Neurology(R) neuroimmunology & neuroinflammation · 2024
Abatacept Induces Long-Term Reconstitution of the B-Cell Niche in a Patient With CTLA-4 Haploinsufficiency: A Case Report.
СтатьяКлинический случайНазвание и аннотация: Перевод в очереди
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Pfeuffer Steffen, Nelke Christopher, Pawlitzki Marc, Ruck Tobias, Schroeter Christina B, Thomas Christian, Kobbe Guido, Dietrich Sascha, Zimprich Alexander A, Wiendl Heinz, Meuth Sven G
Аннотация
OBJECTIVES: Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) haploinsufficiency is a rare genetic condition characterized by development of immune cytopenia, hypogammaglobulinemia, and/or lymphoproliferative disorder, as well as multiple autoimmunity. Treatment with abatacept was shown to alleviate autoimmune conditions, yet its long-lasting impact on bone marrow function remains undetermined.
METHODS: We here present the case of a now 39-year-old woman with CTLA-4 haploinsufficiency with predominant CNS affection, yet multiorgan autoimmunity and lymphopenia. We conducted single-cell RNA sequencing (scRNA-seq) of peripheral mononuclear blood cells before and after abatacept induction.
RESULTS: After several high-efficacy immunosuppressive treatments with little-to-no response, she started abatacept in 2017 and experienced ongoing remission including resolution of pre-existing immune cytopenia and hypogammaglobulinemia. Using scRNA-seq, we were able to demonstrate reconstitution of peripheral B cells accompanied by reduction of CD8+ T cells. CD4+ and CD8+ T cells were characterized by downregulation of pathways involved in activation of innate immune cells.
DISCUSSION: Our findings demonstrate long-lasting resolution of lymphopenia after abatacept treatment in CTLA-4 haploinsufficiency despite severity and duration of symptoms. Thus, abatacept should be considered throughout before stem cell transplantation also in CTLA-4 haploinsufficiency with severe symptoms.
CLASSIFICATION OF EVIDENCE: As a single report without controls, this report provides class IV evidence that abatacept might revert lymphopenia in patients with CTLA-4 haploinsufficiency.
METHODS: We here present the case of a now 39-year-old woman with CTLA-4 haploinsufficiency with predominant CNS affection, yet multiorgan autoimmunity and lymphopenia. We conducted single-cell RNA sequencing (scRNA-seq) of peripheral mononuclear blood cells before and after abatacept induction.
RESULTS: After several high-efficacy immunosuppressive treatments with little-to-no response, she started abatacept in 2017 and experienced ongoing remission including resolution of pre-existing immune cytopenia and hypogammaglobulinemia. Using scRNA-seq, we were able to demonstrate reconstitution of peripheral B cells accompanied by reduction of CD8+ T cells. CD4+ and CD8+ T cells were characterized by downregulation of pathways involved in activation of innate immune cells.
DISCUSSION: Our findings demonstrate long-lasting resolution of lymphopenia after abatacept treatment in CTLA-4 haploinsufficiency despite severity and duration of symptoms. Thus, abatacept should be considered throughout before stem cell transplantation also in CTLA-4 haploinsufficiency with severe symptoms.
CLASSIFICATION OF EVIDENCE: As a single report without controls, this report provides class IV evidence that abatacept might revert lymphopenia in patients with CTLA-4 haploinsufficiency.