Lectin pathway factors in patients suffering from juvenile idiopathic arthritis

Abstract

Both complement activation and certain infections (including those with Yersinia sp.) may contribute to the pathogenesis of juvenile idiopathic arthritis (JIA). We investigated factors specific for the lectin pathway of complement: mannose-binding lectin (MBL), ficolins and MBL-associated serine protease-2 (MASP-2), in 144 patients and 98 controls. One hundred and six patients had oligoarticular disease and 38 had polyarticular disease. In 51 patients (out of 133 tested), Yersinia-reactive antibodies were found (JIA Ye group). MBL deficiency was significantly more frequent in the JIA Ye group than in patients without Yersinia-reactive antibodies or in controls. Median serum ficolin-2 level was significantly lower (and proportion of values deemed ficolin-2 insufficient greater) in JIA patients irrespective of their Yersinia antibody status. The minority (C) allele at -64 of the FCN2 gene was less frequent among JIA patients than among control subjects. No differences were found in the frequency of FCN3 gene +1637delC or MASP2 +359 A>G mutations nor for median values of serum ficolin-1, ficolin-3 or MASP-2. However, high levels of serum ficolin-3 were under-represented in patients, in contrast to MBL. MBL, ficolin-1, ficolin-2, ficolin-3 and MASP-2 were also readily detectable in synovial fluid samples but at a considerably lower level than in serum. Our findings suggest a possible role for the lectin pathway in the pathogenesis of JIA, perhaps secondary to a role in host defence, and indicate that investigations on the specificity of lectin pathway recognition molecules towards specific infectious agents in JIA might be fruitful.

Association between serum ficolin-1 level and disease progression in primary biliary cholangitis

“…High serum MBL level was reported to be associated with thrombocytopenia and seizure in patients with SLE [22], and serum MBL was reported to be positively correlated with Birmingham Vasculitis Activity Score in patients with antineutrophil cytoplasmic antibody-associated vasculitis [23]. In addition, serum ficolin-1 was positively correlated with disease activity in patients with rheumatoid arthritis (RA) [24] and juvenile idiopathic arthritis [25]. Upregulated mRNA levels of ficolin-1 in peripheral blood mononuclear cells, and a lot of ficolin-1-positive monocytes in the glomeruli in patients with microscopic polyangiitis have also been reported [26].…”

The Clinical Value of Ficolin-3 Gene Polymorphism in Rheumatic Heart Disease. An Egyptian Adolescents Study

“…Ficolin-3 is encoded by the FCN3 gene which is located on chromosome 1p36 and contains eight exons. Few studies showed an association between collectin and colin genes polymorphisms and infectious and autoimmune diseases [31][32][33][34][35][36]. It was shown that there are some associations between gene polymorphisms of MBL [37][38][39][40], Ficolin-1 [16], Ficolin-2 [41] [42], and MASP-2 [43] with RF.…”

Complement lectin pathway protein levels reflect disease activity in juvenile idiopathic arthritis: a longitudinal study of the Nordic JIA cohort

“…There is an increasing body of evidence that inadequately controlled activation of complement factors leading to either overactivity or deficiency may be involved in the pathogenesis of some autoimmune diseases [3–6]. However, the role of the complement system in JIA is still not fully elucidated [7–11]. Most studies involve investigations of the classical and the alternative pathway and have shown contradictory results [7, 9, 12–14].…”

“…Studies on the remaining lectin pathway proteins in JIA are scarce [11, 24]. In 2015, Petri et al [24] compared the lectin pathway protein levels in patients with oligoarticular and systemic JIA (sJIA).…”

“…Additionally, M-ficolin levels correlated positively to the number of active joints. In JIA patients, Kasperkiewicz et al [11] found no differences in the levels of M-ficolin or MASP-2 compared to controls but L-ficolin levels were lower in the oligoarticular JIA group. However, this was not related to clinical parameters.…”