New discoveries in the genetics and genomics of systemic juvenile idiopathic arthritis

Expert Rev Clin Immunol. 2024 May 2:1-12. doi: 10.1080/1744666X.2024.2345868. Online ahead of print.

Abstract

Introduction: Systemic juvenile idiopathic arthritis (sJIA) is a severe inflammatory condition with onset in childhood. It is sporadic, but elements of its stereotypical innate immune responses are likely genetically encoded by both common variants with small effect sizes and rare variants with larger effects.

Areas covered: Genomic investigations have defined the unique genetic architecture of sJIA. Identification of the class II HLA locus as the strongest sJIA risk factor for the first time brought attention to T lymphocytes and adaptive immune mechanisms in sJIA. The importance of the human leukocyte antigen (HLA) locus was reinforced by recognition that HLA-DRB1*15 alleles are strongly associated with development of drug reactions and sJIA-associated lung disease (sJIA-LD). At the IL1RN locus, genetic variation relates to both risk of sJIA and may also predict non-response to anakinra. Finally, rare genetic variants may have critical roles in disease complications, such as homozygous LACC1 mutations in families with an sJIA-like illness, and hemophagocytic lymphohistiocytosis (HLH) gene variants in some children with macrophage activation syndrome (MAS).

Expert opinion: Genetic and genomic analysis of sJIA holds great promise for both basic discovery of the course and complications of sJIA, and may help guide personalized medicine and therapeutic decision-making.

Keywords: Macrophage activation syndrome; genetics; genomics; lung disease; still’s disease.

Publication types

  • Review