title: Expression of CD64 on Circulating Neutrophils Favoring Systemic Inflammatory Status in Erythema Nodosum Leprosum.
abstract: Erythema Nodosum Leprosum (ENL) is an immune reaction in leprosy that aggravates the patient´s clinical condition. ENL presents systemic symptoms of an acute infectious syndrome with high leukocytosis and intense malaise clinically similar to sepsis. The treatment of ENL patients requires immunosuppression and thus needs to be early and efficient to prevent both disabilities and permanent nerve damage. Some patients experience multiple episodes of ENL and prolonged use of immunosuppressive drugs may lead to serious adverse effects. Thalidomide treatment is extremely effective at ameliorating ENL symptoms. Several mechanisms have been proposed to explain the efficacy of thalidomide in ENL, including the inhibition of TNF production. Given its teratogenicity, thalidomide is prohibitive for women of childbearing age. A rational search for molecular targets during ENL episodes is essential to better understand the disease mechanisms involved, which may also lead to the discovery of new drugs and diagnostic tests. Previous studies have demonstrated that IFN-γ and GM-CSF, involved in the induction of CD64 expression, increase during ENL. The aim of the present study was to investigate CD64 expression during ENL and whether thalidomide treatment modulated its expression. Leprosy patients were allocated to one of five groups: (1) Lepromatous leprosy, (2) Borderline leprosy, (3) Reversal reaction, (4) ENL, and (5) ENL 7 days after thalidomide treatment. The present study demonstrated that CD64 mRNA and protein were expressed in ENL lesions and that thalidomide treatment reduced CD64 expression and neutrophil infiltrates-a hallmark of ENL. We also showed that ENL blood neutrophils exclusively expressed CD64 on the cell surface and that thalidomide diminished overall expression. Patient classification based on clinical symptoms found that severe ENL presented high levels of neutrophil CD64. Collectively, these data revealed that ENL neutrophils express CD64, presumably contributing to the immunopathogenesis of the disease.
authors.affiliation: Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
authors.forename: Veronica
authors.identifier: 0000-0002-0865-133X
authors.initials: V
authors.lastname: Schmitz
authors.affiliation: Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
authors.forename: Rhana Berto da Silva
authors.initials: RB
authors.lastname: Prata
authors.affiliation: Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
authors.forename: Mayara Garcia de Mattos
authors.initials: MG
authors.lastname: Barbosa
authors.affiliation: Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
authors.forename: Mayara Abud
authors.initials: MA
authors.lastname: Mendes
authors.affiliation: Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
authors.forename: Sheila Santos
authors.initials: SS
authors.lastname: Brandão
authors.affiliation: Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Thaís Porto
authors.initials: TP
authors.lastname: Amadeu
authors.affiliation: Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Luciana Silva
authors.initials: LS
authors.lastname: Rodrigues
authors.affiliation: Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
authors.forename: Helen
authors.initials: H
authors.lastname: Ferreira
authors.affiliation: Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
authors.forename: Fabrício da Mota Ramalho
authors.initials: Fda M
authors.lastname: Costa
authors.affiliation: Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
authors.forename: Jessica Brandão
authors.initials: JB
authors.lastname: Dos Santos
authors.affiliation: Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
authors.forename: Fabiana Dos Santos
authors.initials: Fdos S
authors.lastname: Pacheco
authors.affiliation: Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
authors.forename: Alice de Miranda
authors.initials: Ade M
authors.lastname: Machado
authors.affiliation: Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
authors.forename: José Augusto da Costa
authors.initials: JA
authors.lastname: Nery
authors.affiliation: Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
authors.forename: Mariana de Andrea
authors.initials: Mde A
authors.lastname: Hacker
authors.affiliation: Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Sales
authors.affiliation: Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
authors.forename: Roberta Olmo
authors.initials: RO
authors.lastname: Pinheiro
authors.affiliation: Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
authors.forename: Euzenir Nunes
authors.initials: EN
authors.lastname: Sarno
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D004893:Erythema Nodosum / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology; D005260:Female; D006801:Humans; D007917:Leprostatic Agents / Q000627:therapeutic use*; D015439:Leprosy, Borderline / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology; D015440:Leprosy, Lepromatous / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology*; D017452:Receptors, IgG / Q000235:genetics* / Q000276:immunology; D012867:Skin / Q000382:microbiology / Q000473:pathology; D013792:Thalidomide / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D007917:Leprostatic Agents; D017452:Receptors, IgG; D013792:Thalidomide