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J Infect Dis. 2015 May 15;211(10):1658-76. doi: 10.1093/infdis/jiu612. Epub 2014 Nov 14.

Transcriptional changes that characterize the immune reactions of leprosy.

Author information

1
Division of Infectious Diseases and Center for Global Health, Weill Cornell Medical College, New York, New York.
2
Iowa Institute for Human Genetics, University of Iowa.
3
Department of Biochemistry.
4
Brain Institute.
5
Hospital Onofre Lopes.
6
Secretaria da Saúde, Mossoró, Rio Grande do Norte.
7
Laboratório Luchiari.
8
Departments of Internal Medicine and Microbiology, University of Iowa and the VA Medical Center, Iowa City.
9
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, Brazil.
10
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.

Abstract

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.

KEYWORDS:

complement; erythema nodosum leprosum; leprosy; reversal reaction

PMID:
25398459
PMCID:
PMC4425823
DOI:
10.1093/infdis/jiu612
[Indexed for MEDLINE]
Free PMC Article

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