Psoriasis is one of the most common chronic inflammatory skin diseases, affecting ~2% of the population. The lack of characterization of the pathogenesis of psoriasis has hindered efficient clinical treatment of the disease. In our study, we observed that expression of complement component 5a receptor 1(C5aR1) was significantly increased in skin lesions of both imiquimod (IMQ) and IL23-induced psoriatic mice and patients with psoriasis. C5aR1 deficiency or treatment with C5a receptor 1 antagonist (C5aR1a) in mice significantly attenuated psoriasis-like skin lesions and expression of inflammatory cytokines and chemokines. Moreover, C5aR1 deficiency significantly decreased IMQ-induced infiltration of plasmacytoid dendritic cells (pDCs), monocytes and neutrophils in psoriatic skin lesions and functions of pDCs, evidenced by the remarkable reduction in the IMQ-induced production of interferon-α (IFN-α) and tumor necrosis factor α (TNF-α), and FMS-like tyrosine kinase 3 ligand (FLT3L)-dependent pDCs differentiation. Accordingly, in vitro treatment with recombinant C5a accelerated pDCs migration and the differentiation of bone marrow cells into pDCs. Furthermore, biopsies of psoriatic patients showed a dramatic increase of C5aR1 + pDCs infiltration in psoriatic skin lesions, compared to healthy subjects. Our results provide direct evidence that C5a/C5aR1 signaling plays a critical role in the pathogenesis of psoriasis. Inhibition of C5a/C5aR1 pathway is expected to be beneficial in the treatment of patients with psoriasis.

Rheumatoid arthritis (RA) is a relatively common autoimmune disease that is associated with progressive disability and systemic complications, with a relatively high socioeconomic burden. The treatment of RA has been revolutionized by the use of biological drugs, such as anti-tumor necrosis factor (TNF) agents. A wide spectrum of RA disease severity has been reported among patients with human immunodeficiency virus (HIV) infection. Yet, only a few cases using anti-TNF therapy have been described in this clinical population. Therefore, the aim of our case-based review was to describe the successful use of etanercept in a 38-year-old female patient with RA concomitant with HIV infection, who had been resistant to the first-line anti-rheumatic therapies. As per routine care guidelines, the patient was screened for hepatitis virus infection, latent tuberculosis, and other infectious conditions, prior to the initiation of etanercept treatment. CD4 cell count, HIV viral load, and adverse effects were closely monitored during the treatment. The HIV infection remained stable with etanercept treatment, without the need for anti-retrovirus agents. No adverse effects and serious infections were identified during the treatment. Therefore, anti-TNF therapy is a viable alternative for the treatment of RA in patients with HIV, who do not respond to conventional anti-rheumatic therapies. The relationship between TNF-α and HIV infection, as well as cautionary guidelines regarding the utilization of anti-TNF therapy in this clinical population, is discussed.

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