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Journal of Clinical and
Basic Psychosomatics Proteomic analysis of mind-body psychotherapy in psoriasis
4.2. Comparative analysis of exosomal proteome in indicating immune system was recovering after MMIP. It
psoriasis patients before and after MMIP is known that hypogammaglobulinemia is a comorbidity
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Further, the expression levels of 16 proteins were altered of psoriasis, though the causative link remains unknown.
significantly before and after the therapy in psoriasis Intravenous immunoglobulin has been shown to exert a
patients. Among them, XP32 decreased after treatment, and therapeutic effect on a patient with psoriasis associated with
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it has been reported that XP32 is differentially expressed in hypogammaglobulinemia. The action of Ig on psoriasis is
non-lesional and lesional skin compared to healthy skin diverse, suggesting that it may be a double-edged sword.
and may contribute to maintaining the non-lesional state. In addition, the inflammatory markers such as ELAF
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DCD, which is a natural antibacterial peptide released by and PEBP1 were significantly elevated in patients with
sweat glands and is usually transported to the epidermal psoriasis and decreased after the therapy. Recently,
surface by sweat, also reduces in level after therapy. It has PEBP1 has been reported as one of the ferroptosis-related
been confirmed that DCD-derived polypeptide (86-103) genes that are altered in psoriasis. The ligand of PEPB1,
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could directly stimulate mast cells, trigger cytokine release phosphatidylethanolamine, is captured by CD1 proteins
in vitro, and cause a skin inflammatory response in wild- on autoreactive human T-cells, which are involved in
type mice, indicating its role in the onset and progression psoriasis. The metabolism of phospholipids in psoriasis
of psoriasis. 48 also warrants investigation. 57
KEGG pathway analysis showed that three pathways 4.3. Elafin in psoriasis patients and after MMIP
are involved in the recovery from psoriasis (Figure 3C).
Involvement of exosomal proteins such as ACTA2 and ELAF, also named PI3 or skin-derived antileucoproteinase,
VASP, as shown in the analysis results, could be by the is an elastase inhibitor produced by keratinocytes and
exosomal proteins being the source of tested specimens. initially purified from the skin of patients with psoriasis
More meticulous study about the roles of these exosomal in the 1990s. 58,59 It was reported that inflammatory
proteins in psoriasis development should be carried out. mediators (interleukin-1β or tumor necrosis factor-
PPI analysis illustrated the interaction of the three KEGG alpha) secreted by dermal neutrophils stimulate elafin
pathways. The decrease of ACTA2 and COF1 is linked. secretion and may be involved in the overexpression of
Cofilin binds to actin, induces a twist in the filament, ELAF in keratinocytes to protect the epidermis from
and critically contributes to phagocytosis. The linked degradation caused by dermal neutrophil infiltration.
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protein VASP may play a role in the phosphorylation and The previous studies have shown that ELAF responds
polymerization of actin. It was found that a decrease in to cyclosporin A and traditional Chinese Medicine.
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21
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these proteins compared to before the therapy was involved These prior results align with our finding that serum
in the recovery from psoriasis. In contrast, MYL6 and CAP1 ELAF became higher in psoriasis patients and decreased
increased after recovery. Phosphorylated MYL6 promotes significantly after the MMIP, suggesting that this form of
actin assembly and contraction, while dephosphorylated therapy can reduce inflammation of neutrophil infiltration
MYL6 inhibits them. Overexpression of CAP1 has been in psoriasis. Therefore, ELAF is one of the therapeutic
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shown to decrease the level of phosphorylated cofilin, markers of MMIP in the context of psoriasis. Furthermore,
indicating that CAP1 facilitated actin depolymerization. our proteomics analysis also revealed that the neutrophil
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The above-mentioned findings indicate that the reduction KLK6 that was elevated in psoriasis patients, significantly
in phagocytosis/antibody-dependent cellular cytotoxicity decreased following the MMIP. These findings demonstrate
(ADCC) is associated with improvements in psoriasis. the effectiveness of MMIP at molecular level, unveiled by
The ADCC-mediated Fc receptor is known to be exosome proteomics analysis.
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involved in psoriasis. The low Ig levels in psoriasis, as Furthermore, skin proteomes from three out of five
shown in Table 2, may be related to immune deficiency and/ patients showed that ELAF was significantly decreased
or enhanced ADCC activity against self-antigens through after receiving the therapy (unpublished data). Exosomes
Fc receptors. Alternatively, the increase of Ig after therapy act as carriers transferring proteins from skin to blood
(Q0ZCH6) also suggests the recovery of immune status and/ or vice verse, contributing to pathogenesis of psoriasis,
or the decrease of ADCC activity against self-antigens. and ELAF stands as a indicator of response to MMIP,
Notably, several Igs (A2NYU9, IGHG3, IGKV2-24, indicating that the extent of inflammation suppressed by
JCHAIN, IGHM, Q0ZCH6, and Q0ZCF9) were found MMIP in psoriasis or MMIP maintains the homeostasis
to be decreased in patients with psoriasis and apparently of skin barrier system. The previous studies also showed
elevated after the therapy in this study (Figure 2B), and that the levels of ELAF in blood and skin could reflect the
only Q0ZCH6 was significantly increased after the MMIP, severity of psoriasis. 60,61
Volume 2 Issue 3 (2024) 11 doi: 10.36922/jcbp.2381

