P84: COMBINED IMMUNODEFICIENCY DUE TO DEFICIENCY OF ACTINRELATED PROTEIN COMPLEX 1B (ARPC1B)

Abstract

A number of cytoskeletal defects arising from perturbations in actin polymerisation and resulting in combined primary immunodeficiency (PID) have been described. Defects include Wiskott Aldrich Syndrome (WAS), WAS Interacting Protein (WIP) and Dedicator of Cytokinesis 8 (DOCK-8) deficiencies. A newly reported cytoskeletal defect is Actin-related Protein Complex 1B (ARPC1B) deficiency. Here we report the first Australian, youngest yet diagnosed, and 5th only reported case of ARPC1B deficiency. A female infant born to Nepalese parents presented with bloody diarrhoea and metabolic acidosis at 2 months of age. A diagnosis of cow’s milk enteritis was made and she was commenced on an elemental formula with resolution of the hematochezia and improvement in the diarrhoea. Subsequently she developed an eczematous rash which progressed to an erosive purpuric dermatitis with ulceration, and later took on a psoriasiform appearance. Skin biopsy showed a leucocytoclastic vasculitis. Her progress was complicated by cytomegalovirus infection, recurrent suppurative otitis media, twice by periorbital cellulitis, persistent oral candidiasis, urinary tract infection and failure to thrive. Investigations showed defective neutrophil chemotaxis and random migration, reduced Natural Killer cell cytotoxicity, decreased naïve T-cells, variable thrombocytopenia, eosinophilia, and raised IgA and IgE. Whole exome sequencing showed her to be homozygote for an exon 2 splice site mutation in ARPC1B (c.64+2T>A) which is predicted to cause loss of gene function. Western blot analysis showed low expression of the ARPC1B protein. ARPC1B is a regulatory subunit of the actin-related protein 2/3 complex critical for F-actin polymerisation in haemopoetic cells. Deficiency of ARPC1B results in defective actin polymerisation and a combined immunodeficiency similar but distinct to WAS.