Abstract
BackgroundMannan-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).MethodsIn 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.ResultsMASP-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.ConclusionsIn 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.
Highlights
Rheumatoid arthritis (RA) is an autoimmune disorder with complex etiology which affects approximately 0.5–1.1% of the world population and has an annual incidence of 3 per 10 000 adults [1]
We aimed to investigate whether MASP2 serum levels and MASP2 polymorphisms could influence the susceptibility to rheumatoid arthritis (RA) and its clinical presentation in a population from Southern Brazil
Mannan-binding lectin-associated serine protease 2 (MASP-2) levels were significantly lower in RA patients than in controls and relatives, but did not differ between patient groups with different clinical characteristics
Summary
Rheumatoid arthritis (RA) is an autoimmune disorder with complex etiology which affects approximately 0.5–1.1% of the world population and has an annual incidence of 3 per 10 000 adults [1]. Despite the increasing number of studies aiming at the development of new RA therapy strategies, up to 50% RA patients do not achieve disease remission [3]. Recent genome-wide association studies have confirmed that genetic factors play an important role in the etiology of RA, but many of these factors need to be validated in the Brazilian population [4,5,6]. The important genetic contribution in the development of RA turns relatives of RA patients to be more susceptible to the disease [7,8,9]. MASP-2 remains poorly investigated in rheumatoid arthritis (RA)
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