Journal article
Transcriptional changes that characterize the immune reactions of leprosy
The Journal of infectious diseases, Vol.211(10), pp.1658-1676
05/15/2015
DOI: 10.1093/infdis/jiu612
PMCID: PMC4425823
PMID: 25398459
Abstract
Leprosy morbidity is increased by 2 pathologic immune reactions, reversal reaction (RR) and erythema nodosum leprosum (ENL).
To discover host factors related to immune reactions, global transcriptional profiles of peripheral blood mononuclear cells were compared between 11 RR, 11 ENL, and 19 matched control patients, with confirmation by quantitative polymerase chain reaction. Encoded proteins were investigated in skin biopsy specimens by means of immunohistochemistry.
There were 275 genes differentially expressed in RR and 517 differentially expressed in ENL on the microarray. Pathway analysis showed immunity-related pathways represented in RR and ENL transcriptional profiles, with the "complement and coagulation" pathway common to both. Interferon γ was identified as a significant upstream regulator of the expression changes for RR and ENL. Immunohistochemical staining of skin lesions showed increased C1q in both RR and ENL.
These data suggest a previously underrecognized role for complement in the pathogenesis of both RR and ENL, and we propose new hypotheses for reaction pathogenesis.
Details
- Title: Subtitle
- Transcriptional changes that characterize the immune reactions of leprosy
- Creators
- Kathryn M Dupnik - Division of Infectious Diseases and Center for Global Health, Weill Cornell Medical College, New York, New YorkThomas B Bair - Iowa Institute for Human Genetics, University of IowaAndressa O Maia - Department of BiochemistryFrancianne M Amorim - Department of BiochemistryMarcos R Costa - Brain InstituteTatjana S L Keesen - Department of BiochemistryJoanna G Valverde - Department of BiochemistryMaria do Carmo A P Queiroz - Hospital Onofre LopesLúcio L Medeiros - Secretaria da Saúde, Mossoró, Rio Grande do NorteNelly L de Lucena - Laboratório LuchiariMary E Wilson - Departments of Internal Medicine and Microbiology, University of Iowa and the VA Medical Center, Iowa CityMauricio L Nobre - Hospital Giselda Trigueiro, Natal Institute of Tropical Medicine of Rio Grande do Norte, Universidade Federal do Rio Grande do Norte Post-graduate Program in Tropical Medicine, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro National Institute of Science and Technology of Tropical Diseases, Salvador, Bahia, BrazilWarren D Johnson Jr - Division of Infectious Diseases and Center for Global Health, Weill Cornell Medical College, New York, New YorkSelma M B Jeronimo - Department of Biochemistry Institute of Tropical Medicine of Rio Grande do Norte, Universidade Federal do Rio Grande do Norte National Institute of Science and Technology of Tropical Diseases, Salvador, Bahia, Brazil
- Resource Type
- Journal article
- Publication Details
- The Journal of infectious diseases, Vol.211(10), pp.1658-1676
- Publisher
- United States
- DOI
- 10.1093/infdis/jiu612
- PMID
- 25398459
- PMCID
- PMC4425823
- ISSN
- 1537-6613
- eISSN
- 1537-6613
- Grant note
- T32 AI007613 / NIAID NIH HHS T32-AI007613 / NIAID NIH HHS R01 AI048822 / NIAID NIH HHS I01 BX001983 / BLRD VA R25-TW009337-02 / FIC NIH HHS R25 TW009337 / FIC NIH HHS
- Language
- English
- Date published
- 05/15/2015
- Academic Unit
- Microbiology and Immunology; International Programs; Epidemiology; Internal Medicine
- Record Identifier
- 9984001200802771
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