Case Report: Novel UNC93B1 variant causes rheumatoid arthritis and interstitial pneumonia

TL;DR

A new mutation in the UNC93B1 gene is linked to rheumatoid arthritis and interstitial pneumonia in four patients, expanding the known clinical features of this genetic disorder.

Contribution

This case report identifies a novel UNC93B1 variant associated with rheumatoid arthritis and interstitial pneumonia, broadening the clinical spectrum of UNC93B1-related disease.

Findings

Four patients with a novel UNC93B1 c.1007G>A p.R336H variant presented with rheumatoid arthritis and interstitial pneumonia.

ISG score analysis showed overexpression of IFN-stimulated cytokine genes in one patient during active disease.

UNC93B1 mutations are now associated with 25 reported cases, including childhood-onset SLE and cutaneous lupus.

Abstract

UNC93B1 is a transmembrane protein essential for regulating toll-like receptors (TLRs). Pathogenic variants in human UNC93B1 have recently been described in a limited number of patients with childhood systemic lupus erythematosus and chilblain lupus.

Demographic data, medical history, and physical examination findings were obtained. Whole-exome sequencing and Sanger sequencing were performed. The interferon-stimulated gene (ISG) score was analyzed.

We report four patients with a novel UNC93B1 c.1007G>A p.R336H variant, including three presenting with juvenile arthritis or rheumatoid arthritis, and one with a predominant phenotype of ITP. In addition to arthritis, these patients presented with interstitial pneumonia as the dominant feature. ISG expression analysis during active disease revealed overexpression of IFN-stimulated cytokine genes and an elevated ISG score in P4. To date, 25 cases with UNC93B1 pathogenic mutations have been reported, including 13 with childhood-onset systemic lupus erythematosus (SLE) and 12 with cutaneous lupus. Management of these patients has varied based on clinical manifestations.

UNC93B1-mutation-associated disease should be considered in the context of early-onset autoimmune disease, especially childhood-onset SLE, juvenile arthritis, and rheumatoid arthritis. Pulmonary involvement should also be monitored in these patients.

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