Transcriptional changes that characterize the immune reactions of leprosy
| Autor: | Francianne M. Amorim, Tatjana Souza Lima Keesen, Nelly L. de Lucena, Lúcio L. Medeiros, Andressa O. Maia, Warren D. Johnson, Mary E. Wilson, Marcos R. Costa, Thomas B. Bair, Selma M. B. Jeronimo, Kathryn M. Dupnik, Joanna G. Valverde, Maria do Carmo Palmeira Queiroz, Mauricio Lisboa Nobre |
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| Rok vydání: | 2014 |
| Předmět: |
Adult
Male Microarray Biology Real-Time Polymerase Chain Reaction Peripheral blood mononuclear cell Pathogenesis Young Adult Major Articles and Brief Reports Leprosy medicine erythema nodosum leprosum Immunology and Allergy Humans complement skin and connective tissue diseases Aged Skin medicine.diagnostic_test integumentary system Microarray analysis techniques Gene Expression Profiling Complement System Proteins biochemical phenomena metabolism and nutrition Middle Aged Microarray Analysis Immunohistochemistry Gene expression profiling Infectious Diseases Real-time polymerase chain reaction reversal reaction Case-Control Studies Skin biopsy Immunology Leukocytes Mononuclear Female leprosy |
| Zdroj: | Repositório Institucional da UFRN Universidade Federal do Rio Grande do Norte (UFRN) instacron:UFRN |
| ISSN: | 1537-6613 |
| Popis: | Background: Leprosy morbidity is increased by 2 pathologic immune reactions, reversal reaction (RR) and erythema nodosum leprosum (ENL). Methods: 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. Results: 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. Conclusions: 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. Background: Leprosy morbidity is increased by 2 pathologic immune reactions, reversal reaction (RR) and erythema nodosum leprosum (ENL). Methods: 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. Results: 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. Conclusions: 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. |
| Databáze: | OpenAIRE |
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