New therapeutic approach by sirolimus for enteropathy treatment in patients with LRBA deficiency

Azizi, Gholamreza; Abolhassani, Hassan; Yazdani, Reza; Mohammadikhajehdehi, Sara; Parvaneh, Nima; Negahdari, Babak; Mohammadi, Javad; Aghamohammadi, Asghar

doi:10.23822/eurannaci.1764-1489.22

Cited by 32 publications

(18 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Individualized medications (anti‐inflammatory and immunosuppressive drugs, biological agents, and monoclonal antibody) used for autoimmune and inflammatory complications in patients with LRBA deficiency are shown in Supporting Information Table S4. Sirolimus was the last therapeutic approach for management of enteropathy in six patients (Azizi, Abolhassani, Yazdani, et al, ). Although LRBA‐deficient patients who received “monoclonal antibody, immunosuppressive and/or biological agents” had lower lymphocyte counts than other patients (median [IQR]: 2000 [1720–3300 vs. 2400 [2370–3800] cell/µl; p = 0.212), no difference was noted between the frequency of CD4 + T cells in LRBA‐deficient patients who received this type of therapy and those who did not (median [IQR]: 23.80 [7.17–46.10] vs. 28.85 [18.22–45.25]; p = 0.775).…”

Section: Resultsmentioning

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

View full text Add to dashboard Cite

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.

show abstract

Section: Resultsmentioning

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

View full text Add to dashboard Cite

show abstract

“…In our case, sirolimus had been used with partial benefit on the ALPS-like lymphoproliferation, even if previous reports showed promising results (34). Only abatacept allowed a consistent and persistent improvement of the gastritis, allowing weaning from glucocorticoids and proton pump inhibitors.…”

Section: Discussionmentioning

confidence: 75%

Case Report: Refractory Autoimmune Gastritis Responsive to Abatacept in LRBA Deficiency

et al. 2021

View full text Add to dashboard Cite

Primary immunodeficiency (PID) with immune dysregulation may present with early onset gastrointestinal autoimmune disorders. When gastrointestinal autoimmunity is associated with multiple extraintestinal immune system dysfunction the diagnosis of PID is straightforward. However, with the advent of next generation sequencing technologies, genetic defects in PID genes have been increasingly recognized even when a single or no extraintestinal signs of immune dysregulation are present. A genetic diagnosis is especially important considering the expanding armamentarium of therapies designed to inhibit specific molecular pathways. We describe a boy with early-onset severe, refractory autoimmune gastritis and biallelic mutations in the LRBA gene causing a premature STOP-codon who was successfully treated with CTLA4-Ig, abatacept, with long term clinical and endoscopic remission. The case underscores the importance to consider a monogenetic defect in early onset autoimmune disorders, since the availability of targeted treatments may significantly improve patient prognosis.

show abstract

“…Sirolimus is well known for its effectiveness in treating autoimmune cytopenias [29, 30]. Azizi et al described the use of sirolimus for multiple drug resistant LRBA enteropathy [31]. Our patient’s life-threatening hemolytic anemia responded rapidly to sirolimus, although she did develop other autoimmune manifestations years later requiring additional therapies.…”

Section: Discussionmentioning

confidence: 80%

Arthritis in children with LRBA deficiency – case report and literature review

Tesher

2019

Pediatr Rheumatol

View full text Add to dashboard Cite

BackgroundLipopolysaccharide (LPS)-responsive and beige like anchor (LRBA) deficiency is categorized as a subtype of common variable immune deficiency (CVID). A growing number of case reports and cohorts reveal a broad spectrum of clinical manifestations and variable phenotype expression, including immune dysregulation, enteropathy and recurrent infections. The association between rheumatic disease and CVID generally has been well established, arthritis has been less frequently reported and minimal data regarding its clinical features and characteristic in LRBA deficiency has been published. This case report and literature review evaluates the characteristics and features of arthritis in LRBA deficiency patients.Case presentation and review resultsHerein, we describe a unique case of LRBA deficiency first presented with poly articular arthritis. Alongside the report, a literature review focusing on LRBA deficiency, rheumatic disease and arthritis has been conducted. We reviewed 43 publications. Among these, 7 patients were identified with arthritis. Age of first presentation was six weeks to 3 years. Male to female ratio was 4/3. Two patients were diagnosed with polyarticular Juvenile idiopathic arthritis (JIA) and three with oligoarticular JIA. Each patient was found to have different genomic mutation. The treatment was diverse and included corticosteroids, cyclosporine, methotrexate, adalidumab and abatacept.ConclusionJoint involvement is variable in LRBA deficiency, hence it should always be kept in mind as a differential diagnosis for a patient with combination of juvenile arthritis and clinically atypical immune dysregulation and / or immunodeficiency.

show abstract

New therapeutic approach by sirolimus for enteropathy treatment in patients with LRBA deficiency

Cited by 32 publications

References 23 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

Case Report: Refractory Autoimmune Gastritis Responsive to Abatacept in LRBA Deficiency

Arthritis in children with LRBA deficiency – case report and literature review

Contact Info

Product

Resources

About