Adsorptive depletion of CD14(+) CD16(+) proinflammatory monocyte phenotype in patients with generalized pustular psoriasis: clinical efficacy and effects on cytokines.
Generalized pustular psoriasis (GPP) is a subtype of psoriasis with strong association with activated neutrophils. Adsorptive granulocyte and monocyte apheresis (GMA) is an extracorporeal intervention for selective depletion of activated granulocytes and monocytes. However, the immunological mechanism(s) for the effect of GMA on patients is not fully defined yet. We investigated the effects of GMA on the ratio of CD14(+) CD16(+) proinflammatory monocytes/CD14(+) monocytes and cytokine/chemokine production by these leukocytes including CXCL8, CCL2, CCL3, CCL4, CCL5 and tumor necrosis factor (TNF)-α in five patients with active GPP. CD14(+) CD16(+) monocytes were significantly elevated in patients with active GPP, and GMA markedly reduced the CD14(+) CD16(+) /CD14(+) ratio together with improvement of patients’ clinical symptoms. The serum levels of CXCL8, CCL3 and CCL4 were increased in active GPP patients. Likewise, CCL2 production from monocytes was increased in active GPP patients. Further, CCL3 and CCL4 production from monocytes in active GPP patients were reduced after a course of GMA. Serum CCL5 level and the release of CCL5 from monocytes in active GPP were significantly reduced, but TNF-α level in active GPP was similar to controls. Based on these results, we believe that in addition to neutrophils, elevated CD14(+) CD16(+) proinflammatory monocytes are part of the immune pathology in GPP. Accordingly, selective depletion of CD14(+) CD16(+) monocytes by GMA should be therapeutic in this condition.
Therapeutic leukocytapheresis for inflammatory bowel disease
Abbi R.Saniabadi, HiroyukiHanai, KenFukunaga, KojiSawada, ChikakoShima, IngvarBjarnason, RobertLofberg, https://doi.org/10.1016/j.transci.2007.08.003
The inference that granulocytes and monocytes/macrophages (GM) are part of the immunopathogenesis of inflammatory bowel disease (IBD) and hence should be targets of therapy stems from observations of elevated, and activated GM in patients with IBD. The Adacolumn can selectively deplete GM by adsorption (GMA) and in patients with IBD. GMA has been associated with significant clinical efficacy together with sustained suppression of inflammatory cytokine profiles. Additionally, GMA depleted proinflammatory CD14+CD16+ monocytes and was followed by an increase in CD4+ T lymphocytes including the regulatory CD4+CD25high+Foxp3 phenotype. Hence, GMA could be a non-pharmacologic therapy for IBD with potential to spare steroids and other unsafe pharmacologic preparations.
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