Loss of C9orf72 function leads to autoimmunity

A widely held view for the etiology of autoimmune diseases is that environmental factors combined with a proper genetic background can cause the disease. Rare monogenic diseases with autoimmune manifestations combined with new technologies, such as whole exon genomic sequencing, has unearthed fascinating mechanisms of autoimmune diseases. One such an example is the coatomer subunit alpha (COPA) syndrome which is caused by functionally defective variants of the COPA gene. COPA variants impair the retrograde transport of proteins from Golgi to endoplasmic reticulum (ER), increase ER stress and defective autophagy and lead to Th17 induction and expansion (1). COPA syndrome is manifested with interstitial lung disease, lung hemorrhages, arthritis, many autoantibodies, including antinuclear antibodies (ANA), anti-neutrophil cytoplasmic antibodies (ANCA), and rheumatoid factor (RF), Th17 immune response, and, in lung biopsies, germinal center formation (1).