Loss-of-function of lipopolysaccharide-responsive beige-like anchor protein causes inflammatory bowel disease—a case report and literature review
Case Report

Loss-of-function of lipopolysaccharide-responsive beige-like anchor protein causes inflammatory bowel disease—a case report and literature review

Zhixin Wang, Youhong Fang, Jindan Yu, Jie Chen, Youyou Luo ORCID logo

Department of Gastroenterology, the Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China

Contributions: (I) Conception and design: Y Luo; (II) Administrative support: J Chen; (III) Provision of study materials or patients: Y Fang, J Yu, Y Luo; (IV) Collection and assembly of data: Z Wang, Y Luo; (V) Data analysis and interpretation: Z Wang; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

Correspondence to: Youyou Luo, MD, PhD. Department of Gastroenterology, the Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, No. 3333, Binsheng Road, Binjiang District, Hangzhou 310000, China. Email: looloohi@zju.edu.cn.

Background: Most cases of childhood inflammatory bowel disease (IBD) are polygenic in origin, although a subset of patients exhibits monogenic etiologies. Some studies have identified the lipopolysaccharide-responsive beige-like anchor protein (LRBA) gene as a susceptibility gene, but the majority of research has focused on genetic mutations without extensive clinical data. Furthermore, there is a paucity of long-term data on pediatric patients receiving biologic therapy.

Case Description: An 11-year-old female patient presented to the Gastroenterology Department with a 1-month history of chronic abdominal pain, diarrhea, and weight loss. Laboratory investigations revealed marked inflammation, anemia, hypoproteinemia, and elevated counts of naive B-cell. Endoscopic examination identified ulcers and polyp proliferation, which was consistent with an initial diagnosis of Crohn’s disease. However, despite several months of standardized treatment, there was no significant clinical improvement. Subsequent genetic testing identified LRBA deficiency with a novel mutation. Following the adjustment of her biologic treatment regimen, the patient eventually achieved clinical remission. We also conducted a literature review on LRBA deficiency and IBD. The effective therapies mentioned were hematopoietic stem cell transplantation (HSCT) and abatacept.

Conclusions: We described a Chinese IBD and LRBA-deficient patient carrying a novel mutation. In this context, the patient achieved remission under regular biologic therapy, which may offer valuable insights for the treatment of similar cases.

Keywords: Lipopolysaccharide-responsive beige-like anchor protein deficiency (LRBA deficiency); inflammatory bowel disease (IBD); Crohn’s disease (CD); biologic therapy; case report

Submitted Dec 08, 2024. Accepted for publication May 06, 2025. Published online Jun 13, 2025.

doi: 10.21037/tp-2024-567

Highlight box

Key findings

• We described a Chinese inflammatory bowel disease (IBD) and lipopolysaccharide-responsive beige-like anchor protein (LRBA)-deficient patient, carrying a novel mutation, who achieved remission under regular biologic therapy.

What is known and what is new?

• Loss of LRBA function can lead to immune dysregulation, as well as a broad spectrum of clinical phenotypes, including chronic diarrhea, while a few of the patients were diagnosed with IBD. Among those several cases, the effective treatments were abatacept and hematopoietic stem cell transplantation (HSCT), long-term data of children on biologic therapy are scarce in the literature.

• We reported the clinical details of an LRBA patient with IBD who achieved remission under regular biologic therapy.

What is the implication, and what should change now?

• We should be aware of the possibility of LRBA deficiency for IBD patients showing unsatisfactory treatment efficacy, and biologic therapy may lead to clinical remission.

