetic counseling.

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Abatacept is useful in autoimmune cytopenia with immunopathologic manifestations caused by CTLA-4 defects

Cited by 12 publications

References 21 publications

Personalized hematopoietic stem cell transplantation for inborn errors of immunity

Personalized hematopoietic stem cell transplantation for inborn errors of immunity

Paediatric‐onset Evans syndrome: Breaking away from refractory immune thrombocytopenia

Pathogenesis of Autoimmune Cytopenias in Inborn Errors of Immunity Revealing Novel Therapeutic Targets

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