B-Cell Signatures May Help Distinguish Cutaneous Lupus Erythematosus Subtypes in Patients With and Without SLE

Cutaneous lupus erythematosus (CLE) subtypes exhibit unique B-cell signatures in the absence of underlying systemic lupus erythematosus (SLE), according to study results published in Frontiers in Immunology.

Histologically, distinct subtypes of CLE include acute cutaneous lupus erythematosus (ACLE), subacute cutaneous lupus erythematosus (SCLE), and chronic cutaneous lupus erythematosus (CCLE), with discoid lupus erythematosus (DLE) being the most common subtype. Despite having consistent cellular and molecular patterns in patients with CLE with or without SLE, the shared and distinct molecular signatures of these subtypes are still not well understood.

In the current study, researchers aimed to investigate the differences in cellular and molecular patterns across CLE subtypes and the association between cutaneous lesion immune signatures and the presence of systemic lupus disease.

The study included 2 cohorts from the University of Michigan Pathology Database — the discovery cohort included gene expression profiles from 90 skin biopsies (DLE, n=47; SCLE, n=43), along with 13 healthy control skin biopsies; and the validation cohort included 60 skin biopsies (DLE, n=20; SCLE, n=20; ACLE, n=20) and 4 healthy control skin biopsies. Researchers examined the gene expression profile in skin biopsies in both the discovery and validation cohort. They also performed a weighted gene coexpression network analysis on 20,410 genes from the discovery cohort to examine gene expression patterns across all samples.  

Results of the study reported a unique skin immunoglobulin gene signature and higher skin B cell numbers for DLE lesions compared with SCLE and ACLE lesions. Overall, a higher skin B-cell signature was observed in DLE lesions compared with ACLE or SCLE lesions. More specifically, in both the discovery and validation cohorts, significantly higher gene expression signatures for B cells (P =.0001 and P <.0001, respectively), naive B cells (P =.0011 and P <.0001, respectively), and memory B cells (P <.0001 and P =.0001, respectively) were observed in skin lesions from patients with DLE compared with SCLE. Gene expression signatures of B cells, naive B cells, and memory B cells were significantly lower in ACLE skin lesions compared with DLE lesions (P =.0025, P =.0007, and P =.0070, respectively). No significant differences were observed between ACLE and SCLE lesions.

The CLE lesions from patients without SLE exhibited significantly more B-cell-associated gene expression (P =.0003). In CLE subtypes, a significantly higher B-cell expression was observed in lesions from patients with isolated DLE compared with DLE with underlying SLE (P =.0008).

Study limitations included limited long-term follow-up and clinical data, and the absence of ACLE skin lesion samples in the discovery cohort.

Researchers concluded, “B cell function in skin may be an important link between cutaneous lupus and systemic disease activity.” They also added, “Further study into the role of B cells, the recruitment and differentiation in lesional skin, and the types of antibody-secreting cells present will further enhance our ability to diagnose and treat CLE.”

Reference

Abernathy-Close L, Lazar S, Stannard J, et al. B cell signatures distinguish cutaneous lupus erythematosus subtypes and the presence of systemic disease activity. Front Immunol. Published  November 19, 2021. doi:10.3389/fimmu.2021.775353