Introduction

Background

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract and includes ulcerative colitis, Crohn’s disease (CD), and indeterminate IBD. Although its etiopathogenesis is unclear, it is believed to be a complex interplay among genetic factors, the environment (including the intestinal microbiome), and the gut-immune system (1). As next-generation DNA sequencing (NGS) technology has advanced, several specific genes, including the lipopolysaccharide-responsive beige-like anchor protein (LRBA) gene, have been found to be linked to IBD, leading to the discovery of monogenic IBD (2). LRBA is a protein encoded by the LRBA gene that is involved in regulating immune cells, especially regulatory T (Treg) cells (3). Biallelic mutations in the LRBA gene cause a condition called LRBA deficiency. Loss of LRBA function can lead to immune dysregulation, as well as a broad spectrum of clinical phenotypes, including autoimmunity, splenomegaly, Evans syndrome, lymphoma, chronic diarrhea, hypogammaglobulinemia, and recurrent infections (4). Here, a patient with relapsed chronic diarrhea and abdominal pain after systematic treatment for her initial diagnosis of IBD, who was ultimately confirmed to be a LRBA-deficient was described, and we compared our findings with the available literature. We present this case in accordance with the CARE reporting checklist (available at https://tp.amegroups.com/article/view/10.21037/tp-2024-567/rc).

Case presentation

In February 2020, an 11-year-old female patient presented to our Department of Gastroenterology with complaints of chronic abdominal pain, diarrhea, and weight loss of 5 kg. The onset of symptoms occurred one month prior and was characterized by yellow, loose stools occurring 3–4 times daily, often containing mucus but devoid of blood. The patient also reported experiencing periumbilical or lower abdominal pain, which was exacerbated postprandially and alleviated following defecation. Additionally, the patient experienced nausea without episodes of vomiting or melena. Prior to this presentation, the patient had sought medical attention at various other hospitals since the onset of her symptoms, and she was initially diagnosed with gastroenteritis and received antibiotic therapy. However, the effects of this treatment are not satisfactory. After several days of intermittent fever, the patient underwent enhanced computed tomography (CT) examination, which revealed widespread thickening of the colonic wall, and was subsequently transferred to our hospital. The patient’s past history and birth and development history were unremarkable. There was no family history of these symptoms. The girl has a younger brother, aged 7 years, who is healthy. There was also no consanguinity between parents.

Physical examination revealed stable vital signs and poor nutritional status, and the body mass index (BMI)-for-age Z score was −2.28 standard deviation (SD). The abdomen was flat with muscle tension, and tenderness without rebound tenderness was felt in the lower abdomen and around the navel. In the examination of the perianal region, excrescence was observed at the 6 o’clock position in the lithotomic position, with tenderness. No other abnormal findings were identified.

Routine blood tests revealed C-reactive protein (CRP) elevation and a decrease in hemoglobin, which consistently fluctuated between 37.7 and 61.1 mg/L and between 93 and 112 g/L, respectively. Biochemical analysis of the liver and kidney revealed a normal range except for significantly decreased albumin (28.3 g/L) and prealbumin (75.7 mg/L) levels. Folic acid and vitamin D levels decreased during nutritional tests, whereas erythrocyte sedimentation rates increased. Fecal routine tests revealed occult blood 1+. Further immune-related investigations revealed slight increases in the levels of serum IgG and IgA and a marked increase in the level of serum IgE (1,190 IU/mL). For lymphocyte subset enumeration, cellular immune functions included reduced CD19 B cells and elevated CD4+ T cells.

The B-cell compartment contained a normal number of total B cells. In the analysis of different B-cell subsets, the naive B-cell count was 274.42/µL, accounting for 89.88%, which was significantly increased. Switched memory B-cell counts were 13.46/µL, accounting for 4.41%, indicating an obvious reduction. The rest of the blood work was negative. During hospitalization, bacterial (including tuberculosis) and viral (cytomegalovirus, Epstein-Barr virus) infections, parasitic infestations and celiac disease were excluded.

Gastrointestinal endoscopy, which was performed after admission, revealed multiple irregular ulcers in the ileum, bulb, and duodenum that were partially covered with white exudates. There was dense polyp proliferation with the formation of mucosal bridges in the descending colon, transverse colon, ascending colon and ileocecal region (Figure 1A). The same result was found in small bowel capsule endoscopy, revealing multiple ulcers and diminutive polyps. Histopathological examination revealed chronic inflammation of the mucosa with ulceration and epithelioid cell granulomas without caseous necrosis.

Figure 1 Endoscopy images of the patient. (A) Densely polyp proliferation with formation of mucosal bridges at the onset; (B) multiple polyp proliferations after initial treatment.

