Defining protective responses to pathogens: cytokine profiles in leprosy lesions

Yamamura, Masatoshi; Uyemura, Koichi; Deans, RJ; Weinberg, Kenneth I.; Rea, T. H.; Br, Bloom; Modlin, R L

doi:10.1126/science.254.5029.277

Cited by 174 publications

(18 citation statements)

References 15 publications

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Section: Resultsmentioning

confidence: 99%

“…Next, to assess the dichotomy beyond cellular vs. humoral response in leprosy lesions [33,34], a comparison of gene expression in MB leprosy (LL+BL+BB) vs. PB (TT+BT) skin lesions was performed. Differential expression analysis with |log 2 FC| � 1 and FDR � 0.01 resulted in 112 DEGs; 69 up-regulated and 43 down-regulated (Fig 5A and S8 Table).…”

Section: Mb and Pb Gene Expression Profiling And Mrna-based Classifiermentioning

confidence: 99%

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A new paradigm for leprosy diagnosis based on host gene expression

et al. 2021

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Transcriptional profiling is a powerful tool to investigate and detect human diseases. In this study, we used bulk RNA-sequencing (RNA-Seq) to compare the transcriptomes in skin lesions of leprosy patients or controls affected by other dermal conditions such as granuloma annulare, a confounder for paucibacillary leprosy. We identified five genes capable of accurately distinguishing multibacillary and paucibacillary leprosy from other skin conditions. Indoleamine 2,3-dioxygenase 1 (IDO1) expression alone was highly discriminatory, followed by TLR10, BLK, CD38, and SLAMF7, whereas the HS3ST2 and CD40LG mRNA separated multi- and paucibacillary leprosy. Finally, from the main differentially expressed genes (DEG) and enriched pathways, we conclude that paucibacillary disease is characterized by epithelioid transformation and granuloma formation, with an exacerbated cellular immune response, while multibacillary leprosy features epithelial-mesenchymal transition with phagocytic and lipid biogenesis patterns in the skin. These findings will help catalyze the development of better diagnostic tools and potential host-based therapeutic interventions. Finally, our data may help elucidate host-pathogen interplay driving disease clinical manifestations.

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Section: Resultsmentioning

confidence: 99%

Section: Mb and Pb Gene Expression Profiling And Mrna-based Classifiermentioning

confidence: 99%

A new paradigm for leprosy diagnosis based on host gene expression

et al. 2021

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“…17 Penelitian lain yang dilakukan oleh Yamamura dkk., 1991 menyatakan bahwa kadar IL-10 pada lesi kulit pasien kusta tipe LL yang secara bermakna meningkat dibandingkan kusta tipe TT. 18 Penelitian yang dilakukan pada RS Muhammad Husein, Palembang dengan melibatkan 40 subjek dengan kusta dan 40 subjek sehat menunjukkan hasil perbedaan signifikan pada kadar IL-10. Rerata kadar IL-10 pada subjek dengan kusta yaitu 13,24 pg/ml sedangkan rerata kadar IL-10 pada kelompok kontrol atau individu sehat yaitu 40,15 pg/ml.…”

Section: Pendahuluanunclassified

Kadar IL-10 plasma berkorelasi positif dengan kadar IgM anti PGL-1 pada narakontak serumah pasien kusta tipe multibasiler

