B Cell Signatures Distinguish Cutaneous Lupus Erythematosus Subtypes and the Presence of Systemic Disease Activity

Abstract

Cutaneous lupus erythematosus (CLE) is a chronic inflammatory skin disease characterized by a diverse cadre of clinical presentations. CLE commonly occurs in patients with systemic lupus erythematosus (SLE), and CLE can also develop in the absence of systemic disease. Although CLE is a complex and heterogeneous disease, several studies have identified common signaling pathways, including those of type I interferons (IFNs), that play a key role in driving cutaneous inflammation across all CLE subsets. However, discriminating factors that drive different phenotypes of skin lesions remain to be determined. Thus, we sought to understand the skin-associated cellular and transcriptional differences in CLE subsets and how the different types of cutaneous inflammation relate to the presence of systemic lupus disease. In this study, we utilized two distinct cohorts comprising a total of 150 CLE lesional biopsies to compare discoid lupus erythematosus (DLE), subacute cutaneous lupus erythematosus (SCLE), and acute cutaneous lupus erythematosus (ACLE) in patients with and without associated SLE. Using an unbiased approach, we demonstrated a CLE subtype-dependent gradient of B cell enrichment in the skin, with DLE lesions harboring a more dominant skin B cell transcriptional signature and enrichment of B cells on immunostaining compared to ACLE and SCLE. Additionally, we observed a significant increase in B cell signatures in the lesional skin from patients with isolated CLE compared with similar lesions from patients with systemic lupus. This trend was driven primarily by differences in the DLE subgroup. Our work thus shows that skin-associated B cell responses distinguish CLE subtypes in patients with and without associated SLE, suggesting that B cell function in skin may be an important link between cutaneous lupus and systemic disease activity.

Current Concepts on Pathogenic Mechanisms and Histopathology in Cutaneous Lupus Erythematosus

“…This also supports the assumption of Ackerman, who considers the different CLE subtypes as manifestations of the same pathological process ( 9 ). Nevertheless, there is evidence that the individual subtypes differ pathophysiologically, for example, with respect to their cellular composition as recently shown for B cells ( 10 ). Not only the molecular differences leading to the different clinical presentations need to be better understood, but also the pathogenic mechanisms of CLE in general: the precise role of involved cell types, the impact of different cytokines described in the disease, and their interaction and regulation in a complex network need further exploration.…”

“…The inflammatory cell infiltrate in LE skin lesions varies in composition and distribution depending on the subtype ( 10 , 11 , 50 ). Lipsker has developed a classification of specific histologic findings in CLE based on the primarily affected anatomic structure of the skin ( 9 , 51 ).…”

“…However, this concept could not explain the occurrence of the disease in autoantibody-negative patients ( 57 ). Interestingly, some studies reveal a B-cell-rich lesional infiltrate and a strong B cell associated gene signature (e.g., genes encoding B cell activator proteins such as BAFF as well as BAFF receptors) particularly in CLE subtypes lacking autoantibodies such as CDLE ( 10 , 46 ). Keratinocytes can produce large amounts of BAFF and thus can possibly interact with lesional lymphocytes expressing BAFF receptor ( 46 , 58 ).…”

Current concepts of photosensitivity in cutaneous lupus erythematosus

“…However, the extent to which B cells are directly involved in mechanisms of photosensitivity of lupus patients is poorly understood. Different B cell signatures have been detected in different subtypes of CLE, and it remains intriguing to what extent UV induces or influences this signature ( 110 ). Mast cells represent another component of the cutaneous immune system, and their function is particularly important in IgE-mediated diseases ( 111 ).…”

Efficacy and safety of topical nicotinamide in treatment of discoid lupus erythematosus

“…If you have SLE, you may be at risk for developing this condition. [1] According to the Düsseldorf categorization, there are four primary forms of CLE at the moment [2,3]: This condition is known as acute cutaneous lupus erythematosus (ACLE), and it is caused by lupus erythematosus (Lupus). Butterflies or "malar" rashes may be found in both localized and generalized forms (symmetrical widespread maculopapular rash, often including palms and soles).…”