Background/Purpose: Cutaneous lupus erythematosus (CLE) is the cutaneous manifestation of SLE, affecting 85% of patients¹. CLE is subdivided into acute, subacute and chronic/discoid forms. Discoid lupus erythematosus (DLE) can present in the absence of SLE, but up to 28% of DLE subjects will progress to SLE². CLE lesions are characterized by interface dermatitis and a dermal perivascular immune infiltrate consisting largely of lymphocytes and histiocytes, with relatively large numbers of plasmacytoid dendritic cells (pDCs), with or without fibrosis. As robust producers of type I interferon, pDCs may play a central role in the pathogenesis of CLE lesions. To monitor the effect of therapeutic pDC-specific inhibition, we aimed to develop quantitative interlesional measures of immune infiltrate and Type I IFN pathway related proteins.

Methods: Patients with lesions consistent with a diagnosis of CLE and treated according to standard of care were recruited by the Perelman Center for Advanced Medicine at the University of Pennsylvania. Enrolled patients presented with subacute, chronic (other than discoid) or discoid forms of CLE with or without systemic lupus erythematosus as defined by ≥4 out of 11 classification criteria (n=10 subjects who met SLE criteria out of a total of n=19, mean CLASI = 14.21 (range=1-29). At baseline and week 12, 3-5 mm punch biopsies from active CLE lesions were collected and used for immunohistochemistry with anti-MxA (MX dynamin-like GTPase), CD45 (hematopoietic cells) and CD303 (BDCA-2) antibodies. Glass slides were examined, then digitized. Using custom-designed algorithms in Visiopharm (Denmark) software, percent areas were quantified as the portion of immunoreactive area / total tissue area for epidermis, papillary dermis and reticular dermis. R and p represent Pearson correlation and p-values.

Results: At baseline (n=19 subjects), CLASI correlated with relative area of epidermal (but not dermal) CD45 (r=0.72, p=0.0005) and MxA (r=0.61, p=0.0056). Also at baseline, relative area of CD303 correlated with MxA in all skin regions. Compared with papillary and reticular dermis, MxA was enriched in epidermis. In contrast, CD45+ and CD303+ cells were most plentiful in papillary and reticular dermis. Biopsies from the second visit (week 12) were available for 14 subjects. When all skin regions were combined, longitudinal change in CLASI correlated with change in CD45⁺ (r=0.59, p=0.0255) and MxA⁺ relative areas (r=0.61, p=0.0218).

Conclusion:

At a single time point and as indicators of longitudinal change, relative areas of MxA and CD45 are useful tissue-based biomarkers. They can be used to complement CLASI in the setting of a clinical trial. These findings warrant investigation of tissue-based quantification of CD45 and MxA for stratification of CLE patients and to augment biopsy evaluation in the diagnostic setting.

1. Rothfield, N., R.D. Sontheimer and M. Bernstein (2006). “Lupus erythematosus: systemic and cutaneous manifestations.” Clin Dermatol 24(5)
2. Chong, B. F., J. Song and N. J. Olsen (2012). “Determining risk factors for developing systemic lupus erythematosus in patients with discoid lupus erythematosus.” Br J Dermatol 166(1)

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/tissue-based-biomarkers-in-cutaneous-lupus-erythematosus-type-i-ifn-responsive-protein-mxa-and-a-marker-for-lymphocytic-inflammation-cd45-correlate-with-clasi-cross-sectionally-and-longitudinally/