COPA Syndrome from Diagnosis to Treatment: A Clinician's Guide

Abstract

COPA syndrome is a recently described autosomal dominant inborn error of immunity characterized by high titer autoantibodies and interstitial lung disease, with many individuals also having arthritis and nephritis. Onset is usually in early childhood, with unique disease features including alveolar hemorrhage, which can be insidious, pulmonary cyst formation, and progressive pulmonary fibrosis in nonspecific interstitial pneumonia or lymphocytic interstitial pneumonia patterns. This review explores the clinical presentation, genetics, molecular mechanisms, organ manifestations, and treatment approaches for COPA syndrome, and presents a diagnostic framework of suggested indications for patient testing.

Keywords: Alveolar hemorrhage; Arthritis; Autoantibody; COPA syndrome; Child; Infant; Interstitial lung disease; Nephritis.

Fig. 1.

Structure of COPA locus, exons are marked in boxes shaded to correspond with protein motifs. Detail of WD regions containing COPA mutations highlighted. Validated mutations (K230 N, R233H, E241 K, V242 G, D243 G, D243 N) and variants from case report tightly cluster between amino acids 230 to 243, underlined and marked with asterisks. Arrows point to additional mutations from case reports describing patients with consistent phenotypic features (see Table 1 for full details). (Data from Quek et. al. in Cytogenetic and Genome Research, 1997.)