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Introduction What’s already known?

Analysis of anti-TNF-induced skin lesions reveals strong Th1 activation with some distinct immunological characteristics.

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Introduction What’s already known?

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  1. Analysis of anti-TNF-induced skin lesions reveals strong Th1 activation with some distinct immunological characteristics Elina Stoffel, Harald Maier, Elisabeth Riedl, Marie-Charlotte Brüggen, Bärbel Reininger, Michaela Schaschinger, Christine Bangert, EmmanuellaGuenova, Georg Stingl, Patrick M. Brunner British Journal of Dermatology. DOI: 10.111/bjd.16126

  2. Introduction What’s already known? • Psoriasiform and eczematous lesions are the most common skin adverse events of anti-TNF- treatment, and unopposed interferon/IFN- production by plasmacytoid dendritic cells has been suggested as an eliciting factor. • However, a comprehensive and comparative immune profile has not been performed so far. Seneschal J et al.: Br J Dermatol 2009;161:1081-8. Palucka AK et al.: ProcNatlAcadSci U S A 2005;102:3372-7. Collamer AN et al.: Semin Arthritis Rheum 2010;40:233-40.

  3. Methods • 19 patients on anti-TNF-α-treatment with new-onset scaly erythematous skin lesions were biopsied (17 with IBD, 2 with rheumatoid arthritis) • Biopsies were assessed by • Conventional histopathology • Quantitative RT-PCR • Multicolor immunofluorescence stainings using analyzed by TissueFAXS

  4. Results • On a histopathological level, biopsies could be assigned to four different reaction patterns

  5. Results • Using a psoriasis-eczema disease classifier,1 we found that psoriasiform and spongiotic (eczematous) anti-TNF lesions were distinct from conventional psoriasis or eczema. 1Quaranta M et al.: Sci Transl Med. 2014 Jul 9; 6(244): 244ra90

  6. Results • Using the same molecular classifier,1 scalp lesions were also neither consistent with psoriasis nor with eczema 1Quaranta M et al.: Sci Transl Med. 2014 Jul 9;6(244):244ra90

  7. Results • Despite upregulation of several different immune axes, including strong IL-17 responses, we found that anti-TNF lesions were uniformly characterized by a strong IFN-γinflammatory signature.

  8. Results • IFN-γwas most likely produced by CD3/CD4/Tbet-positive Th1 lymphocytes in psoriasiform and spongiotic anti-TNF lesions.

  9. Results • Scalp lesions showed several differences in cytokine expression compared to psoriasiform and spongiotic lesions

  10. Discussion What does this study add? • We could demonstrate that new-onset psoriasiform, eczematous and scalp anti-TNF-induced skin lesions show distinct immunological patterns with characteristic Th1/IFN-γ/IFN-α-associated inflammation and major differences from both conventional psoriasis and eczema.

  11. Conclusions • Results might help to guide future treatment strategies for chronic inflammatory diseases preventing these skin side effects.

  12. Call for correspondence • Why not join the debate on this article through our correspondence section? • Rapid responses should not exceed 350 words, four references and one figure • Further details can be found here

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