The patient was diagnosed with CD with a phenotype of A1b, L3 + L4a + L4b, B1, or G0 according to the Paris classification. In addition to antibiotics and nutritional support, she received 2 rounds of infliximab treatment on the basis of the IBD guidelines, forced to abort soon because of severe allergic reactions and changed to steroids 1 mg/kg daily. Due to the limited efficacy of the initial treatment, adalimumab was administered every other week, in conjunction with immunosuppressive agents such as azathioprine at a dosage of 1–1.5 mg/day.

After three months of treatment, comprising a total of eight administrations of adalimumab, the patient continued to experience persistent fever and recurrent abdominal pain. Laboratory evaluations indicated elevated erythrocyte sedimentation rates and CRP levels, along with a persistent decline in albumin levels. The patient’s Pediatric Crohn’s Disease Activity Index (PCDAI) was recorded at 45 points. Endoscopic reexamination revealed exacerbated lesions in the colon, and large numbers of polyps and ulcers resulted in stenosis in the ascending colon. The cavity was so narrow that the endoscope could not pass through it (Figure 1B). Pathology results still revealed moderate chronic inflammation and many epithelioid granulomas.

Other underlying conditions, such as immunodeficiency or gene defects, were considered. This was confirmed via further whole-exon sequencing, which confirmed the presence of compound heterozygous mutations in the LRBA gene (c.2401C>T, not previously reported, and c.5149G>A), with uncertain pathogenicity scores (Figure 2). Protein 3D structure (5) modeling (Figure 3) demonstrated that, compared to the wild-type LRBA protein, the p.V1717M mutant (c.5149G>A) exhibited an incomplete structure, while the p.H801Y mutant (c.2401C>T) showed significant structural alterations.

Figure 2 Genetic testing results of the patient. Sanger sequencing confirmed the presence of a mutation in exon 20/30 (c.2401C>T/c.5149G>A; p.H801Y/p.V1717M) of the LRBA gene in patient. The red arrowheads indicate mutation locations. The patient’s mother and father are both carriers with a heterozygous variant. LRBA, lipopolysaccharide-responsive beige-like anchor protein.
Figure 3 The protein 3D structure modeling was constructed using I-TASSER (5) software, and the amino acid valine at position 1,717 of the wild type was changed to methenamine from valine, and the amino acid histidine at position 801 of the wild type was changed to tyrosine from histidine.

Considering the poor benefit of the previous regimen, the therapeutic approach was modified to include adalimumab administered weekly and methotrexate (MTX) at a dosage of 15 mg/m2 per week. This was accompanied by an adjustment in the formulation to lactose-free milk for total enteral nutrition. These changes resulted in significant alleviation of symptoms and improved findings on colonoscopy (Figure 4), as quantified by the PCDAI and the Crohn’s Disease Endoscopic Index of Severity (CDEIS) (see Table 1). The patient is currently under ongoing follow-up, with no notable discomfort reported.

Figure 4 The endoscopy image of the patient post-treatment, indicating that mucosal inflammation was relieved with decreased polyps in the colon.

Table 1

The clinical/laboratory/endoscopic manifestation of patients in the timeline for diagnosis and subsequent therapy adjustments

Time Clinical symptom Laboratory tests PCDAI Colonoscopy CDEIS
The time for diagnosis Abdominal pain, diarrhea (3–4 times daily) ESR 59 mm/h; Hb 93 g/L, CRP 45.65 mg/L; albumin 28.3 g/L 45 22.2 (Figure 1A)
Prior to therapy adjustment Fever, abdominal pain, diarrhea (1–2 times daily) ESR 44 mm/h; Hb 109 g/L, CRP 27.56 mg/L; albumin 27.2 g/L 42.5 25.75 (Figure 1B)
One month post-adjustment No All normal 0 –
2 months post-adjustment No All normal 0 3.8
3 months post-adjustment No All normal 0 –
6 months post-adjustment No All normal 0 –
12 months post-adjustment No All normal 0 1.9 (Figure 4)

CDEIS, Crohn’s Disease Endoscopic Index of Severity; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; Hb, hemoglobin; PCDAI, Pediatric Crohn’s Disease Activity Index.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent for publication of this case report and accompanying images was not obtained from the patient or the relatives after all possible attempts were made.

