IL-1β and IL-17 in cutaneous lupus erythematous skin biopsies: could immunohistochemicals indicate a tendency towards systemic involvement?

Background: Only a fraction of patients with cutaneous lupus erythematosus (CLE) will eventually progress toward systemic disease (SLE).

Objective: To find inflammatory biomarkers which could predict the progression of cutaneous lupus erythematosus (CLE) into systemic lupus erythematosus (SLE) using immunohistochemical (IHC) assays.

Methods: Immunohistochemical markers for cytotoxic, inflammatory, and anti-inflammatory responses and morphometric methods were applied to routine paraffin sections of skin biopsies, taken from lesions of 59 patients with discoid lupus, subacute lupus, and lupus tumidus. For the diagnosis of SLE, patients were classified by both the American College of Rheumatology (ACR-82) and the Systemic Lupus International Collaborating Clinics (SLICC-12) systems.

Results: Skin samples from CLE/SLE+patients presented higher expression of IL-1β (ARC-82: p=0.024; SLICC-12: p=0.0143) and a significantly higher number of cells marked with granzyme B and perforin (ARC: p=0.0097; SLICC-12: p=0.0148). Biopsies from CLE/SLE- individuals had higher expression of IL-17 (ARC-82: p=0.0003; SLICC-12: p=0.0351) and presented a positive correlation between the density of granzyme A+and FoxP3+ cells (ARC-82: p=0.0257; SLICC-12: p=0.0285) and CD8+ cells (ARC-82: p=0.0075; SLICC-12: p=0.0102), as well as between granulysin-positive and CD8+ cells (ARC-82: p=0.0024; SLICC-12: p=0.0116).

Study Limitations: Patients were evaluated at a specific point in their evolution and according to the presence or not of systemic disease. The authors cannot predict how many more, from each group, would have evolved towards SLE in the following years.

Conclusions: In this cohort, immunohistochemical findings suggested that patients with a tendency to systemic disease will show strong reactivity for IL-1β, while those with purely cutaneous involvement will tend to express IL-17 more intensely.