Lectin pathway factors in patients suffering from juvenile idiopathic arthritis

Immunol Cell Biol. 2017 Sep;95(8):666-675. doi: 10.1038/icb.2017.31. Epub 2017 Apr 13.

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.

MeSH terms

  • Adolescent
  • Antibodies, Bacterial / blood
  • Arthritis, Juvenile / epidemiology
  • Arthritis, Juvenile / immunology*
  • Child
  • Child, Preschool
  • Complement Pathway, Mannose-Binding Lectin / genetics*
  • Ficolins
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Glycoproteins / genetics
  • Humans
  • Infant
  • Lectins / genetics*
  • Male
  • Mannose-Binding Lectin / genetics*
  • Mannose-Binding Protein-Associated Serine Proteases / genetics
  • Polymorphism, Genetic
  • Yersinia Infections / epidemiology
  • Yersinia Infections / immunology*
  • Yersinia enterocolitica / immunology*
  • Yersinia pseudotuberculosis / immunology*

Substances

  • Antibodies, Bacterial
  • FCN3 protein, human
  • Glycoproteins
  • Lectins
  • MBL2 protein, human
  • Mannose-Binding Lectin
  • MASP2 protein, human
  • Mannose-Binding Protein-Associated Serine Proteases