A Spectrum of Clinical Findings from ALPS to CVID: Several Novel LRBA Defects

Abstract

Objective:To analyze the development of psychopathology in recipients along with their donor and nondonor siblings and the relationship with the bone marrow transplantation (BMT) process.Methods: All children were interviewed using the Kiddie Schedule for Affective Disorders and Schizophrenia to assess psychopathology. The depression and anxiety symptoms and self-esteem of children and adolescents were evaluated using the Children's Depression Inventory, State-Trait Anxiety Inventory for Children, State-Trait Anxiety Inventory, and Rosenberg Self-Esteem Scale.Results: In this study, the depressive symptom level was found significantly higher in the donor group compared with the nondonor group. State anxiety symptoms were higher in the BMT group (P < .05). There were no significant differences in trait anxiety symptoms. Self-respect was higher in children in the donor group compared with those in the BMT group (P < .05). During the transplant process, children with bone marrow transplants had a higher prevalence of depression, anxiety disorder, and attention-deficit/hyperactivity disorder, and nondonor siblings had a higher prevalence of depressive disorder, anxiety disorder, and attention-deficit/hyperactivity disorder compared with society in general. Conclusion:Physicians should deal with the family as a whole, not just their patient, and should be aware of the psychiatric risk of other siblings during the assessment.

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

“…We observed that only 1 of 10 patients who received a transplant had died after the transplantation procedures that were performed after 2015; in addition, 7 patients with LRBA deficiency of a Turkish cohort who received a transplant were recently reported (but not included in the present study) to be well and still living, with a median follow-up of 2 years after their transplantation procedure. 3 These findings suggest that the conclusions from early reports suggesting that LRBA deficiency per se was associated with a high TRM should be revised. In the current study, the transplantation outcome was clearly better in patients with lower IDDA scores (100% survival in patients with an IDDA score of <15) and thus better pre-HSCT clinical conditions.…”

“…Background: Recent findings strongly support hematopoietic Abbreviations used CNS: Central nervous system CTLA4: Cytotoxic T-lymphocyte antigen 4 HSCT: Hematopoietic stem cell transplantation IDDA: Immune deficiency and dysregulation activity score IPEX: Immunodysregulation polyendocrinopathy enteropathy Xlinked LRBA: LPS-responsive beige-like anchor PR: Partial remission Treg: Regulatory T TRM: Transplant-related mortality WBC: White blood cell LPS-responsive beige-like anchor protein (LRBA) deficiency, first described in 2012, 1 is a severe primary immunodeficiency with a broad spectrum of clinical and immunologic manifestations caused by biallelic mutations in the LRBA gene. [2][3][4][5][6] LRBA is ubiquitously expressed and involved in signal transduction, vesicular trafficking, autophagy, and apoptosis; abolished expression may impair key processes related to immunity. 1,7,8 LRBA normally prevents cytotoxic T-lymphocyte protein-4 (CTLA4) from lysosomal degradation by bringing it back to the cell surface; its absence leads to decreased CTLA4 expression.…”

Bronchiectasis in common variable immunodeficiency: A systematic review and meta‐analysis

“…21,22 In addition, the patients with earlyonset CVID are more likely to have a monogenetic defect (such as, LRBA, CTLA-4, PIK3CD) that may lead to bronchiectasis to due severe immune dysregulations that are associated with an inflammatory response in the lung. [23][24][25][26] This may be different from the development of bronchiectasis in patients with adult-onset CVID, in which the etiology may be more chronic and patients may less often have inflammatory lung disease.…”

“…It was reported that patients with CVID and parental consanguinity that diagnosed in childhood are more severely affected by autoimmunity, inflammatory lung disease, and enteropathy than adults diagnosed later in life . In addition, the patients with early‐onset CVID are more likely to have a monogenetic defect (such as, LRBA, CTLA‐4, PIK3CD) that may lead to bronchiectasis to due severe immune dysregulations that are associated with an inflammatory response in the lung . This may be different from the development of bronchiectasis in patients with adult‐onset CVID, in which the etiology may be more chronic and patients may less often have inflammatory lung disease.…”

Heterogeneity of Liver Disease in Common Variable Immunodeficiency Disorders

“…LRBA plays a pivotal role in CTLA-4 surface expression, by rescuing endosomal CTLA-4 from lysosomal degradation. Clinical manifestations of LRBA deficiency include early-onset hypogammaglobulinemia, autoimmune manifestations, IBD and recurrent infections (107). The largest cohort study, describing clinical features of LRBA-deficiency in 22 subjects, reports hepatomegaly in 24% patients, with three subjects diagnosed with autoimmune hepatitis (108).…”