The role of T cells in cutaneous autoimmune disease

Chow, S. K.; Rizzo, Carina; Ravitskiy, Larisa; Sinha, Animesh A.

doi:10.1080/08916930500124429

Cited by 29 publications

(18 citation statements)

References 209 publications

(205 reference statements)

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“…IgA deficiency and autoimmunity 77 who have megaloblastic anemia and chronic diarrhoea, or gastrointestinal symptoms. Cutaneous autoimmune manifestations such as psoriasis, vitiligo, chronic urticaria, pemphigus vulgaris, and cutaneous lupus erythematosus may be observed in immunodeficient adults [28]. However, our IgAD patients did not have any cutaneous symptoms.…”

Section: Discussionmentioning

confidence: 96%

Increased percentages of autoantibodies in immunoglobulin A-deficient children do not correlate with clinical manifestations

et al. 2009

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IgA deficiency (IgAD) is frequently associated with autoimmune phenomena. The aim of this study is to evaluate the frequency of 22 different autoantibodies in 60 patients with IgAD and to examine the physical and other laboratory findings of the suspected cases for autoimmune diseases. The evaluated autoantibodies were Anti-nuclear antibody (ANA) profile (autoantibodies against RNP/Sm, SS-A, Ro-52, SS-B, Scl-70, Pm-Scl, Jo-1, centromere B, PCNA, dsDNA, nucleosomes, histones, ribozomal P-protein, AMA-M2), anti-cardiolipin IgG and IgM, anti-neutrophilic cytoplasmic antibodies (ANCA), rheumatoid factor (RF), anti-thyroglobulin (anti-T) and anti-thyroid microsomal antigen (anti-M) and direct cooms test. Forty-one healthy children were included as a control group. ANA titers < or = 1:80 were accepted as normal and titers > or = 1:80 are accepted as positive. In ANA screening, 14 patients showed positivity in different titres. Seven of them were equal to or below 1:80. The other seven patients (11.6%) had positive ANA titers (>1:160) whereas three of them had anti-dsDNA, anti-histon and anti-centromer antibodies. These patients did not have any clinical and laboratory signs of autoimmune diseases. ANA positivity was found higher in IgA deficient children (p < 0.05) compared to controls. RF and pANCA were found positive during follow-up of two different selective IgAD patients. IgG and IgM antibodies against cardiolipin, direct coombs, anti-T and anti-M tests were not found positive in any subjects. In conclusion, increased frequency of autoantibodies in IgAD patients may often be observed. However, the detection of autoantibodies do not show or predict whether this patient will develop an autoimmune disease.

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Section: Discussionmentioning

confidence: 96%

Increased percentages of autoantibodies in immunoglobulin A-deficient children do not correlate with clinical manifestations

et al. 2009

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“…For the cutaneous blistering disorders in which autoantibodies are known to produce direct end organ (skin) damage, such as pemphigus vulgaris, pemphigus foliaceous, and bullous pemphigoid, there is clear evidence for the role of antigen-specific T cells in mediating antibody production and, therefore, the disease process [88]. The association of a specific autoantibody and CTL responses with distinct disease phenotypes is observed in both autoimmune diseases and cancer.…”

Section: Humoral and Cytotoxic Immunity In Pamsmentioning

confidence: 98%

“…In autoimmune diseases in which pathogenicity is mediated by autoantibodies, T H 2 lymphocytes have a key role in the activation of B cells and the subsequent production of the autoantibody [88]. For the cutaneous blistering disorders in which autoantibodies are known to produce direct end organ (skin) damage, such as pemphigus vulgaris, pemphigus foliaceous, and bullous pemphigoid, there is clear evidence for the role of antigen-specific T cells in mediating antibody production and, therefore, the disease process [88].…”

Section: Humoral and Cytotoxic Immunity In Pamsmentioning

confidence: 99%

Paraneoplastic autoimmune multiorgan syndrome: Review of the literature and support for a cytotoxic role in pathogenesis