Literature review

Twenty-eight publications were reviewed as a result of a stringent selection of previous cases with a diagnosis of LRBA deficiency and IBD, in which gastrointestinal (GI) manifestations were directly marked as IBD or IBD-like by the authors (including “ulcerative colitis”, “crohn’s disease”, and “granulomatous colitis”). Among these 18 patients who suffered from IBD (4,6-14), those with LRBA deficiency were identified (Table 2).

Table 2

The basic information of patients with a diagnosis of LRBA deficiency and IBD

Patient number Age of onset Sex Homozygous/heterozygous DNA Endoscopic findings Pathological characteristics Clinical feature (other system) Treatment Effective therapy Reference
1 2.4 years Unknown Homozygous c.2445_2447del(C)3ins(C)2, p.P86Lfs*4 Inflamed mucosa of stomach, duodenum, ileum and colon Colitis with lymphoid infiltration, erosive ileitis Lymphadenopathy, autoimmune thrombocytopenia, diabetes mellitus, autoimmune thyroiditis AZA, sirolimus, steroids, tacrolimus, abatacept HSCT (6)
2 1.2 years Unknown Heterozygous c.3647_3651delCTAA; c.7937T>G: I2646S Gastritis, ileum and colon without signs of inflammation Atrophic gastritis and auto-immune colitis Vitiligo, polyarthritis, autoimmune granulocytopenia, hemolytic anaemia, thrombocytopenia AZA, CSA, MTX, sirolimus, steroids HSCT (6)
3 17.4 years Unknown Homozygous c.6862lT, p.Tyr2288Metfs*29 Stomach and colon without signs of inflammation Gastritis, colonic lymphoid infiltration Eczema, vitiligo, autoimmune thyroiditis, autoimmune polyserositis, alopecia Steroids, abatacept HSCT (6)
4 4.1 weeks Male – c.6230C>A, p.Ala2077Asp – – Bronchiectasis, sepsis, pancytopenia, hypotonia, pericardial effusion, encephalomalacia, diffuse mesangial sclerosis IVIG Dead (7)
5 5 years Male Heterozygous c.1399A>G, pMet467Val Uniform colonic ulceration and friability Severe chronic active colitis, without granulomas Hypogammaglobulinemia Infliximab (interruption due to infection), CS, vedolizumab, sirolimus (interruption due to idiopathic intracranial hypertension), abatacept, intermittent rectal budesonide Abatacept (monthly) (8)
6 3 months Male Homozygous c.7434A>G, p.Asp 248Gly; c.5083G>C, p.Val1695Leu Mild colitis Mild villous blunting; nonspecific colitis No HSCT HSCT (9)
7 5 months Female Homozygous c.544C>T, p.Arg182Ter Normal No cryptitis, granuloma Anasarca, oral thrush, ulcers in mouth Elemental formula, steroids, AZA Lost to follow-up (9)
8 1.63 years Male Heterozygous p.V737I – – No – – (10)
9 9.33 years Male Heterozygous p.E1916X – – No HSCT – (10)
10 4.5 years Male Homozygous c.675G>A, p.W225* – – AIHA, ITP, thyroiditis, splenomegaly Steroids, CSA, MMF, abatacept, HSCT Abatacept, HSCT (4)
11 6 years Male Homozygous c.5527delT, p.C1843Afs*2 – – AIHA, thyroiditis, splenomegaly Steroids, CSA, MMF, abatacept, IVIG, HSCT Abatacept, HSCT (4)
12 1 year Female Homozygous c.5504delT, p.L1835fs*1 – – ITP, AIHA, splenomegaly Steroids, CSA, MMF, abatacept, IVIG Abatacept (4)
13 1 year Male Homozygous c.2893_2900delinsGCCAG ATATATATATATATATATATATA, p.I964Afs*32 – – Splenomegaly Steroids, ASA, CSA, MMF, abatacept,
IVIG, HSCT		 HSCT (4)
14 16 years Female Homozygous c.175G>T, P.E59* – – Splenomegaly, non-Hodgkin lymphoma B cell Steroids, ASA, splenectomy, IVIG Dead (4)
15 9.5 months Female Homozygous c.1570 G>A, p.G524S – – No MSLZ, CS MSLZ, CS, and thalidomide (11)
16 6 weeks Male Heterozygous c.3647_3651delCTAA Antiparietal cell-positive autoimmune gastritis, autoimmune colitis Atrophy, metaplasia, and endocrine cell hyperplasia, lymphofollicular hyperplasia, increased epithelial regeneration, and increased apoptosis without any signs of infectious agents Progressive vitiligo, aseptic polyarthritis, autoimmune thrombocytopenia Gluten-free diet, CSA, high doses of steroids, sirolimus, AZA, and multiple courses of rituximab, a combination of rituximab, sirolimus, and an escalated dosage of steroid (prednisolone, 2 mg/kg/day) HSCT (12)
17 6 months Female Homozygous c.A8470C, c.T8471C, p.Ile2824Pro – Diffuse villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis in duodenum, crypt epithelium injury and regenerative inflammation in colon Autoimmune thyroiditis, edema, type 1 diabetes mellitus Gluten-free diet, steroid, CSA No (13)
18 7.1 years Female Homozygous c.1570G>A Ulcers in gastrointestinal tract resembling Crohn’s disease-like colitis – No Steroids, 5-ASA, AZA 5-ASA, AZA (14)

