Polyautoimmunity in Patients with LPS-Responsive Beige-Like Anchor (LRBA) Deficiency

Azizi, Gholamreza; Abolhassani, Hassan; Zaki‐Dizaji, Majid; Habibi, Sima; Mohammadi, Hamed; Shaghaghi, Mohammadreza; Yazdani, Reza; Anaya, Juan Manuel; Rezaei, Nima; Hammarström, Lennart; Aghamohammadi, Asghar

doi:10.1080/08820139.2018.1446978

Cited by 18 publications

(18 citation statements)

References 42 publications

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“…Patients with LRBA deficiency present a variety of clinical symptoms, including recurrent infections, lymphoproliferations, allergic symptoms, neurological problems, chronic diarrhea, and autoimmunities (Alkhairy et al, ; Azizi, Abolhassani, Asgardoon, et al, ; Azizi, Abolhassani, Mahdaviani, et al, ; Azizi, Tavakol, et al, ). However, prevalent symptoms are autoimmune cytopenias and enteropathy (Azizi, Abolhassani, et al, ; Azizi, Habibi, et al, ; Levy et al, ). The immunological abnormalities reported in LRBA‐deﬁcient patients were early‐onset hypogammaglobulinemia, decreased specific antibody production, and low B‐cell subset counts, as well as a defect in the frequency and function of CD4 + T cells (Azizi, Abolhassani, Mahdaviani, et al, ; Azizi, Rezari, et al, ; Azizi, Abolhassani, et al, ; Azizi, Habibi, et al, ).…”

Section: Introductionmentioning

confidence: 99%

The imbalance of circulating T helper subsets and regulatory T cells in patients with LRBA deficiency: Correlation with disease severity

Azizi

Mirshafiey

Abolhassani

et al. 2018

Journal Cellular Physiology

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Patients with lipopolysaccharides responsive beige-like anchor protein (LRBA) deficiency suffer from a variety of immunological abnormalities. In the current study, we investigated the role of T helper (Th) cell subsets and regulatory T (Treg) cells and their related cytokines and transcription factors in the immune dysregulation of LRBA deficiency. The study population comprised of 13 LRBA-deficient patients and 13 age- and sex-matched healthy controls (HCs). Th subsets and Treg were examined by flow cytometry. The expression of determinant cytokines (interferon-γ [IFN-γ], interleukin [IL]-17, IL-22, and IL-10), and cell subset-specific transcription factors were evaluated before and after proliferation and activation stimuli. The frequencies of Th1, Th1-like Th17 and Th22 cells along with the expression of T-box transcription factor (TBET) and runt-related transcription factor 1 (RUNX1) were significantly increased in patients with LRBA. Moreover, IFN-γ and IL-22 production in LRBA-deﬁcient CD4 T cells were elevated after lymphocyte stimulation, particularly in patients with enteropathy. However, CD4 CD25 FoxP3 CD127 cells were significantly decreased in LRBA-deficient patients compared with those of HCs, particularly in patients with autoimmunity. There was a negative correlation between the frequencies of CD4 CD25 FoxP3 CD127 cells and Th1-like Th17 cells in LRBA-deficient patients, and an overlapping phenotype of autoimmunity and enteropathy were observed in ~70% of patients. The frequency of Th17 cells was lower in patients with enteropathy, while Th1-like Th17 cells were higher than in those without enteropathy. Our findings demonstrated an imbalance in Th subsets, mainly in Th1-like Th17 and Treg cells and their corresponding cytokines in LRBA deficiency, which might be important in the immunopathogenesis of autoimmunity and enteropathy.

