JAK inhibition may prevent drug hypersensitivity reactions
Xiangmei Hua, Pranali N. Shah, Gustavo A. Velasquez, Lillian Sidky, George A. Romar, Lydia W. Boer, Natalie Hickerson, Tracy Qiying Cui, Federico Repetto, Abigail Waldman, Marilyn G. Liang, J. Paul Marcoux, MacLean Sellars, Victor Barrera, Birgitta A.R. Schmidt, Arash Mostaghimi, Ruth K. Foreman, Christine G. Lian, Sherrie J. Divito
Xiangmei Hua, Pranali N. Shah, Gustavo A. Velasquez, Lillian Sidky, George A. Romar, Lydia W. Boer, Natalie Hickerson, Tracy Qiying Cui, Federico Repetto, Abigail Waldman, Marilyn G. Liang, J. Paul Marcoux, MacLean Sellars, Victor Barrera, Birgitta A.R. Schmidt, Arash Mostaghimi, Ruth K. Foreman, Christine G. Lian, Sherrie J. Divito
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Research Letter Dermatology Immunology

JAK inhibition may prevent drug hypersensitivity reactions

Abstract

Authors

Xiangmei Hua, Pranali N. Shah, Gustavo A. Velasquez, Lillian Sidky, George A. Romar, Lydia W. Boer, Natalie Hickerson, Tracy Qiying Cui, Federico Repetto, Abigail Waldman, Marilyn G. Liang, J. Paul Marcoux, MacLean Sellars, Victor Barrera, Birgitta A.R. Schmidt, Arash Mostaghimi, Ruth K. Foreman, Christine G. Lian, Sherrie J. Divito

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Figure 1

JAKi prophylaxis may prevent DHR in mice and humans.

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JAKi prophylaxis may prevent DHR in mice and humans. (A and B) Represent...
(A and B) Representative (A) gross and (B) histologic ear images of HLA-B*57:01pos and HLA-B*57:01neg mice prophylaxed with tofacitinib (tof), ruxolitinib (rux), or vehicle (veh) and then treated with abacavir. (C) Ear thickness measurement. (D) Total number of MHCII+CD11b+CD11chi myeloid DCs per ear and Δ mean fluorescence intensity (MFI) of CD86 on ear DC by flow cytometry. (E) Total number of CD44hiCD62LloCD8+ effector T cells in ear skin by flow cytometry. Pooled results are shown from 2 independent experiments; n ≥ 5 per group. (C) Two-way ANOVA with Bonferroni correction; (D and E) 1-tailed unpaired Welch’s t test; *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001; #P < 0.05; ##P < 0.01; ###P < 0.001. (F) Patient clinical course schematic. (G) Representative clinical and histology images. Clinical exam showed diffuse maculopapular exanthem with subtle targetoid patches with central duskiness observed in areas of skin pain. Skin biopsy revealed spongiosis and vacuaolar interface dermatitis with perivascular lymphocytic infiltrate and eosinophils. (H) Representative IHC images (antigenic target, purple; counterstain, green). Scale bars: 100 μm.