title: Complement C4 deficiency--a plausible risk factor for non-tuberculous mycobacteria (NTM) infection in apparently immunocompetent patients.
abstract: BACKGROUND
  Non-tuberculous mycobacteria (NTM) are ubiquitous in the environment and they infect mainly persons with underlying pulmonary diseases but also previously healthy elderly women. Defects in host resistance that lead to pulmonary infections by NTM are relatively unknown. A few genetic defects have been associated with both pulmonary and disseminated mycobacterial infections. Rare disseminated NTM infections have been associated with genetic defects in T-cell mediated immunity and in cytokine signaling in families. We investigated whether there was an association between NTM infections and deficiencies of complement components C4A or C4B that are encoded by major histocompatibility complex (MHC).
  
  
  METHODS
  50 adult patients with a positive NTM culture with symptoms and findings of a NTM disease were recruited. Patients' clinical history was collected and symptoms and clinical findings were categorized according to 2007 diagnostic criteria of The American Thoracic Society (ATS). To investigate the deficiencies of complement, C4A and C4B gene copy numbers and phenotype frequencies of the C4 allotypes were analyzed. Unselected, healthy, 149 Finnish adults were used as controls.
  
  
  RESULTS
  NTM patients had more often C4 deficiencies (C4A or C4B) than controls (36/50 [72%] vs 83/149 [56%], OR = 2.05, 95%CI = 1.019-4.105, p = 0.042). C4 deficiencies for female NTM patients were more common than for controls (29/36 [81%] vs 55/100 [55%], OR = 3.39, 95% CI = 1.358-8.460, p = 0.007). C4 deficiences seemed not to be related to any specific underlying disease or C4 phenotype.
  
  
  CONCLUSIONS
  C4 deficiency may be a risk factor for NTM infection in especially elderly female patients.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Hannele
authors.initials: H
authors.lastname: Kotilainen
authors.affiliation: Transplantation Laboratory, Haartman Institute, University of Helsinki, Helsinki, Finland.
authors.forename: Marja-Liisa
authors.initials: ML
authors.lastname: Lokki
authors.affiliation: Transplantation Laboratory, Haartman Institute, University of Helsinki, Helsinki, Finland; Division of Cardiology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Riitta
authors.initials: R
authors.lastname: Paakkanen
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Mikko
authors.initials: M
authors.lastname: Seppänen
authors.affiliation: Division of Lung Diseases, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Pentti
authors.initials: P
authors.lastname: Tukiainen
authors.affiliation: Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Helsinki, Finland.
authors.forename: Seppo
authors.initials: S
authors.lastname: Meri
authors.affiliation: STAT-Consulting, Nokia, Finland.
authors.forename: Tuija
authors.initials: T
authors.lastname: Poussa
authors.affiliation: Mycobacteriology Unit, Helsinki University Central Hospital Laboratory, Helsinki, Finland.
authors.forename: Jussi
authors.initials: J
authors.lastname: Eskola
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Ville
authors.initials: V
authors.lastname: Valtonen
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Asko
authors.initials: A
authors.lastname: Järvinen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D003181:Complement C4 / Q000172:deficiency* / Q000235:genetics; D004198:Disease Susceptibility / Q000276:immunology; D005260:Female; D005387:Finland; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009165:Mycobacterium Infections, Nontuberculous / Q000175:diagnosis / Q000209:etiology*; D009170:Nontuberculous Mycobacteria / Q000276:immunology*; D010641:Phenotype; D012307:Risk Factors
chemical_list: D003181:Complement C4