Clinical, Immunologic, and Molecular Spectrum of Patients with LPS-Responsive Beige-Like Anchor Protein Deficiency: A Systematic Review

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

“…8 Earlier studies reported that most patients with LRBA deficiency who have undergone hematopoietic stem cell transplantation (HSCT) achieved complete remission; however, the studies also detected higher transplant-related mortality (TRM) rates than have been seen in patients with other inborn errors of immunity. 5,8,20 No genotype-phenotype correlation has been detected, 2,4,5 but milder phenotypes with residual protein expression have been observed. Thus, doctors treating patients with LRBA deficiency need more information regarding whether and when to proceed with HSCT.…”

“…Background: Recent findings strongly support hematopoietic Abbreviations used CNS: Central nervous system CTLA4: Cytotoxic T-lymphocyte antigen 4 HSCT: Hematopoietic stem cell transplantation IDDA: Immune deficiency and dysregulation activity score IPEX: Immunodysregulation polyendocrinopathy enteropathy Xlinked LRBA: LPS-responsive beige-like anchor PR: Partial remission Treg: Regulatory T TRM: Transplant-related mortality WBC: White blood cell LPS-responsive beige-like anchor protein (LRBA) deficiency, first described in 2012, 1 is a severe primary immunodeficiency with a broad spectrum of clinical and immunologic manifestations caused by biallelic mutations in the LRBA gene. [2][3][4][5][6] LRBA is ubiquitously expressed and involved in signal transduction, vesicular trafficking, autophagy, and apoptosis; abolished expression may impair key processes related to immunity. 1,7,8 LRBA normally prevents cytotoxic T-lymphocyte protein-4 (CTLA4) from lysosomal degradation by bringing it back to the cell surface; its absence leads to decreased CTLA4 expression.…”

“…9 The resulting regulatory T (Treg)-cell defect causes immune dysregulation and autoimmunity, the symptoms of which partially resemble those of CTLA4 insufficiency (see Fig E1 in this article's Online Repository at www.jacionline.org). 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.…”

Chronic eyelid oedema and lacrimal gland swelling: Lets dig deeper!

“…LPS‐responsive beige‐like anchor protein (LRBA) deficiency was first described in 2012 as an autosomal recessive disorder caused by biallelic mutations in the LRBA gene that abolish LRBA protein expression. This disease impairs normal regulation of the immune system and results in lymphoproliferation, autoimmunity, hypogammaglobulinaemia and recurrent infections . Variable immunologic findings include deficiency of CD4+ T regulatory cells, decreased B‐cells and hypogammaglobulinaemia.…”

Whitish cystic lesions over the scrotum and penis

“…This disease impairs normal regulation of the immune system and results in lymphoproliferation, autoimmunity, hypogammaglobulinaemia and recurrent infections. 1 Variable immunologic findings include deficiency of CD4+ T regulatory cells, decreased B-cells and hypogammaglobulinaemia. Our index patient presented with immunodeficiency in form of recurrent sinusitis/EBV infection and immune dysregulation in the form of lymphoproliferation and cytopaenias.…”