In this study, we aimed to examine the relationship between the serum cytokine levels of patients with pemphigus vulgaris (PV) and the Pemphigus Disease Area Index (PDAI), along with the presence of anti‐desmoglein (Dsg) 1 antibody, anti‐Dsg3 antibody and co‐infection among patients with pemphigus vulgaris. This retrospective study included 62 PV patients and 59 healthy individuals who attended the Second Affiliated Hospital of Kunming Medical University from November 2014 to November 2022. The serum concentrations of cytokines and chemokines were assessed using the Luminex 200 System (a high‐throughput cytokine detection method). Additionally, anti‐Dsg1 and anti‐Dsg3 antibodies were determined through enzyme‐linked immunosorbent assay, while disease severity was evaluated using the PDAI scoring system. The PV group exhibited elevated levels of Th1 cytokines (such as interleukin (IL)‐1RA, IL‐1β, IL‐2, IL‐12p70, GM‐CSF, TNF‐α, IL‐18, IFN‐γ), Th2 cytokines (IL‐5, IL‐10, IL‐13) and Th17/Th22‐related cytokines (IL‐17A, IL‐22) compared to the healthy control group (p < 0.05). Conversely, the levels of chemokines (macrophage inflammatory protein‐1 alpha (MIP‐1α), stromal cell‐derived factor‐1 alpha (SDF‐1α), interferon‐inducible protein‐10 (IP‐10), Regulated on Activation in Normal T‐Cell Expressed And Secreted (RANTES), growth‐regulated on‐gene‐alpha (GRO‐α), MIP‐1β) and Th2 (IL‐31) were lower in the PV group compared to the healthy control group (p < 0.05). No significant differences were observed in other cytokines and chemokines (p > 0.05). Additionally, IL‐7, IFN‐γ, IL‐18 and GRO‐α showed positive correlations with PDAI, IL‐6 correlated positively with anti‐Dsg3 antibody levels, and IL‐12p70, IL‐18, and IFN‐γ correlated positively with anti‐Dsg1 antibody levels. Furthermore, IL‐15 exhibited a positive association with skin infections. PV patients have elevated levels of various cytokines and chemokines, and there are different degrees of elevation in cytokines and chemokines associated with the activation of various T cell subsets. PDAI and the Dsg1 antibody levels are mainly related to the Th1‐related cytokines.

2013-02-25·Endocrine connections3区 · 医学

Absence of some common organ-specific and non-organ-specific autoimmunity in autoimmune polyendocrinopathy candidiasis ectodermal dystrophy

3区 · 医学

ArticleOA

作者: Krohn, Kai ; Kluger, Nicolas ; Ranki, Annamari

BACKGROUND:

Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is a rare autosomal recessive disorder caused by mutations of the autoimmune regulator (AIRE) gene, whose loss of function leads to the escape of self-reactive T cells from the thymus and autoimmunity. APECED patients typically develop tissue-specific autoantibodies and anti-cytokine antibodies. Consequently, various endocrine and non-endocrine autoimmune disorders appear. However, only a certain number of autoimmune diseases develop, while some common autoimmune conditions have not been reported or are seen only anecdotally.

OBJECTIVE:

We investigated the clinical manifestations and occurrence of antinuclear antibodies (AN-Abs) and antibodies against extractable nuclear antigens, citrullinated peptide, and transglutaminase in 24 patients and against bullous pemphigoid antigen 180 and desmogleins 1 (Dsg1) and Dsg3 in 30 patients of a Finnish cohort of APECED patients.

RESULTS:

Despite the loss of central tolerance, the autoantibodies investigated were not overrepresented among the APECED patients. None of the patients had a history of autoimmune connective tissue disease, rheumatoid arthritis, celiac disease, or autoimmune cutaneous bullous disorders. Altogether, 25% (6/24) had low-titer (1:80) AN-Abs. Two patients had anti-BP180 antibodies and two others had anti-Dsg3 antibodies without any cutaneous or mucosal symptoms. No anti-citrullinated peptide and anti-transglutaminase reactivity was found.

CONCLUSIONS:

The mechanisms that drives tolerance to tissue autoantigens is not fully understood as even APECED patients, who are genetically prone to develop autoantibodies, are tolerant against some common autoantigens. The hypothesis that some of the anti-cytokine antibodies commonly found in APECED patients may be protective should be investigated in larger series.

2011-02-01·JOURNAL OF INVESTIGATIVE DERMATOLOGY

Aire-dependent thymic expression of desmoglein 3, the autoantigen in pemphigus vulgaris, and its role in T-cell tolerance.

Article

作者: Nagafuchi, Seiho ; Shimizu, Nobuyoshi ; Yamada, Taketo ; Nishifuji, Koji ; Wada, Naoko ; Kudoh, Jun ; Amagai, Masayuki ; Matsumoto, Mitsuru ; Peltonen, Leena

In the mechanism of thymus-induced central tolerance, the transcription factor Aire has been demonstrated to promote the expression of a wide range of peripheral organ-specific antigens (Ags) in the medullary thymic epithelial cells (mTECs), which serve as self-Ags in negative selection. We examined the expression of desmoglein 3 (Dsg3), the autoantigen in pemphigus vulgaris (PV), in mouse thymus and the involvement of Aire in tolerance to Dsg3. Immunofluorescence and in situ hybridization revealed Dsg3 in single cells or in clusters in ∼3% of mTECs near the cortico-medullary junction of the thymus in C57BL/6 mice. Dsg3-expressing mTECs also expressed some Ags of skin-unrelated peripheral organs simultaneously. In contrast, Dsg3-positive mTECs were not detected in the Aire(-/-) thymus. Adoptive transfer of splenocytes from Aire(-/-) mice immunized with Dsg3 did not induce anti-Dsg3 IgG production or PV phenotype in Rag2(-/-) recipient mice. However, Aire(-/-) CD4(+) T cells, but not Aire(+/+) CD4(+) T cells, induced low levels of anti-Dsg3 IgG production when transferred with Dsg3(-/-) B cells. These findings indicate that Aire has an important role in Dsg3 expression as well as in selection of T cells that help B cells to produce anti-Dsg3 IgG in thymus.

100 项与 DSG3 inhibitors(Chang Gung University) 相关的药物交易

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