Transcriptome profiling of refractory atopic keratoconjunctivitis by RNA sequencing

• Published in: Journal of allergy and clinical immunology 2019-04, Vol.143 (4), p.1610-1614.e6
• Main Authors: Matsuda, Akira, Asada, Yosuke, Suita, Naomasa, Iwamoto, Satoshi, Hirakata, Toshiaki, Yokoi, Norihiko, Ohkawa, Yasuyuki, Okada, Yukinori, Yokomizo, Takehiko, Ebihara, Nobuyuki
• Format: Article
• Language: English
• Subjects: Actin; Activation; Adaptive immunity; Adhesion; Adipogenesis; Adolescent; Aged; Apolipoprotein E; Apolipoprotein E4; Apolipoproteins; Asthma; Carbon tetrachloride; Carbonic anhydrase; Cell adhesion; Chemokines; Child; Conjunctivitis; Conjunctivitis, Allergic - genetics; Conjunctivitis, Allergic - immunology; Cytokines; Dermatitis; Drug Resistance - genetics; Drug Resistance - immunology; Dust; Female; Gene expression; Gene Expression Profiling; Genes; Glucocorticoids; Graft rejection; Hay fever; Heart diseases; Homology; House dust; Humans; Immune response; Immunodeficiency; Immunoglobulin A; Immunoglobulin E; Immunoglobulin M; Immunoglobulins; Immunosuppressive Agents - therapeutic use; Infections; Inflammation; Insulin; Insulin-like growth factors; Keratoconjunctivitis - genetics; Keratoconjunctivitis - immunology; Kinases; Leukocytes (eosinophilic); Lysozyme; Male; Microorganisms; Middle Aged; Migration; Opacity; Papillae; Phosphatase; Pollen; Primary immunodeficiencies; Proteins; Refractory materials; Rheumatoid arthritis; Ribonuclease MRP; Ribonucleic acid; RNA; Sequence Analysis, RNA; T cell receptors; Tacrolimus - therapeutic use; Transcription factors; Transcriptome; Vector-borne diseases; α2-Macroglobulin
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2018.11.007

To the Editor: Atopic keratoconjunctivitis (AKC) and vernal keratoconjunctivitis are severe chronic forms of allergic conjunctivitis that are often accompanied by the formation of giant papillae in the tarsal conjunctivae (see Fig E1 in this article's Online Repository at www.jacionline.org) with prominent TH2 cytokine profiles.1 Recent studies have demonstrated the efficacy of tacrolimus for the treatment of AKC/vernal keratoconjunctivitis.2 However, there are refractory cases, especially of AKC, despite intense treatments using immune suppressants and glucocorticoids.2 To elucidate the pathophysiological characteristics of refractory AKC, we investigated gene expression profiles using tissues of giant papillae obtained from patients with AKC, refractory to tacrolimus treatment for more than 8 weeks (clinical information of the patients is presented in Table E1 in this article's Online Repository at www.jacionline.org). [...]we made a list of DEGs including the genes with possible relevance to AKC pathophysiology (Table II). [...]we observed enriched expression of transcripts of defensive molecules against microorganisms, suggesting that reducing the microorganisms burden in patients with AKC might be a novel therapeutic target for refractory AKC. The RNA-seq transcriptome study is useful to elucidate gene pathways relevant to AKC, and provides us with clues to new therapeutic targets.Appendix Gene FPKM (control) FPKM (AKC) log2 (fold change) P value BPIFA1, SPLUNC-1 antimicrobial protein 0 143.10 Inf 5.00 × 10−05 CA2, Carbonic anhydrase 2 0.15 134.83 9.86 .0001 LTF, Lactotransferrin 1.14 277.83 7.93 5.00 × 10−05 POSTN 8.99 2021.92 7.81 5.00 × 10−05 IGHV3-7 1.97 407.73 7.69 5.00 × 10−05 CLC, Eosinophil lysophospholipase 1.25 141.87 6.83 5.00 × 10−05 LTB, Lymphotoxin beta 1.37 153.64 6.81 .0001 KRT6A 11.34 1161.46 6.68 5.00 × 10−05 LYZ, Lysozyme 2.08 163.27 6.29 .0012 CCL13 2.19 169.69 6.28 5.00 × 10−05 IGHG2 18.33 1415.96 6.27 5.00 × 10−05 IGHA2 13.05 904.77 6.12 5.00 × 10−05 IGHV3OR16-13 4.89 330.38 6.08 5.00 × 10−05 IGLV3-21 1.61 105.49 6.03 5.00 × 10−05 IGLV10-54 4.34 256.28 5.89 5.00 × 10−05 KRT16 4.68 260.24 5.80 5.00 × 10−05 IGHG4 5.96 325.74 5.77 5.00 × 10−05 IGLV2-11 12.05 611.05 5.66 5.00 × 10−05 IGKV2-30 5.26 240.37 5.51 .0002 IGLC7 2.36 101.88 5.43 5.00 × 10−05 IGLV2-14 8.72 376.73 5.43 5.00 × 10−05 IGKV4-1 26.12 960.69 5.20 5.00 × 10−05 IGHV5-51 3.57 125.90 5.14 .0002 CCL18 12.62 433.88 5.10 5.00 × 10−05 CPA3 4.80 158.76 5.05 5.00 × 10−05 TRAC