# 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.

## Key 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.