Observational Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Jul 26, 2021; 9(21): 5873-5888
Published online Jul 26, 2021. doi: 10.12998/wjcc.v9.i21.5873
Potential protein–phenotype correlation in three lipopolysaccharide-responsive beige-like anchor protein-deficient patients
Wen-Juan Tang, Wen-Hui Hu, Ying Huang, Bing-Bing Wu, Xiao-Min Peng, Xiao-Wen Zhai, Xiao-Wen Qian, Zi-Qing Ye, Hai-Jiao Xia, Jie Wu, Jie-Ru Shi
Wen-Juan Tang, Wen-Hui Hu, Ying Huang, Zi-Qing Ye, Hai-Jiao Xia, Jie Wu, Jie-Ru Shi, Department of Gastroenterology, Pediatric Inflammatory Bowel Disease Research Center, Children’s Hospital of Fudan University, National Children's Medical Center, Shanghai 201102, China
Bing-Bing Wu, Xiao-Min Peng, The Molecular Genetic Diagnosis Center, Children's Hospital of Fudan University, Shanghai 201102, China
Xiao-Wen Zhai, Xiao-Wen Qian, Department of Hematology Oncology, Children's Hospital of Fudan university, National Children's Medical Center, Shanghai 201102, China
Author contributions: Tang WJ and Hu WH contributed equally to this manuscript; Huang Y, Zhai XW, and Qian XW designed the research study; Tang WJ and Hu WH performed the research and contributed to analysis of the data; Tang WJ wrote the manuscript; Wu BB and Peng XM contributed analytic tools; Ye ZQ, Xia HJ, Shi JR, and Wu J contributed to acquisition of the data; all authors have read and approved the final manuscript.
Institutional review board statement: The study was reviewed and approved by the research ethics committee at the Children's Hospital of Fudan University (2015-130).
Informed consent statement: Informed consent for participation were obtained from the parents.
Conflict-of-interest statement: There are no conflicts of interest to report.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement, and the manuscript was prepared and revised according to the STROBE Statement.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ying Huang, MD, PhD, Chief Doctor, Professor, Department of Gastroenterology, Pediatric Inflammatory Bowel Disease Research Center, Children’s Hospital of Fudan University, National Children's Medical Center, No. 399 Wanyuan Road, Shanghai 201102, China. yhuang2019@126.com
Received: February 3, 2021
Peer-review started: February 3, 2021
First decision: March 14, 2021
Revised: March 22, 2021
Accepted: May 26, 2021
Article in press: May 26, 2021
Published online: July 26, 2021
Processing time: 167 Days and 23.4 Hours
Abstract
BACKGROUND

Patients with lipopolysaccharide (LPS)-responsive beige-like anchor protein (LRBA) deficiency have a variety of clinical symptoms, but there is no apparent genotype–phenotype correlation, and patients carrying the same mutations may have different phenotypes. Therefore, it is not easy for doctors to make a decision regarding hematopoietic stem cell transplantation (HSCT) for LRBA-deficient patients. We hypothesized that there may be a protein–phenotype correlation to indicate HSCT for LRBA-deficient patients.

AIM

To report on three Chinese LRBA-deficient patients and determine the correlation between residual protein expression and disease phenotypes.

METHODS

Clinical data of three Chinese LRBA-deficient patients were collected, and protein levels were detected by Western blot analysis. In addition, LRBA mutation information of another 83 previously reported patients was summarized.

RESULTS

All the major clinical findings indicated enteropathy, but patients 1 and 3 presented with more severe symptoms than patient 2. Endoscopy and histology indicated nonspecific colitis for patients 1 and 3 but Crohn's disease-like colitis for patient 2. Compound heterozygous mutations in LRBA were found in patient 1, and homozygous mutations in LRBA were found in patient 2 and patient 3. Only patient 2 responded well to traditional immunosuppressive treatment. Residual expression of the LRBA protein in patients 1 and 3 was very low, but in patient 2, a more than 0.5-fold in expression of the LRBA protein was found compared to that in the control. After HSCT, patient 1 had increased LRBA protein expression. We summarized the genetic information of 86 patients, and the mutations in patients 1 and 3 were novel mutations.

CONCLUSION

We described three Chinese LRBA-deficient patients, two of whom carried novel mutations. These patients had no genotype-phenotype correlations, but their residual LRBA protein expression might be associated with disease outcome and could be an indicator for HSCT.

Keywords: LPS-responsive beige-like anchor protein deficiency; Chinese; Common variable immunodeficiency; Gene mutation; Chronic diarrhea

Core Tip: Previous studies have showed that there is no apparent genotype–phenotype correlation for lipopolysaccharide-responsive beige-like anchor protein (LRBA) deficiency, but a protein–phenotype correlation may exist. In this study, we described three Chinese patients with LRBA deficiency. Although all their major clinical findings indicated enteropathy, they had different endoscopy findings and different response to the immunosuppressive treatment. Functional experiments revealed that a lack of LRBA protein expression may lead to worse disease outcomes and be an indicator for hematopoietic stem cell transplantation (HSCT). The results of this study will be valuable for the selection of an immunosuppressive treatment or HSCT for treating LRBA-deficient patients in the future.