Evaluation of the effectiveness of combined therapy with intravenous immunoglobulin and plasmapheresis in patients with steroid-resistant form of pemphigus based on the cytokine and chemokine profiles assessment

BACKGROUND: Pemphigus is a serious life-threatening disease characterized by the formation of IgG autoantibodies against the cell membranes, leading to the formation of intraepidermal blisters. AIM: To evaluate the effectiveness of combined therapy with intravenous immunoglobulin and plasma exchange for steroid-resistant patients with pemphigus based on the cytokine, chemokine and granulysin profiles investigation. MATERIALS AND METHODS: The group of patients receiving systemic glucocorticoid monotherapy (Group 1; control group) consisted of 26 patients with pemphigus vulgaris. The group of steroid-resistant patients (Group 2; main group) who received combined therapy with systemic glucocorticoid, intravenous immunoglobulin (IVIg), and plasmapheresis included 15 people. The presence of steroid resistance was assessed by Murrell consensus (2008). All pemphigus patients received the initial dose of systemic glucocorticoids of 80–100 mg/day with subsequent slow tapering, according to guidelines. The treatment protocol for combined therapy included four sessions of discrete plasma exchange per week every other day. Immediately after completion of the plasma exchange cycle, IVIg was added to the ongoing treatment, with a total dose of 2 g/kg per cycle. The levels of IL-4, IL-10, IL-15, TNF-α, chemokines CXCL8, CCL11, and granulysin were assessed via ELISA method. RESULTS: We observed some discrepancies in cytokine profiles in both groups of patients. In patients who received combined therapy, there was a statistically significant decrease in the levels of IL-4, IL-15, TNF-α compared to those in patients on systemic glucocorticoid monotherapy ― IL-4, IL-15 TNF-α (p 0.01). Notably, that the level of CCL11 in serum of steroid-resistant patients before the IVIg therapy was significantly higher (Me=51 pg/ml) compared to systemic glucocorticoid monotherapy group (Me=10 pg/ml; p 0.01). The level of granulysin after the treatment with IVIg and plasma exchange in group 2 was also significantly lower (Me=0 ng/ml) compared to the group of control (Me=2700 ng/ml respectively; p 0.01). CONCLUSION: We found a trend towards higher serum levels of IL-4, IL-15, and CCL11 in steroid-resistant pemphigus patients who received combined therapy with IVIg and plasma exchange compared to the control group. Moreover, these cytokines can be considered as the potential biomarkers for refractory disease course, and might be used as therapeutic targets in the future. It should be also noted that the prolonged remission of patients receiving combined therapy with systemic glucocorticoid, IVIg, and plasma exchange, was on average two years.