Two Faces of LRBA Deficiency in Siblings: Hypogammaglobulinemia and Normal Immunoglobulin Levels

Azizi, Gholamreza; Abolhassani, Hassan; Habibi, Sima; T, Rahamooz; Mohammadi, Hamed; Jafarnezhad-Ansariha, Fahimeh; Mortazavi-Jahromi, Seyed Shahabeddin; Yazdani, Reza; Aghamohammadi, Asghar

doi:10.18176/jiaci.0205

Cited by 18 publications

(9 citation statements)

References 8 publications

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“…All screening for CVID must include a physical examination. However, clinical symptoms can vary from patient to patient, even among affected family members with identical mutations in the same gene [142][143][144]. If physical examination and the clinical history lead to a suspicion of PID, a primary paraclinical evaluation should be undertaken (Figure).…”

Section: Diagnosismentioning

confidence: 99%

Common Variable Immunodeficiency: Epidemiology, Pathogenesis, Clinical Manifestations, Diagnosis, Classification, and Management

Yazdani¹,

Habibi²,

Sharifi³

et al. 2020

J Investig Allergol Clin Immunol

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105

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Common variable immunodeficiency (CVID) is a heterogeneous disorder characterized by hypogammaglobulinemia and increased susceptibility to recurrent bacterial infections. It is the most frequent symptomatic antibody deficiency, with a wide variety of infectious and noninfectious complications. Numerous studies have demonstrated that immunological and genetic defects are involved in the pathogenesis of CVID. However, in most cases, the genetic background of the disease remains unidentified. This review aims to discuss various aspects of CVID, including epidemiology, pathogenesis, symptoms, diagnosis, classification, and management.

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Section: Diagnosismentioning

confidence: 99%

Common Variable Immunodeficiency: Epidemiology, Pathogenesis, Clinical Manifestations, Diagnosis, Classification, and Management

Yazdani¹,

Habibi²,

Sharifi³

et al. 2020

J Investig Allergol Clin Immunol

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105

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“…2,[4][5][6][10][11][12][13] Until recently, the conventional treatment options for LRBA deficiency have included various immunosuppressive agents, such as corticosteroids, sirolimus, and abatacept (a soluble CTLA4 immunoglobulin fusion protein that appears to partially restore Treg-cell function). 5,6,9 One prospective study 14 and others 9,[15][16][17][18][19] reported on the effectiveness of the latter. However, soluble CTLA4 might not fully replace membrane-bound CTLA4 or other LRBA functions.…”

mentioning

confidence: 99%

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

Tesch

Abolhassani

Shadur

et al. 2020

Journal of Allergy and Clinical Immunology

118

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stem cell transplantation (HSCT) in patients with severe presentation of LPS-responsive beige-like anchor protein (LRBA) deficiency, but long-term follow-up and survival data beyond previous patient reports or meta-reviews are scarce for those patients who do not receive a transplant. Objective: This international retrospective study was conducted to elucidate the longitudinal clinical course of patients with LRBA deficiency who do and do not receive a transplant. Method: We assessed disease burden and treatment responses with a specially developed immune deficiency and dysregulation activity score, reflecting the sum and severity of organ involvement and infections, days of hospitalization, supportive care requirements, and performance indices. Results: Of 76 patients with LRBA deficiency from 29 centers (median follow-up, 10 years; range, 1-52), 24 underwent HSCT from 2005 to 2019. The overall survival rate after HSCT (median follow-up, 20 months) was 70.8% (17 of 24 patients); all deaths were due to nonspecific, early, transplant-related mortality. Currently, 82.7% of patients who did not receive a transplant (43 of 52; age range, 3-69 years) are alive. Of 17 HSCT survivors, 7 are in complete remission and 5 are in good partial remission without treatment (together, 12 of 17 [70.6%]). In contrast, only 5 of 43 patients who did not receive a transplant (11.6%) are without immunosuppression. Immune deficiency and dysregulation activity scores were significantly lower in patients who survived HSCT than in those receiving conventional treatment (P 5 .005) or in patients who received abatacept or sirolimus as compared with other therapies, and in patients with residual LRBA expression. Higher disease burden, longer duration before HSCT, and lung involvement were associated with poor outcome. Conclusion: The lifelong disease activity, implying a need for immunosuppression and risk of malignancy, must be weighed against the risks of HSCT.

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“…LRBA deficiency was firstly described to associate with early-onset hypogammaglobulinemia (8). However, later reports showed that not all of the LRBA mutant patients presented with hypogammaglobulinemia (9,10,15). In this study, the patient did not have hypogammaglobuline-Iran J Pediatr.…”

Section: Discussionmentioning

confidence: 56%

“…A higher frequency of these clinical manifestations was reported in a large Iranian cohort with LRBA deficient patients, which might be due to a longer follow-up period (3). Interestingly it has been reported that affected siblings with a same genetic defect in LRBA gene had different clinical manifestations, which highlights its potential role of as yet an unidentified modifier gene (15). In fact, because of the diversity of the clinical symptoms, there is still no standard diagnosis for LRBA deficiency (10).…”

Section: Discussionmentioning

confidence: 99%

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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Two Faces of LRBA Deficiency in Siblings: Hypogammaglobulinemia and Normal Immunoglobulin Levels

Cited by 18 publications

References 8 publications

Common Variable Immunodeficiency: Epidemiology, Pathogenesis, Clinical Manifestations, Diagnosis, Classification, and Management

Common Variable Immunodeficiency: Epidemiology, Pathogenesis, Clinical Manifestations, Diagnosis, Classification, and Management

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

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

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