BACKGROUND

Although the contribution of aberrant CD4 T cell signaling to systemic lupus erythematosus (SLE) is well established, its role in cutaneous lupus erythematosus (CLE) skin is largely unknown. Because the rate of systemic manifestations varies in each subtype, resident memory CD4 T cells in lesions that are responsible for only skin-associated tissue responses may vary in each subtype. However, the role of CD4 tissue-resident memory T (CD4 Trm) cells in each CLE subtype remains unclear.

OBJECTIVES

To analyze and compare CD4 Trm cells and absent in melanoma 2 (AIM2) identified by smart RNA sequencing (Smart-seq) in CD4 Trm cells from patients with acute CLE (ACLE), subacute CLE (SCLE), and localized discoid lupus erythematosus (localized DLE) lesions.

METHODS

We performed Smart-seq to investigate differences in dermal CD4 Trm cells between patients with ACLE and normal controls (NCs). Multicolor immunohistochemistry was utilized to measure the levels of AIM2 in CD4 Trm cells present in the skin of 134 clinical patients, which included patients with localized DLE (n = 19), ACLE (n = 19), SCLE (n = 16), psoriasis (n = 12), rosacea (n = 17), lichen planus (n = 18), and annular granuloma (n = 15), as well as NCs (n = 18).

RESULTS

The Smart-seq data showed higher AIM2 expression in skin CD4 Trm cells from ACLE lesions than NCs (fold change >10, adjusted P < 0.05). AIM2 expression in CD4 Trm cells did not vary according to age or sex. AIM2 expression in CD4 Trm cells was significantly lower in patients with ACLE (6.38 ± 5.22) than localized DLE (179.41 ± 160.98, P < 0.0001) and SCLE (63.43 ± 62.27, P < 0.05). In an overall comparison of ACLE with localized DLE and SCLE, the receiver operating characteristic curve for AIM2 expression in CD4 Trm cells had a sensitivity of 100.00% and a specificity of 82.86% at a cutoff value of 18.26. In a comparison of ACLE with localized DLE, the sensitivity was 89.47%, and the specificity was 100.00% at a cutoff value of 12.26. In a comparison of ACLE with SCLE, the sensitivity was 100.00%, and the specificity was 75.00% at a cutoff value of 18.26.

CONCLUSIONS

The number of CD4 Trm cells is increased in lesions of SCLE and localized DLE compared to ACLE, suggesting that CD4 Trm cells may have a more crucial role in persistent lesions of SCLE and localized DLE. In addition, AIM2 expression in CD4 Trm cells discriminates patients with ACLE from those with localized DLE and SCLE.