Long-term outcome of LRBA deficiency in 76 patients after various treatment modalities as evaluated by the immune deficiency and dysregulation activity (IDDA) score

Abstract

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 5 .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.

Interstitial Lung Disease in Children With Selected Primary Immunodeficiency Disorders—A Multicenter Observational Study

“…As reported by other authors, similar effects may be obtained with the CTLA-4 fusion protein abatacept. The effectiveness of this treatment has been documented, particularly in patients with LRBA deficiency (53)(54)(55). Our patient with LRBA deficiency was treated with GCs as a first-line therapy, and mycophenolate mofetil and rapamycin as a second-line therapy, but did not receive abatacept treatment.…”

“…However, HSCT was reported to be applied to some patients with malignancies, refractory autoimmune cytopenias, ILD/GLILD, and/or autoimmune enteropathy, among others in patients with LRBA deficiency (58). As reported by Tesch et al, HSCT in these patients was associated with an increased risk of death in the course of early post-transplant complications, but HSCT survivors achieved remission of disease symptoms (including ILD), in contrast to patients who had not undergone transplantation (55). The overall survival rate of patients undergoing HSCT was 70.8%, and the vast majority (70.6%) didn't require further immunosuppressive treatment (55).…”

Monogenic Inflammatory Bowel Disease: It's Never Too Late to Make a Diagnosis

“…Hematopoietic stem cell transplantation (HSCT) is suggested as a curative treatment for LRBA-deficient patients suffering from severe and refractory clinical manifestations, with good outcomes in different studies (47,48). Interestingly, in some patients, residual autoimmune features persisted after HSCT (47), which may suggest that LRBA has a role in non-immune cells as well. The clinical manifestations of the reported patient were compared to 103 patients with LRBA deficiency reported elsewhere (37).…”

How to evaluate for immunodeficiency in patients with autoimmune cytopenias: laboratory evaluation for the diagnosis of inborn errors of immunity associated with immune dysregulation

“…Therefore, pharmacological/biological manipulation of the immune system would benefit from the study of the IEIs, which offers a window into the consequences of immune manipulation and could facilitate the rational design of newer therapeutic interventions. 61,62…”