Priyadarshini

Suryawati

Rusyati

2022

Intisari Sains Medis

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Introduction: A healthy person who contacts people diagnosed with leprosy can be at a high risk of being infected with leprosy with a predominance of the subclinical stage. The MB type infection has a 4-10 times greater risk of developing into a clinical form. Early detection of subclinical leprosy is important so that it can play a role in the process of eliminating leprosy. If it is not screened, most of the subclinical stage leprosy can develop into the clinical stage and can cause physical deformities. Phenolic glycolipid-1 (PGL-1) is a specific antigen for M.leprae and Interleukin-10 (IL-10) is an anti-inflammatory cytokine that shows the body's immune response. Research on the relationship between levels of IL-10 and IgM anti-PGL-1, especially in Bali, has not been carried out, so this study aims to find a relationship between levels of IL-10 and levels of IgM anti-PGL-1 in household contacts of multibacillary leprosy patients. Methods: This research is an analytical observational study with a cross-sectional and was carried out in February-May 2021 at the Dermatology and Venereology Polyclinic and Clinical Pathology Laboratory, Sanglah Hospital Denpasar, and the Leprosy reference laboratory, Tropical Diseases Center, Universitas Airlangga. Samples aged 18-65 years were selected through Consecutive Sampling according to inclusion and exclusion criteria. The sample was taken from venous blood and then checked for levels of PGL-1 and IL-10. Data analysis using SPSS version 23. The results were considered significant if p<0.05. Results: The mean level of IgM anti-PGL-1 in the contact group vs. the non-contact group was 863.07 ± 789.04 u/ml vs 247.75 ± 161.60 u/ml. The mean levels of IL-10 in the contact and non-contact groups were 121.09 ± 144.11 pg/ml and 46.04 ± 11.27 pg/ml. There was a significant difference in levels of IL-10 and IgM anti-PGL-1 in the contact group and non-contact groups (p<0.05) and a weak positive relationship (r=0.296, p=0.02) between levels of IL-10 and anti-PGL-IgM. 1. Conclusion: The levels of IgM anti-PGL-1 and IL-10 in the contacts were higher than in the non-contacts with a significant difference. Pendahuluan: Narakontak merupakan salah satu kelompok dengan risiko tinggi terinfeksi kusta dengan dominansi stadium subklinis. Pada infeksi tipe MB memiliki resiko 4-10 kali lebih besar berkembang menjadi bentuk klinis. Deteksi dini pada penyakit kusta subklinis ini menjadi penting sehingga dapat berperan dalam proses eliminasi kusta. Jika dibiarkan sebagian besar kusta stadium subklinis dapat berkembang menjadi kusta klinis dan dapat menimbulkan deformitas pada fisik. Phenolic glycolipid-1 (PGL-1) merupakan antigen spesifik untuk M. leprae dan Interleukin-10 (IL-10) merupakan sitokin anti-inflamasi yang menunjukkan respon imun tubuh. Penelitian mengenai hubungan antara kadar IL-10 dan IgM anti PGL-1 khusunya di Bali belum dilakukan, sehingga penelitian ini bertujuan mencari hubungan antara kadar IL-10 dengan kadar IgM anti PGL-1 pada narakontak serumah pasien kusta tipe multibasiler. Metode: Penelitian merupakan studi observasional analitik dengan pendekatan potong lintang dan dilaksanakan bulan Februari-Mei 2021 di Poliklinik Kulit dan Kelamin dan Laboratorium Patologi Klinik, RSUP Sanglah Denpasar dan laboratorium rujukan Leprosy, Tropical Diseases Centre, Universitas Airlangga. Sampel berusia 18-65 tahun dipilih melalui Consecutive Sampling sesuai kriteria inklusi dan eksklusi. Sampel dilakukan pengambilan darah vena kemudian diperiksa kadar PGL-1 dan IL-10. Analisis data menggunakan SPSS versi 23. Hasil dianggap signifikan jika p<0,05. Hasil: Rerata kadar IgM anti PGL-1 kelompok narakontak vs bukan narakontak sebesar 863,07 ± 789,04 u/ml vs 247,75 ± 161,60 u/ml. Rerata kadar IL-10 kelompok narakontak dan bukan narakontak sebesar 121,09 ± 144,11 pg/ml dan 46,04 ± 11,27 pg/ml. Terdapat perbedaan signifikan pada kadar IL-10 dan IgM anti PGL-1 pada kelompok narakontak dan bukan narakontak (p<0.05) serta hubungan positif lemah (r=0,296, p=0,02) antara kadar IL-10 dengan IgM anti PGL-1. Simpulan: Kadar IgM anti PGL-1 dan IL-10 pada narakontak lebih tinggi dari non narakontak dengan perbedaan yang signifikan.

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“…The PCR primers of IL-1β, TNF-α and G3PDH were designed, and RT-PCR was performed as described previously. [14][15][16][17] Quantitative RT-PCR for IL-1β and TNF-α was performed normalized to the copies of GAPDH mRNA from the same sample. The experiments were conducted in duplicate, and the results were calculated as mean values.…”

Section: Il-1β and Tnf-α Mrna Gene Expressionmentioning

confidence: 99%