Transcriptional changes that characterize the immune reactions of leprosy.
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.
Division of Infectious Diseases and Center for Global Health, Weill Cornell Medical College, New York, New York.
Kathryn M
KM
Dupnik
Iowa Institute for Human Genetics, University of Iowa.
Thomas B
TB
Bair
Department of Biochemistry.
Andressa O
AO
Maia
Department of Biochemistry.
Francianne M
FM
Amorim
Brain Institute.
Marcos R
MR
Costa
Department of Biochemistry.
Tatjana S L
TS
Keesen
Department of Biochemistry.
Joanna G
JG
Valverde
Hospital Onofre Lopes.
Maria do Carmo A P
Mdo C
Queiroz
Secretaria da Saúde, Mossoró, Rio Grande do Norte.
Lúcio L
LL
Medeiros
Laboratório Luchiari.
Nelly L
NL
de Lucena
Departments of Internal Medicine and Microbiology, University of Iowa and the VA Medical Center, Iowa City.
Mary E
ME
Wilson
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.
Mauricio L
ML
Nobre
Division of Infectious Diseases and Center for Global Health, Weill Cornell Medical College, New York, New York.
Warren D
WD
Johnson
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.
Selma M B
SM
Jeronimo
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003165:Complement System Proteins / Q000276:immunology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D007918:Leprosy / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D012867:Skin / Q000473:pathology; D055815:Young Adult
D003165:Complement System Proteins
complement; erythema nodosum leprosum; leprosy; reversal reaction