title: Leprosy reactions: The predictive value of Mycobacterium leprae-specific serology evaluated in a Brazilian cohort of leprosy patients (U-MDT/CT-BR).
abstract: Leprosy reactions, reversal reactions/RR and erythema nodosum leprosum/ENL, can cause irreversible nerve damage, handicaps and deformities. The study of Mycobacterium leprae-specific serologic responses at diagnosis in the cohort of patients enrolled at the Clinical Trial for Uniform Multidrug Therapy Regimen for Leprosy Patients in Brazil/U-MDT/CT-BR is suitable to evaluate its prognostic value for the development of reactions.
  
  
  
  IgM and IgG antibody responses to PGL-I, LID-1, ND-O-LID were evaluated by ELISA in 452 reaction-free leprosy patients at diagnosis, enrolled and monitored for the development of leprosy reactions during a total person-time of 780,930 person-days, i.e. 2139.5 person-years, with a maximum of 6.66 years follow-up time.
  
  
  
  Among these patients, 36% (160/452) developed reactions during follow-up: 26% (119/452) RR and 10% (41/452) had ENL. At baseline higher anti-PGL-I, anti-LID-1 and anti-ND-O-LID seropositivity rates were seen in patients who developed ENL and RR compared to reaction-free patients (p<0.0001). Seroreactivity in reactional and reaction-free patients was stratified by bacilloscopic index/BI categories. Among BI negative patients, higher anti-PGL-I levels were seen in RR compared to reaction-free patients (p = 0.014). In patients with 0<BI<3, (36 RR, 36 reaction-free), higher antibody levels to PGL-I (p = 0.014) and to LID-1 (p = 0.035) were seen in RR while difference in anti-ND-O-LID positivity was borderline (p = 0.052). Patients with BI≥3 that developed ENL had higher levels of anti-LID-1 antibodies (p = 0.028) compared to reaction-free patients. Anti-PGL-I serology had a limited predictive value for RR according to receiver operating curve/ROC analyses (area-under-the-curve/AUC = 0.7). Anti LID-1 serology at baseline showed the best performance to predict ENL (AUC 0.85).
  
  
  
  Overall, detection of anti-PGL-I, anti-LID-1 and anti-ND-O-LID antibodies at diagnosis, showed low sensitivity and specificity for RR prediction, indicating low applicability of serological tests for RR prognosis. On the other hand, anti-LID-1 serology at diagnosis has shown prognostic value for ENL development in BI positive patients.
  
  
  
  ClinicalTrials.gov NCT00669643.
authors.affiliation: Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, GO, Brasil.
authors.forename: Emerith Mayra
authors.initials: EM
authors.lastname: Hungria
authors.affiliation: Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, GO, Brasil.
authors.forename: Samira
authors.identifier: 0000-0002-5984-7770
authors.initials: S
authors.lastname: Bührer-Sékula
authors.affiliation: Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, GO, Brasil.
authors.forename: Regiane Morillas
authors.initials: RM
authors.lastname: de Oliveira
authors.affiliation: Centro de Dermatologia Dona Libânia, Fortaleza, Ceará, Brasil.
authors.forename: Lúcio Cartaxo
authors.initials: LC
authors.lastname: Aderaldo
authors.affiliation: Centro de Dermatologia Dona Libânia, Fortaleza, Ceará, Brasil.
authors.forename: Araci de Andrade
authors.initials: AA
authors.lastname: Pontes
authors.affiliation: Fundação de Dermatologia Tropical e Venereologia Alfredo da Matta, Manaus, Amazonas, Brasil.
authors.forename: Rossilene
authors.initials: R
authors.lastname: Cruz
authors.affiliation: Centro de Dermatologia Dona Libânia, Fortaleza, Ceará, Brasil.
authors.forename: Heitor de Sá
authors.initials: HS
authors.lastname: Gonçalves
authors.affiliation: Departamento de Epidemiologia e Bioestatística, Universidade Federal Fluminense, Rio de Janeiro, Rio de Janeiro, Brasil.
authors.forename: Maria Lúcia Fernandes
authors.initials: ML
authors.lastname: Penna
authors.affiliation: Núcleo de Medicina Tropical, Universidade de Brasília, Brasília, DF, Brasil.
authors.forename: Gerson Oliveira
authors.initials: GO
authors.lastname: Penna
authors.affiliation: Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, GO, Brasil.
authors.forename: Mariane Martins de Araújo
authors.initials: MM
authors.lastname: Stefani
mesh_terms: D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood*; D001938:Brazil; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007918:Leprosy / Q000175:diagnosis*; D008297:Male; D009166:Mycobacterium leprae / Q000276:immunology*; D011237:Predictive Value of Tests; D011379:Prognosis; D012680:Sensitivity and Specificity; D012698:Serologic Tests / Q000379:methods*
chemical_list: D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D007075:Immunoglobulin M