Characterization of B cells in lupus erythematosus skin biopsies in the context of different immune cell infiltration patterns

Abstract

Cutaneous lesions in lupus erythematosus (LE) subtypes are heterogenous. In line with the heterogeneity of the clinical presentation, the underlying lesional inflammation in LE skin samples is defined by different immune cell infiltrates. Pathophysiologically, lesional inflammation is driven by autoreactive cytotoxic T cells, targeting keratinocytes; plasmacytoid dendritic cells (pDCs), producing large amounts of interferon (IFN); and B cells, whose function in cutaneous LE is still unclear. This study aims to (a) classify inflammatory patterns with regard to the dominating cell type or cytokine expression and (b) investigating the specific role of B cells in LE skin lesions. Therefore, the immunohistological expression of inflammatory surrogates (CD20, CD123, MXA) in skin samples of n = 119 LE (subtypes: subacute cutaneous LE, chronic discoid LE, chilblain LE, LE tumidus, other LE) and n = 17 patients with inflammatory skin diseases (atopic dermatitis, psoriasis) were assessed. Samples were classified with regard to inflammatory groups. In addition multiplex-immunohistochemical analyses of n = 17 LE skin samples focusing on lesional B cells were conducted. In this study, we show that cutaneous lesions present with eight different inflammatory groups dominated by B cells, pDCs, a strong IFN expression, or overlapping patterns. Altogether, LE subtypes show heterogenous infiltration regardless of LE subtype, certain subtypes display a preference for infiltration groups. Furthermore, lesional B cells either form diffuse infiltrates or pseudofollicular structures, wherein they show antigen-presenting and T cell-activating properties. Altogether, in the light of emerging targeted therapeutic options, we suggest histological assessment in regard to B-cell or pDC preponderance to allow tailored treatment decisions.

Cutaneous Lupus Erythematosus: An Update on Pathogenesis and Future Therapeutic Directions

“…PDC infiltrates are observed in a great proportion of skin biopsies and can form clusters in CLE skin lesions [ 38 , 40 ]; however, not all skin lesions harbor a pDC infiltrate [ 41 ]. Recently, single-cell ribonucleic acid (RNA) and spatial RNA sequencing has shown that even healthy-appearing skin of CLE patients contains a type I IFN-rich environment and that CD16+ DCs undergo IFN priming in the skin, leading to proinflammatory subtypes [ 42 ].…”

“…Recently, the understanding of the pathophysiological role of B cells in LE has shifted, since strong B-cell signatures and lesional B-cell infiltrates have been described in patients with autoantibody-negative CLE [ 41 , 78 ]. Beside antibody production, B cells can contribute to the autoimmune reaction by different mechanisms.…”

“…Beside antibody production, B cells can contribute to the autoimmune reaction by different mechanisms. For example, emerging evidence points towards an antigen-presenting, T-cell activating function of B cells [ 41 ]. Lesional B-cell infiltration varies among LE subtypes [ 41 , 79 ].…”

“…For example, emerging evidence points towards an antigen-presenting, T-cell activating function of B cells [ 41 ]. Lesional B-cell infiltration varies among LE subtypes [ 41 , 79 ]. B cells can form clusters and arrange in lymphoid-like structures in the skin, called tertiary lymphoid organs/structures (TLO).…”

“…In different subtypes of CLE, the formation of dense B-cell clusters or TLOs has been described, e.g. in LE profundus or CDLE [ 41 , 80 ]. TLOs are highly organized structures containing T and B cells, contributing to autoimmunity [ 81 ], and have been described in detail in lupus nephritis [ 82 , 83 ].…”