AIHA, autoimmune hemolytic anemia; ASA, acetylsalicylic acid; AZA, azathioprine; CS, corticosteroids; CSA, cyclosporine A; HSCT, hematopoietic stem cell transplantation; IBD, inflammatory bowel disease; ITP, immune thrombocytopenia; IVIG, intravenous immunoglobulin; LRBA, lipopolysaccharide-responsive beige-like anchor protein; MMF, mycophenolate mofetil; MSLZ, mesalazine; MTX, methotrexate.

The age at first presentation ranged from 4.1 weeks to 17.4 years. The male/female ratio was 3/2 among the available data. All patients were diagnosed with IBD or IBD-like colitis, and most of them had accompanying autoimmune diseases. Ten patients had endoscopic or pathological findings, showing variable degrees of inflammation with or without ulcers and mucosal friability. Lymphocytic infiltration was mentioned frequently in pathology, and cryptitis was partially visible without granulomas. Each patient was found to have different genomic mutations. The treatments are diverse and include elemental formulas, mesalazine (MSLZ), acetylsalicylic acid (ASA), azathioprine (AZA), sirolimus, corticosteroids (CS), tacrolimus, cyclosporine A (CSA), MTX, infliximab, adalimumab, vedolizumab, rituximab, mycophenolate mofetil (MMF), abatacept, intravenous immunoglobulin (IVIG) and hematopoietic stem cell transplantation (HSCT), among which abatacept and HSCT are the most effective.

Discussion

Traditional IBD is thought to be a polygenic disease. Genome-wide association studies have identified a number of gene loci associated with diseases, among which single variation has a minimal impact on heritability (15,16). However, through NGS technology in some younger patients (especially very early-onset IBD patients), several specific gene disorders have been found to be the underlying cause of IBD, and a single gene mutation can lead to endoscopic and microscopic findings similar to or identical to those observed in conventional IBD. There are approximately 75 genetic variants associated with IBD to date, collectively called monogenic IBDs (17). The LRBA gene was first reported in 2012 (15,18) and is located on chromosome 4q31.3. Biallelic loss-of-function mutations in the LRBA gene are associated with primary immunodeficiency and IBD (19). The pathogenesis leading to intestinal pathology in monogenic IBD is proposed to differ from that in conventional IBD. Immune cell defects associated with primary immunodeficiency led to intestinal injury. Defective T-cell immune tolerance is one of the common pathophysiological mechanisms underlying intestinal immune homeostasis alteration, as is the mechanism underlying LRBA deficiency (20). The cell-surface expression of the protein cytotoxic T lymphocyte antigen 4 (CTLA4), a negative regulator of T-cell proliferation, is regulated by LRBA, which was proven by studies showing decreased CTLA4 protein levels within regulatory and conventional T cells isolated from LRBA-deficient patients compared with those seen in analogous T cells from healthy controls (20,21).