2006

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Paraneoplastic autoimmune multiorgan syndrome (PAMS), first described as paraneoplastic pemphigus in 1990, is an autoimmune blistering disease associated with neoplasia. Patients with this rare disorder have severe blistering and painful erosions of the oral cavity and various other cutaneous findings ranging from classic pemphigus vulgaris-like erosions to targetoid lesions resembling erythema multiforme and papular to more confluent lichenoid eruptions. This syndrome involves multiple organ systems, and its high rate of mortality often stems from constrictive bronchiolitis obliterans. The histologic findings are as diverse as the clinical presentation, often making diagnosis difficult initially. Immunodermatologic and serologic laboratory findings typically establish the diagnosis. These results can be confirmed with immunoprecipitation profiling of specific molecular weight protein markers. The proposed pathogenesis of PAMS continues to evolve, and recent reports implicate the involvement of cell-mediated, cytotoxic immunity, in addition to humoral autoantibodies. This review characterizes and summarizes the clinical, pathologic, and immunohistologic features of PAMS and outlines the possible role of cytotoxic T lymphocytes in the pathogenesis of this syndrome.

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“…In this study, we have shown that UR-1505, a new immunomodulator agent chemically related to salicylic acid, blocked T-cell activation, which might be a useful strategy for the treatment of autoimmune diseases, given the key role of T-cell activation in the onset of these diseases (Chow et al, 2005;Goudy and Tisch, 2005;Howard et al, 2005;Walter and Santamaría, 2005). It is important that the prevention of T-cell activation produced by UR-1505 was done in a lower range of concentrations (0.1 -0.3 mM) than those reported previously for acetylsalicylic acid (2-4 mM) (Paccani et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

UR-1505, a New Salicylate, Blocks T Cell Activation through Nuclear Factor of Activated T Cells

et al. 2007

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2-Hydroxy-4(-2,2,3,3,3-pentafluoropropoxy)-benzoic acid (UR-1505), a new molecule chemically related to salicylic acid, has immunomodulator properties and is currently under clinical development for treatment of atopic dermatitis. The present work describes the immunomodulatory profile of UR-1505. UR-1505 targets T cells, inhibiting their proliferation and cytokine production by blocking nuclear factor of activated T cells (NF-AT) DNA-binding activity. The effects of UR-1505 (100 -300 M) on T cell proliferation seems to be dependent on the stimulus, because UR-1505 inhibited CD3/CD28-induced Tcell proliferation, increased p27 KIP levels, and induced G 1 /S cell arrest but, interestingly, did not inhibit the Janus tyrosine kinase/signal transducer and activator of transcription-induced T-cell proliferation. These data suggest that UR-1505 acts by means of a specific mechanism inhibiting T cell activation depending on T cell receptor signaling pathway. Furthermore, the antiproliferative effects of UR-1505 are not a consequence of decreased cell viability. In addition to the inhibition of T-cell proliferation, UR-1505 decreased, in a dose-dependent manner, the production of interleukin (IL)-5 and interferon (IFN)-␥ in activated T cells, and this effect was produced at the transcriptional level. Because T-cell proliferation and cytokine production were regulated through NF-AT, we examined the effect of UR-1505 on this transcription factor. According to its effect on IL-5 and IFN-␥ mRNA expression, UR-1505 specifically inhibited NF-AT DNA binding without effect on nuclear factor-B and activator protein-1 activities. The effect of UR-1505 on NF-AT is not attributable to a blockade of nuclear import. In conclusion, UR-1505 is a new immunomodulator agent that specifically inhibits NF-AT activation. Because NF-AT regulates the transcription of most genes involved in lymphocyte activation, its selective inactivation results in both decreased T-cell proliferation and cytokine production.

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The role of T cells in cutaneous autoimmune disease

Cited by 29 publications

References 209 publications

Increased percentages of autoantibodies in immunoglobulin A-deficient children do not correlate with clinical manifestations

Increased percentages of autoantibodies in immunoglobulin A-deficient children do not correlate with clinical manifestations

Paraneoplastic autoimmune multiorgan syndrome: Review of the literature and support for a cytotoxic role in pathogenesis

UR-1505, a New Salicylate, Blocks T Cell Activation through Nuclear Factor of Activated T Cells

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