Presence of cutaneous interferon-a producing cells in patients with systemic lupus erythematosus

Abstract

Systemic lupus erythematosus (SLE) patients have increased levels of interferon-alfa (IFN-alpha) in the circulation but a reduced number of functionally intact natural IFN-alpha producing cells (IPC) in peripheral blood. In search for tissue localisation of activated IPC, we investigated skin biopsies from SLE patients for the occurrence of such cells. Eleven SLE patients with inflammatory skin lesions and six healthy controls were biopsied. An immunohistochemical technique (IH) and in situ hybridisation (ISH) were used to detect intracellular IFN-alpha protein and IFN-alpha mRNA, respectively. In all 11 biopsies from SLE lesions, a high number of IPC were detected by IH. In the nonlesional SLE biopsies we could also demonstrate IPC in 10/11 patients. In 6/11 SLE patients, IFN-alpha mRNA containing cells could be detected in the specimens. A low number of IPC were detected in 1/6 healthy controls by IH, but no ISH positive cells were seen. Our results demonstrate that SLE patients have active IPC in both dermal lesions and in noninflammatory skin. A recruitment of IPC from blood to peripheral tissues may explain the low number of circulating natural IPC in SLE patients. Because the type I IFN system is involved in the SLE disease process, these results are of interest for the understanding of the pathogenesis in SLE.

A possible mechanism for endogenous activation of the type I interferon system in myositis patients with anti–Jo‐1 or anti–Ro 52/anti–Ro 60 autoantibodies

“…The IFN␣ in the muscle tissue of these patients did not seem to be produced locally by BDCA-2-positive cells, since these were only seen as scattered cells in a few DM patients. The IFN␣ in DM patients may therefore be produced not only in muscles, but also in other organs, as previously observed (e.g., in the skin of SLE patients and in salivary glands of primary SS patients) (14,(31)(32)(33).…”

Analysis of gene expression profiles in human systemic lupus erythematosus using oligonucleotide microarray

“…25 Later, IFN-o was found in the sera of SLE, and it may also be a major IFN species produced by peripheral blood cells in SLE patients. 19,20,[26][27][28] In naturally occurring SLE, both circulating IFN-a and increased levels of IFN-a-inducible proteins, such as OAS1, OAS2, and OASL, have been reported. [19][20][21] Because long-term IFN-a therapy of patients with nonautoimmune disorders can induce antinuclear antibodies, antibodies to native DNA and also Fold-change Figure 2 Verification of microarray quantification.…”

The type I interferon system in systemic lupus erythematosus

“…Chemokines, such as CXCL10/CXCL12 and their corresponding receptors CXCR3/CXCR4, are important in this recruitment of NIPCs/PDCs to tissues (16). Interestingly, IFN␣ messenger RNA (mRNA) and proteinexpressing cells could be detected in biopsy specimens obtained from both lesional and apparently normal skin, indicating a general activation of NIPCs/PDCs in the setting of SLE (44). However, the lymphoid tissues may be the most important compartment for the NIPCs/ PDCs in SLE, where locally produced IFN␣ can directly act on cells in the immune system and promote the ongoing immune response.…”