title: Association of MASP-2 levels and MASP2 gene polymorphisms with rheumatoid arthritis in patients and their relatives.
abstract: BACKGROUND
  Mannan-binding lectin-associated serine protease 2 (MASP-2) is a key protein of the lectin pathway of complement. MASP-2 levels have been associated with different polymorphisms within MASP2 gene as well as with the risk for inflammatory disorders and infections. Despite its clinical importance, MASP-2 remains poorly investigated in rheumatoid arthritis (RA).
  
  
  METHODS
  In this case-control study, we measured MASP-2 serum levels in 156 RA patients, 44 patient relatives, and 100 controls from Southern Brazil, associating the results with nine MASP2 polymorphisms in all patients, 111 relatives, and 230 controls genotyped with multiplex SSP-PCR.
  
  
  RESULTS
  MASP-2 levels were lower in patients than in controls and relatives (medians 181 vs. 340 or 285 ng/ml, respectively, P<0.0001). Conversely, high MASP-2 levels were associated with lower susceptibility to RA and to articular symptoms independently of age, gender, ethnicity, smoking habit, anti-CCP and rheumatoid factor positivity (OR = 0.05 [95%CI = 0.019-0.13], P<0.0001 between patients and controls; OR = 0.12, [95%CI = 0.03-0.45], P = 0.002 between patients and relatives; OR = 0.06, [95%CI = 0.004-0.73], P = 0.03 between relatives with and without articular symptoms). MASP2 haplotypes *2A1 and *2B1-i were associated with increased susceptibility to RA (OR = 3.32 [95%CI = 1.48-7.45], P = 0.004). Deficiency-causing p.120G and p.439H substitutions were associated with five times increased susceptibility to articular symptoms in relatives (OR = 5.13 [95%CI = 1.36-20.84], P = 0.02). There was no association of MASP-2 levels or MASP2 polymorphisms with autoantibodies, Sjögren's syndrome, nodules and functional class.
  
  
  CONCLUSIONS
  In this study, we found the first evidence that MASP-2 deficiency might play an important role in the development of RA and articular symptoms among relatives of RA patients.
authors.affiliation: Department of Medical Pathology, Federal University of Paraná, Curitiba, Brazil.
authors.forename: Isabela
authors.initials: I
authors.lastname: Goeldner
authors.affiliation: Rheumatology Unit, Evangelical University Hospital, Curitiba, Brazil.
authors.forename: Thelma
authors.initials: T
authors.lastname: Skare
authors.affiliation: Department of Medical Pathology, Federal University of Paraná, Curitiba, Brazil.
authors.forename: Angelica B W
authors.initials: AB
authors.lastname: Boldt
authors.affiliation: Department of Medical Pathology, Federal University of Paraná, Curitiba, Brazil.
authors.forename: Flavia R
authors.initials: FR
authors.lastname: Nass
authors.affiliation: Department of Medical Pathology, Federal University of Paraná, Curitiba, Brazil.
authors.forename: Iara J
authors.initials: IJ
authors.lastname: Messias-Reason
authors.affiliation: Department of Clinical Analysis, Federal University of Paraná, Curitiba, Brazil.
authors.forename: Shirley R
authors.initials: SR
authors.lastname: Utiyama
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D055815:Young Adult
chemical_list: C105296:MASP2 protein, human; D050606:Mannose-Binding Protein-Associated Serine Proteases