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Section: Introductionmentioning

confidence: 99%

The imbalance of circulating T helper subsets and regulatory T cells in patients with LRBA deficiency: Correlation with disease severity

Azizi

Mirshafiey

Abolhassani

et al. 2018

Journal Cellular Physiology

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“…Autoimmune disease, which is one of the most frequent clinical phenotypes in LRBA deficient patients, was reported to occur in 76.5% and 61% patient with LRBA deficiency previously (2, 3). The most common features included AIHA (autoimmune hemolytic anemia), ITP (immune thrombocytopenia), IBD (inflammatory bowel disease) and so on (4,10). In addition, the patient also had clinical presentations which have been frequently reported in LRBA patients previously, such as granulomatous lymphadenitis, sinusitis and oral candidiasis.…”

Section: Discussionmentioning

confidence: 81%

“…CD27+IgD+ and CD27+IgD-B cells represented non-switched memory B cells and switched memory B cells, respectively (14). 4 Iran J Pediatr. 2019; 29(2):e84691.…”

Section: B Cell Immunophenotypingmentioning

confidence: 99%

“…LPS-responsive beige-like anchor protein (LRBA) deficiency is a rare inherited common variable immunodeficiency (CVID) caused by loss-of-function mutations in LRBA gene. Affected individuals were usually reported to suffer from immune deficiency, lymphoproliferation and various organ-specific autoimmunity, which severely affected the patients' physical health and imposes a heavy economic burden on the patients (1)(2)(3)(4)(5).…”

Section: Introductionmentioning

confidence: 99%

“…Three papers were published almost at the same time to categorize LRBA deficiency as a common variable immunodeficiency (CVID), with autoimmunity and inflammation (1,8,9). However, its clinical spectrum has been extended with the increasing publications worldwide in the recent years, which included recurrent in-fections, hypogammaglobulinemia, inflammatory bowel disease, enteropathy, splenomegaly, hepatomegaly, lymphadenopathy, growth retardation, atopic skin disease, EBV infections and so on (1)(2)(3)(4)10). Immunologic testing showed that a majority of LRBA deficient patients had reduced total B cells and B cell subsets, as well as Treg cells (3,10,11).…”

Section: Introductionmentioning

confidence: 99%

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Systemic Vasculitis and High IgE Level in a Patient with LPS-Responsive Beige-Like Anchor (LRBA) Deficiency

Wang

Chen

et al. 2019

Iran J Pediatr

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Background: Mutations in LPS-responsive and beige-like anchor (LRBA) gene in patients were firstly described to associate with a syndrome of immune deficiency and autoimmunity in 2012. However, there was still no LRBA deficient patient reported in China. Objectives: We present a Chinese patient with heterozygous LRBA gene mutations with his clinical, immunological and genetic features. Methods: Patient's clinical data was collected and analyzed. Laboratory results included lymphocyte subsets analysis and immunoglobulin quantification. Targeted gene capture followed by next-generation sequencing was used to identify the gene mutations, and flow cytometry assay was used to analyze B cell immunophenotyping of this patient. Results: The patient mainly suffered from recurrent respiratory tract infections, EBV-associated lymphoproliferative disease and systemic vasculitis. Heterozygous LRBA gene mutations were identified in the patient, which were inherited from his parents, respectively. B cell immunophenotyping revealed that he had decreased total B cells, bone marrow progenitor B cell subsets (HSC, CLP, Pro-B and Pre-B cells), immature B cells, non-switched memory B cells, switched memory B cells and B1 cell subsets. Besides, he had extremely high level of IgE. Conclusions: Herein, we firstly report a patient with heterozygous LRBA gene mutations in China. LRBA might play an important role in B cell development.

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

et al. 2019

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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.

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Polyautoimmunity in Patients with LPS-Responsive Beige-Like Anchor (LRBA) Deficiency

Abstract: Mutation in LRBA gene is one of the causes of monogenic polyautoimmunity. Awareness of this association is important in order to make an early diagnosis and prompt treatment.

Cited by 18 publications

References 42 publications

The imbalance of circulating T helper subsets and regulatory T cells in patients with LRBA deficiency: Correlation with disease severity

The imbalance of circulating T helper subsets and regulatory T cells in patients with LRBA deficiency: Correlation with disease severity

Systemic Vasculitis and High IgE Level in a Patient with LPS-Responsive Beige-Like Anchor (LRBA) Deficiency

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

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