title: Hypocomplementaemia as an immunological marker of morbidity and mortality in patients with primary Sjogren's syndrome.
abstract: OBJECTIVE
  To analyse the prevalence and clinical significance of hypocomplementaemia in a large series of patients with primary Sjogren's syndrome (SS), focusing on the association of low complement levels with clinical manifestations, immunological features, lymphoproliferative disorders and mortality.
  
  
  METHODS
  Complement determinations (C3 and C4 levels, CH50 activity) were made in 336 consecutive patients with primary SS (313 women and 23 men, mean age 58.5 yr). We also analysed complement levels in 46 patients with SS associated with hepatitis C virus (HCV) infection and 184 with HCV-related cryoglobulinaemia as control groups.
  
  
  RESULTS
  Hypocomplementaemia was detected in 81 (24%) of patients with primary SS, low CH50 being detected in 51 (15%), low C3 values in 42 (12%) and low C4 values in 39 (12%). In the multivariate analysis, patients with low C4 levels showed a higher prevalence of peripheral neuropathy, cutaneous vasculitis, RF, cryoglobulins and lymphoma compared with those with normal C4 levels. The analysis of the 218 SS patients followed prospectively since 1994 showed a lower probability of survival in patients with hypocomplementaemia (with low C3, C4 or CH50 levels) at protocol entry. SS-HCV patients presented a higher frequency of hypocomplementaemia than patients with primary SS (76 vs 24%, P<0.001); nine (20%) of these patients had persistent, unquantifiable complement levels.
  
  
  CONCLUSIONS
  Hypocomplementaemia is closely associated with systemic expression and adverse outcomes (lymphoma development and death) in patients with primary SS. Our results support the inclusion of complement determination at diagnosis as a predictor of the outcome of patients with primary SS and its routine determination in the clinical follow-up.
authors.affiliation: Department of Autoimmune Diseases, Institut d'Investigacions Biomédiques Augst Pi i Sunyer (IDIBAPS) Hospital Clinic, School of Medicine, Univesity of Barcelona, Spain. mramos@clinic.ub.es
authors.forename: M
authors.initials: M
authors.lastname: Ramos-Casals
authors.forename: P
authors.initials: P
authors.lastname: Brito-Zerón
authors.forename: J
authors.initials: J
authors.lastname: Yagüe
authors.forename: M
authors.initials: M
authors.lastname: Akasbi
authors.forename: R
authors.initials: R
authors.lastname: Bautista
authors.forename: M
authors.initials: M
authors.lastname: Ruano
authors.forename: G
authors.initials: G
authors.lastname: Claver
authors.forename: V
authors.initials: V
authors.lastname: Gil
authors.forename: J
authors.initials: J
authors.lastname: Font
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D003176:Complement C3 / Q000032:analysis / Q000172:deficiency; D003181:Complement C4 / Q000032:analysis / Q000172:deficiency; D015941:Complement Hemolytic Activity Assay; D003165:Complement System Proteins / Q000032:analysis / Q000172:deficiency*; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications / Q000276:immunology; D006801:Humans; D008223:Lymphoma / Q000209:etiology / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012859:Sjogren's Syndrome / Q000150:complications / Q000276:immunology*; D016019:Survival Analysis
chemical_list: D015415:Biomarkers; D003176:Complement C3; D003181:Complement C4; D003165:Complement System Proteins