Successful treatment by double-filtration plasmapheresis of a patient with bullous pemphigoid: effects in vivo on transcripts of several genes for chemokines and cytokines in peripheral blood mononuclear cells

Abstract

The involvement of various cytokines and chemokines has been reported in the pathogenesis of bullous pemphigoid (BP). Double-filtration plasmapheresis (DFPP) is an effective treatment for BP but the mechanism of action remains unclear. Using semiquantitative reverse transcription-polymerase chain reaction, we examined levels of transcripts for various cytokines and chemokines in freshly isolated peripheral blood mononuclear cells in a patient with BP before and after DFPP treatment. DFPP was performed four times. Relative levels of transcripts for interleukin (IL)-8, macrophage inflammatory protein (MIP)-1alpha and IL-5, and the ratio of relative levels of transcripts for IL-4 and interferon (IFN)-gamma, were higher, before treatment, than in healthy controls, and decreased when the extent of the lesions was reduced. Relative levels of transcripts for tumour necrosis factor (TNF)-alpha and IL-4 also decreased with regression of lesions, although they were similar to or lower than the corresponding levels in healthy individuals. When eruptions recurred, relative levels of transcripts for IL-8, MIP-1alpha, RANTES (regulated upon activation normal T cell expressed and secreted), IL-2, IFN-gamma and TNF-alpha were very much higher than those prior to the recurrence, while relative levels of mRNAs for IL-4 and IL-5 did not increase. Relative levels of transcripts for IL-8, MIP-1alpha, TNF-alpha and IL-2 were lower at the end of each individual DFPP and after the four treatments than at the beginning of treatment. Our observations suggest that cytokines and chemokines produced in mononuclear cells play important roles in the pathogenesis of BP and that regulation of their expression might be involved in the therapeutic effects of DFPP in BP.

A Controlled Study of Double Filtration Plasmapheresis in the Treatment of Active Rheumatoid Arthritis

“…DFPP can also reduce cytokines, as evidenced by lower levels of transcripts for interleukin-8, tumor necrosis factor-␣, and interleukin-2 at the end of each individual DFPP. 37 In agreement with this, DFPP lowered RF and CRP significantly in our study.…”

British Association of Dermatologists’ guidelines for the management of bullous pemphigoid 2012

“…29 Other small case series and anecdotal case reports have used different regimens of treatment with varying outcomes. [105][106][107] A child with BP and inflammatory bowel disease was treated with plasma exchange in combination with extracorporeal photochemotherapy that allowed reduction of immunosuppressive agents. 105 Immunoapheresis is a procedure by which immunoglobulins are removed from the circulation without the need to replace the plasma.…”

Successful Treatment of Severe Psoriatic Arthritis and Psoriasis with Double Filtration Plasmapheresis

“…In DFPP, a first filter was used to separate plasma from blood (plasma separator) and a second to filter larger molecules from the plasma (plasma fractionator). Disease activity of the patients with autoimmune diseases could be controlled completely following the rapid depletion of specific disease-associated plasma factors [20][21][22][23][24][25][26][27].…”

“…A biologic agent could target only a single inflammatory mediator and may show unsatisfactory results [17,18]. Double filtration plasmapheresis selectively removes high-molecular-weight substances, such as immunoglobulins, autoantibodies, immune complexes, acute-phase reactant proteins and cytokines [9,[19][20][21]. Double filtration plasmapheresis (DFPP) was conducted by application of a doublefiltration technique with a membrane plasmapheresis apparatus (Plasauto iQ, Asahi Medical Co., Tokyo, Japan).…”