Key findings

In this study, we described a patient with concomitant active CD and LRBA deficiency who carried a novel mutation (c.2401C>T), and the other mutation was reported without certain significance. Hematological examination revealed changes in B cells, showing raised naive B-cells and decreased switch memory B-cells, which is consistent with previous reports on LRBA pediatric patients (3,4). Endoscopy revealed multiple irregular ulcers and dense polyp proliferation with the formation of mucosal bridges. Under combined therapy with adalimumab and MTX, the clinical and endoscopic situation is well controlled.

Strengths and limitations

As one of the most common early manifestations of LRBA deficiency, enteropathy has been reported in multiple cases, among which IBD or IBD-like colitis is rare (22,23). In summary, the microscopic findings of the majority of patients suggest mild inflammation, with no granulomatous appearance observed. However, this particular pediatric patient exhibited significant granulomas accompanied by mucosal bridging. A review of the literature revealed that some LRBA patients have granulomatous complications, but current reports mostly pertain to the lungs (3,4). Further clarification is needed with a larger number of cases.

Comparison with similar research

Monogenic IBD may not respond to conventional therapies and may require novel therapies. A number of therapeutic strategies have been mentioned in the literature. Abatacept is a CTLA-4 immunoglobulin fusion protein that regulates the immune system by mimicking the biological function of CTLA-4, which plays an important role in the treatment of diseases associated with LRBA defects. Deficiencies in LRBA can lead to depressed function of Treg cells, leading to immune disorders and autoimmune responses (20), which can be inhibited by abatacept through binding to CD80 and CD86 on the surface of antigen-presenting cells and preventing T-cell activation by blocking the T-cell costimulatory pathway (24). LRBA deficiency is also associated with impaired mTOR/S6K signaling in T cells (25). Unsurprisingly, an mTOR inhibitor (sirolimus) is a targeted therapy for LRBA deficiency that helps improve Treg cell function (26) and has been used in IPEX and its phenocopies (27). Research indicates that children who exhibit poor responses to medical therapy might benefit from colectomy and HSCT (28). However, in this specific case, the child was effectively managed with a combination of biologic therapy and immunosuppressive agents.

Explanations of findings

The defect in the LRBA gene is strongly associated with various functional disorders of the immune system, particularly affecting B cell proliferation and function. In this patient, blood tests revealed an increased number of naive B cells and a reduced number of switched memory B cells. The absence or malfunction of the LRBA protein may lead to B cells’ inability to respond appropriately to external stimuli, thereby impairing their proliferation and differentiation (29). Research has demonstrated that the LRBA protein is crucial for maintaining B-cell homeostasis by regulating BCR-NF-κB signaling. This regulation is essential, as its disruption can lead to alterations in the NF-κB pathway. For instance, while wild-type B cells exhibit transient activation of NF-κB following BCR cross-linking, B cells deficient in LRBA protein are unresponsive and display a proliferation rate that is only 56% of that observed in wild-type B cells. This deficiency may contribute to the observed decrease in switched memory B cells (30).

Implications and actions needed

In conclusion, we should be aware of the possibility of LRBA deficiency for IBD patients showing unsatisfactory treatment efficacy, and biologic therapy may lead to clinical remission.

Conclusions

We described a Chinese IBD and LRBA-deficient patient carrying a novel mutation. In this context, the patient achieved remission under regular biologic therapy, which may offer valuable insights for the treatment of similar cases.

