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Published January 1, 2023 | Version v1
Journal article Open

Therapeutic modalities and clinical outcomes in a large cohort with LRBA deficiency and CTLA4 insufficiency

Creators

  • 1. Marmara Univ, Sch Med, Dept Pediat, Istanbul, Turkiye
  • 2. TUBITAK Marmara Res Ctr, Gene Engn & Biotechnol Inst, Gebze, Turkiye
  • 3. Marmara Univ, Sch Med, Istanbul, Turkiye
  • 4. Ankara Univ, Fac Med, Div Pediat Allergy & Immunol, Ankara, Turkiye
  • 5. Univ Hlth Sci, Dr Behcet Uz Childrens Educ & Res Hosp, Div Pediat Allergy & Immunol, Izmir, Turkiye
  • 6. Ege Univ, Fac Med, Div Allergy & Immunol, Izmir, Turkiye
  • 7. Marmara Univ Training & Res Hosp, Div Allergy & Immunol, Minist Hlth, Istanbul, Turkiye
  • 8. Cukurova Univ, Div Pediat Allergy & Immunol, Fac Med, Adana, Turkiye
  • 9. Ondokuz Mayis Univ, Div Pediat Allergy & Immunol, Fac Med, Samsun, Turkiye
  • 10. Gaziantep Univ, Div Pediat Allergy & Immunol, Fac Med, Gaziantep, Turkiye
  • 11. Uludag Univ, Div Pediat Immunol & Rheumatol, Fac Med, Bursa, Turkiye
  • 12. Mersin Univ, Div Pediat Allergy & Immunol, Fac Med, Mersin, Turkiye
  • 13. Minist Hlth, Dept Allergy & Immunol, Batman Training & Res Hosp, Batman, Turkiye
  • 14. Univ Hlth Sci, Manisa City Hosp, Pediat Allergy & Immunol, Manisa, Turkiye

Description

Background: LPS-responsive beige-like anchor (LRBA) deficiency (LRBA-/-) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA4) insufficiency (CTLA41/-) are mechanistically overlapped diseases presenting with recurrent infections and autoimmunity. The effectiveness of different treatment regimens remains unknown. Objective: Our aim was to determine the comparative efficacy and long-term outcome of therapy with immunosuppressants, CTLA4-immunoglobulin (abatacept), and hematopoietic stem cell transplantation (HSCT) in a single-country multicenter cohort of 98 patients with a 5-year median follow-up.Methods: The 98 patients (63 LRBA-/- and 35 CTLA41/-) were followed and evaluated at baseline and every 6 months for clinical manifestations and response to the respective therapies.Results: The LRBA-/- patients exhibited a more severe disease course than did the CTLA41/- patients, requiring more immunosuppressants, abatacept, and HSCT to control their symptoms. Among the 58 patients who received abatacept as either a primary or rescue therapy, sustained complete control was achieved in 46 (79.3%) without severe side effects. In contrast, most patients who received immunosuppressants as primary therapy (n = 61) showed either partial or no disease control (72.1%), necessitating additional immunosuppressants, abatacept, or transplantation. Patients with partial or no response to abatacept (n = 12) had longer disease activity before abatacept therapy, with higher organ involvement and poorer disease outcomes than those with a complete response. HSCT was performed in 14 LRBA-/- patients; 9 patients (64.2%)showed complete remission , 3 (21.3%) continued to receive immunosuppressants after transplantation. HSCT , abatacept therapy gave rise to similar probabilities of survival. Conclusions: Abatacept is superior to immunosuppressants in controlling disease manifestations over the long term, especially when started early, and it may provide a safe and effective therapeutic alternative to transplantation. (J Allergy Clin Immunol 2023;152:1634-45.)

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