Background: Common variable immunodeficiency (CVID), is generally recognized as the most frequent type of Symptomatic primary immunodeficiencies (PID). Mutations in lipopolysaccharide-responsive beige-like anchor protein (LRBA) gene, are the most common genetic alterations amongst CVID patients. To date, there are no published studies to compare clinical and immunologic features of LRBA-deficient patients with those who do not harbor any known genetic mutations. Therefore, this study aims to compare the clinical manifestations and laboratory findings of Iranian patients with LRBA-deficiency and CVID with no known genetic alterations. Methods: We performed a longitudinal study on patients who had been diagnosed with CVID. Demographic and clinical features were obtained via the databank of the Iranian Registry of Primary Immunodeficiencies, and the direct interviews with patients. To assess the presence of LRBA or other genetic mutations, wholeexome sequencing (WES) was used. Immunologic characteristics of patients were evaluated using flow cytometry, nephelometry, and conventional blood counts. The current study is conducted at Tehran’, s Children Medical Center and is approved by the ethics committee of Tehran University of Medical Sciences. Results: Between March 2013 and October 2019, we enrolled 30 patients with LRBA-deficiency and 13 patients with CVID, who had no identified genetic mutations. Regarding clinical features, there were no significant differences for the prevalence of infections at different sites (lung, sinuses, and middle ear) among the two groups (all P > 0. 05). However, the incidences of autoimmune disorders and enteropathy were significantly higher among LRBA-deficient cases (P < 0. 001). In serum levels of immunoglobulins, there were significant differences for IgG and IgM between the two groups (P of 0. 014 and 0. 004, respectively),however, this was not seen for IgA and IgE levels. Likewise, we did not see any significant differences for the cluster of differentiation (CD) markers between the two groups (all P > 0. 05). Conclusion: Compared to the CVID patients with no identified genetic mutations, LRBA-deficient patients have a significantly greater chance of parental consanguinity and developing autoimmune disorders and enteropathy, and have significantly higher values of serum IgG and IgM. The rate of infectious complications and other basic laboratory features, do not show significant differences between the two groups.

Background: Lipopolysaccharide-responsive beige-like anchor (LRBA) deficiency is an inborn error of immunity characterized by a heterogeneous spectrum of manifestations, including enteropathy, immune dysregulation, and autoimmune disorder. Joint involvement has been less frequently reported, and limited data regarding its clinical presentation in LRBA deficiency has been published. Case presentation and review results: We reported an Iranian girl who was initially presented with recurrent respiratory tract infections and otitis media, later complicated by arthritis, growth failure, and organomegaly. The diagnosis of LRBA deficiency was confirmed by the identification of a novel homozygous missense variant in the LRBA gene (c. 7742T>A, p. M2581K). Along with this report, a literature review focused on joint involvement, on 26 patients with LRBA deficiency was performed. Conclusion: Non-infectious manifestations such as joint involvement have a broad spectrum in LRBA deficiency. For the timely diagnosis and appropriate clinical management, LRBA deficiency should always be kept in mind as a differential diagnosis in patients with joint involvement and clinically typical immune dysregulation.

Biallelic lipopolysaccharide-responsive and beige-like anchor (LRBA) mutations could lead to an immune dysregulation disorder, labeled as LRBA deficiency. A wide spectrum of clinical manifesta tion was shown to be associated with recurrent infections, enteropathy, hypogammaglobulinemia, and autoimmune complications. Notably, LRBA interacts with cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) by its recycling to the T-cell surface. Accordingly, LRBA deficiency abolishes CTLA4 protein expression. In this study, we presented a case with a homozygous mutation in the LRBA gene as well as a normal level of CTLA4 protein. In this regard, the immunologist assays of this patient revealed low immunoglobulin levels, CD4+ helper T cells, and CD19+ B cells.