Acknowledgments

We are thankful to our patient and her family. We appreciate our laboratory staff Xiaoli Shu and our nurses.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://tp.amegroups.com/article/view/10.21037/tp-2024-567/rc

Peer Review File: Available at https://tp.amegroups.com/article/view/10.21037/tp-2024-567/prf

Funding: This study was supported by China Crohn’s & Colitis Foundation (CCCF) (No. CCCF-QF-2022B04-4) and Zhejiang Provincial Medical Health Science and Technology Plan Project (No. 2024KY1171).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-2024-567/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent for publication of this case report and accompanying images was not obtained from the patient or the relatives after all possible attempts were made.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

  1. Sartor RB. Mechanisms of disease: pathogenesis of Crohn's disease and ulcerative colitis. Nat Clin Pract Gastroenterol Hepatol 2006;3:390-407. [Crossref] [PubMed]
  2. Sudan R, Fernandes S, Srivastava N, et al. LRBA Deficiency Can Lead to Lethal Colitis That Is Diminished by SHIP1 Agonism. Front Immunol 2022;13:830961. [Crossref] [PubMed]
  3. Habibi S, Zaki-Dizaji M, Rafiemanesh H, et al. Clinical, Immunologic, and Molecular Spectrum of Patients with LPS-Responsive Beige-Like Anchor Protein Deficiency: A Systematic Review. J Allergy Clin Immunol Pract 2019;7:2379-2386.e5. [Crossref] [PubMed]
  4. Cagdas D, Halaçlı SO, Tan Ç, et al. A Spectrum of Clinical Findings from ALPS to CVID: Several Novel LRBA Defects. J Clin Immunol 2019;39:726-38. [Crossref] [PubMed]
  5. Yang J, Zhang Y. I-TASSER server: new development for protein structure and function predictions. Nucleic Acids Res 2015;43:W174-81. [Crossref] [PubMed]
  6. Moser LM, Fekadu J, Willasch A, et al. Treatment of inborn errors of immunity patients with inflammatory bowel disease phenotype by allogeneic stem cell transplantation. Br J Haematol 2023;200:595-607. [Crossref] [PubMed]
  7. Lee WI, Chen CC, Chen SH, et al. Clinical Features and Genetic Analysis of Taiwanese Primary Immunodeficiency Patients with Prolonged Diarrhea and Monogenetic Inflammatory Bowel Disease. J Clin Immunol 2023;43:1455-67. [Crossref] [PubMed]
  8. He M, Wong A, Sutton K, et al. Very-Early Onset Chronic Active Colitis with Heterozygous Variants in LRBA1 and CARD11, a Case of "Immune TOR-Opathies". Fetal Pediatr Pathol 2023;42:297-306. [Crossref] [PubMed]
  9. Nambu R, Warner N, Mulder DJ, et al. A Systematic Review of Monogenic Inflammatory Bowel Disease. Clin Gastroenterol Hepatol 2022;20:e653-63. [Crossref] [PubMed]
  10. Crowley E, Warner N, Pan J, et al. Prevalence and Clinical Features of Inflammatory Bowel Diseases Associated With Monogenic Variants, Identified by Whole-Exome Sequencing in 1000 Children at a Single Center. Gastroenterology 2020;158:2208-20. [Crossref] [PubMed]
  11. Ye Z, Zhou Y, Huang Y, et al. Phenotype and Management of Infantile-onset Inflammatory Bowel Disease: Experience from a Tertiary Care Center in China. Inflamm Bowel Dis 2017;23:2154-64. [Crossref] [PubMed]
  12. Bakhtiar S, Gámez-Díaz L, Jarisch A, et al. Treatment of Infantile Inflammatory Bowel Disease and Autoimmunity by Allogeneic Stem Cell Transplantation in LPS-Responsive Beige-Like Anchor Deficiency. Front Immunol 2017;8:52. [Crossref] [PubMed]
  13. Serwas NK, Kansu A, Santos-Valente E, et al. Atypical manifestation of LRBA deficiency with predominant IBD-like phenotype. Inflamm Bowel Dis 2015;21:40-7. [Crossref] [PubMed]
