A124 UNDERSTANDING THE ROLE OF LRBA AND CHARACTERIZING THE PHENOTYPE OF LRBA-DEFICIENCY IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE
Bibliographic record
Abstract
The prevalence of inflammatory bowel disease (IBD) in the Western hemisphere is increasing. IBD is a family of autoimmune diseases causing inflammation in the gastrointestinal tract which typically presents in two major forms: Crohn’s disease or ulcerative colitis. The pathogenesis of these diseases is driven by several factors including environmental stress, dysbiosis of the gut microbiota, and genetic susceptibility. Recent research has identified a growing number of IBD-risk loci in various genes, including a novel interesting IBD-related gene is Lipopolysaccharide Responsive Beige-Like Anchor (LRBA). LRBA-deficiency results in immunodeficiency, autoimmunity, defective B cell differentiation, and hypogammaglobulinemia. In our own pediatric patient cohort, we have identified a patient with a rare damaging variant in LRBA (chr4: CC/AA; E1916X, exon 36) through whole-exome sequencing. Little is known about the function of LRBA but there seems to be a consensus that LRBA may be a scaffold or adaptor protein and has a role in endosomal trafficking. To study the significance of this mutation on the functional role of LRBA and its potential effect on deregulating autophagy is being investigated. BioID biotinylation tagging experiments were performed on HEK293T cells overexpressing FLAG-LC3B, which identified LRBA as one of the highest fidelity hits among the many autophagic proteins. This interaction will be confirmed by performing co-immunoprecipitation. To characterize the phenotype of LRBA-deficiency, apoptosis assays on HAP1 LRBA-KO cell line will be performed. In addition, immunofluorescence and staining for autophagy markers, such as LC3B and p62 will be performed to determine if LRBA-deficient cells have an autophagy defect. The BioID results indicated that LC3B may be in close proximity to LRBA. We suspect that LRBA co-localizes with LC3B and that they may interact in a larger complex during the fusion of the endosome and autophagosome. Furthermore, the phenotype in the HAP1 LRBA-KO cell line shows a morphological difference compared to the HAP1 wildtype cell line. More studies will be performed to confirm an apoptotic and/or autophagy defect in LRBA-deficient cells. Our data suggest that a loss of LRBA expression may lead to defects in autophagy, which in turn may contribute to the IBD phenotype observed in LRBA-deficient patients. CIHRThe Leona M. and Harry B. Helmsley Charitable Trust
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".