TOPLINE:

In a prospective pilot study of patients with cutaneous or systemic lupus erythematosus (LE), SIGLEC-1 expression correlated with disease activity and type I interferon (IFN-I) gene scores and decreased with anifrolumab, a human monoclonal antibody blocking the IFN-I receptor.

METHODOLOGY:

• Researchers conducted a pilot study of 32 patients with LE (median age, 41 years; 88% female) at Brigham and Women’s Hospital from September 2022 to March 2024.
• There were 25 patients with systemic LE or cutaneous LE, four patients with cutaneous LE, and three patients with non-cutaneous systemic LE.
• The association of SIGLEC-1 expression with disease activity in patients with LE before or during IFN-I blockade was evaluated.
• Disease activity was assessed using the Clinical Systemic LE Disease Activity Index 2000 (cSLEDAI) and the Cutaneous LE Disease Area and Severity Index (CLASI) activity and damage scores. Median baseline cSLEDAI, CLASI-Activity, and CLASI-Damage scores were 4, 17, and 11, respectively.
• SIGLEC-1 expression on CD14-positive monocytes was measured by flow cytometry on fresh whole blood samples, with the IFN-I 21-gene score evaluated in seven patients using single-cell RNA sequencing.

TAKEAWAY:

• Systemic and cutaneous disease activity scores declined with anifrolumab treatment (P < .001 for both), whereas CLASI-Damage remained stable.
• Among 18 patients with blood samples, baseline SIGLEC-1 expression strongly correlated with CLASI-Activity (P = .002), CLASI-Damage (P = .02), and cSLEDAI scores (P = .03).
• SIGLEC-1 levels demonstrated a significant correlation with the IFN-I gene score (P = .003), and both declined following anifrolumab therapy.
• Two patients exhibited persistent or increased SIGLEC-1 expression despite complete treatment adherence and skin improvement, coinciding with refractory or relapsing nonskin manifestations.

IN PRACTICE:

“SIGLEC-1 shows promise as a real-time biomarker of IFN-I activity, which may guide use of IFN-I-targeted therapies,” the authors of the study wrote. “To our knowledge, SIGLEC-1 measurement is not yet routinely available in commercial diagnostic laboratories,” they noted, but “SI-GLEC-1 can be readily assessed by flow cytometry, a tool widely available globally.”

SOURCE:

The study was led by Alice Horisberger, MD, Brigham and Women’s Hospital, Harvard Medical School, Boston. It was published online in a letter on February 11 in JAMA Dermatology.

LIMITATIONS:

This was a single-center study, had a small sample size and had a predominance of skin-predominant LE cases in the cohort. Additionally, the SIGLEC-1 measurement was not widely available in commercial diagnostic laboratories at the time of the study.

DISCLOSURES:

The study was funded in part by the National Institutes of Health (NIH), the Burroughs Wellcome Fund Career Award in Medical Sciences, and the Swiss National Foundation Early Postdoc Mobility. One author reported receiving grants from NIH and the Swiss National Science Foundation during the conduct of the study. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.