  14. Tang WJ, Hu WH, Huang Y, et al. Potential protein-phenotype correlation in three lipopolysaccharide-responsive beige-like anchor protein-deficient patients. World J Clin Cases 2021;9:5873-88. [Crossref] [PubMed]
  15. Lopez-Herrera G, Tampella G, Pan-Hammarström Q, et al. Deleterious mutations in LRBA are associated with a syndrome of immune deficiency and autoimmunity. Am J Hum Genet 2012;90:986-1001. [Crossref] [PubMed]
  16. Alangari A, Alsultan A, Adly N, et al. LPS-responsive beige-like anchor (LRBA) gene mutation in a family with inflammatory bowel disease and combined immunodeficiency. J Allergy Clin Immunol 2012;130:481-8.e2. [Crossref] [PubMed]
  17. Nameirakpam J, Rikhi R, Rawat SS, et al. Genetics on early onset inflammatory bowel disease: An update. Genes Dis 2020;7:93-106. [Crossref] [PubMed]
  18. Jostins L, Ripke S, Weersma RK, et al. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 2012;491:119-24. [Crossref] [PubMed]
  19. Picard C, Al-Herz W, Bousfiha A, et al. Primary Immunodeficiency Diseases: an Update on the Classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency 2015. J Clin Immunol 2015;35:696-726. [Crossref] [PubMed]
  20. Lo B, Zhang K, Lu W, et al. AUTOIMMUNE DISEASE. Patients with LRBA deficiency show CTLA4 loss and immune dysregulation responsive to abatacept therapy. Science 2015;349:436-40. [Crossref] [PubMed]
  21. Uhlig HH, Charbit-Henrion F, Kotlarz D, et al. Clinical Genomics for the Diagnosis of Monogenic Forms of Inflammatory Bowel Disease: A Position Paper From the Paediatric IBD Porto Group of European Society of Paediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr 2021;72:456-73. [Crossref] [PubMed]
  22. Cagdas D, Halaçlı SO, Tan Ç, et al. A Spectrum of Clinical Findings from ALPS to CVID: Several Novel LRBA Defects. J Clin Immunol 2019;39:726-38. [Crossref] [PubMed]
  23. Mozdarani H, Kiaee F, Fekrvand S, et al. G2-lymphocyte chromosomal radiosensitivity in patients with LPS responsive beige-like anchor protein (LRBA) deficiency. Int J Radiat Biol 2019;95:680-90. [Crossref] [PubMed]
  24. Jung S, Gámez-Díaz L, Proietti M, et al. "Immune TOR-opathies," a Novel Disease Entity in Clinical Immunology. Front Immunol 2018;9:966. [Crossref] [PubMed]
  25. Kolukısa B, Barış S. Primary Immune Regulatory Disorders and Targeted Therapies. Turk J Haematol 2021;38:1-14. [Crossref] [PubMed]
  26. Battaglia M, Stabilini A, Tresoldi E. Expanding human T regulatory cells with the mTOR-inhibitor rapamycin. Methods Mol Biol 2012;821:279-93. [Crossref] [PubMed]
  27. Kucuk ZY, Bleesing JJ, Marsh R, et al. A challenging undertaking: Stem cell transplantation for immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. J Allergy Clin Immunol 2016;137:953-5.e4. [Crossref] [PubMed]
  28. Engelhardt KR, Shah N, Faizura-Yeop I, et al. Clinical outcome in IL-10- and IL-10 receptor-deficient patients with or without hematopoietic stem cell transplantation. J Allergy Clin Immunol 2013;131:825-30. [Crossref] [PubMed]
  29. Al Sukaiti N, AbdelRahman K, AlShekaili J, et al. Agammaglobulinaemia despite terminal B-cell differentiation in a patient with a novel LRBA mutation. Clin Transl Immunology 2017;6:e144. [Crossref] [PubMed]
  30. Flores-Hermenegildo JM, Hernández-Cázares FJ, Pérez-Pérez D, et al. Lrba participates in the differentiation of IgA+ B lymphocytes through TGFβR signaling. Front Immunol 2024;15:1386260. [Crossref] [PubMed]
Cite this article as: Wang Z, Fang Y, Yu J, Chen J, Luo Y. Loss-of-function of lipopolysaccharide-responsive beige-like anchor protein causes inflammatory bowel disease—a case report and literature review. Transl Pediatr 2025;14(6):1344-1352. doi: 10.21037/tp-2024-567

Article Options

Download Citation

Share