Comparison of Clinical Manifestations, Immunological Analyses Between LRBA and CVID Patients: A Longitudinal Study

Javad Tafaroji; Pouya Mahdavi Sharif; Saeed Karimi; Ali Reza Sharifi

doi:10.18502/igj.v4i1.8393

Javad Tafaroji Department of Pediatrics, Qom University of Medical Sciences, Qom, Iran
Pouya Mahdavi Sharif School of medicine, Tehran University of Medical Sciences, Tehran, Iran.
Saeed Karimi Student of Qom university of Medical Sciences, Qom, Iran.
Ali Reza Sharifi MD Student, Student Research Committee, Qom University of Medical Sciences, Qom, Iran.

DOI: https://doi.org/10.18502/igj.v4i1.8393

Keywords: Common Variable Immunodeficiency; Lipopolysaccharide-responsive Beige-Like Anchor Protein; Immunodeficiency; Autoimmunity; IBD-Like Syndrome; Enteropathy

Abstract

Background: Common variable immunodeficiency (CVID), is generally recognized as the most frequent type of Symptomatic primary immunodeficiencies (PID). Mutations in lipopolysaccharideresponsive 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, whole-exome 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-values > 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-values 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-values > 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.