Mannose-binding lectin-low genotypes are associated with milder systemic and immunological disease expression in primary Sjögren's syndrome

Rheumatology (Oxford). 2009 Jan;48(1):65-9. doi: 10.1093/rheumatology/ken411.

Abstract

Objective: To investigate the association of mannose-binding lectin (MBL)-low genotypes with the clinical and immunological expression of primary SS.

Methods: Eighty-one patients with primary SS who fulfilled the 2002 classification criteria were included in the study. MBL2 polymorphisms were investigated by sequence-based DNA typing of the promoter and exon 1. Genotypes 0/0, 0/XA or XA/XA were considered as MBL-low and XA/A, A/0 and A/A as MBL-sufficient. Control groups included 46 patients who exclusively fulfilled the 1993 SS criteria, 114 SLE patients and 104 healthy individuals.

Results: Twelve (15%) SS patients had MBL-low genotypes, of whom six (7%) had genotype 0/XA, five (6%) had genotype 0/0 and one (1%) had genotype XA/XA. A higher prevalence of the XA/A genotype (32 vs 17%, P = 0.01) was found in primary SS patients in comparison with SLE patients. No patient with primary SS carrying MBL-low genotypes had purpura, glomerulonephritis or neurological involvement (0 vs 29%, P = 0.025). Immunologically, patients carrying MBL-low genotypes had a lower frequency of anti-Ro/SS-A antibodies (17 vs 55%, P = 0.014), anti-La/SS-B antibodies (8 vs 48%, P = 0.009) and low C4/C3 levels (0 vs 32%, P = 0.016). No patient with primary SS carrying the homozygous MBL-deficient genotype 0/0 had anti-Ro/SS-A or anti-La/SS-B antibodies, low C3/C4 levels or circulating cryoglobulins.

Conclusion: SS patients with MBL-low genotypes have a less pronounced systemic and immunological disease expression in comparison with those carrying MBL-sufficient genotypes. In primary SS, MBL deficiency may represent a protective factor against the development of more aggressive autoimmune damage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoantibodies / blood
  • Autoantigens / immunology
  • Biomarkers / blood
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Immunity, Innate
  • Male
  • Mannose-Binding Lectin / genetics*
  • Mannose-Binding Protein-Associated Serine Proteases / genetics
  • Middle Aged
  • Polymorphism, Genetic
  • RNA, Small Cytoplasmic / immunology
  • Retrospective Studies
  • Ribonucleoproteins / immunology
  • Sjogren's Syndrome / genetics*
  • Sjogren's Syndrome / immunology

Substances

  • Autoantibodies
  • Autoantigens
  • Biomarkers
  • MBL2 protein, human
  • Mannose-Binding Lectin
  • RNA, Small Cytoplasmic
  • RO60 protein, human
  • Ribonucleoproteins
  • MASP2 protein, human
  • Mannose-Binding Protein-Associated Serine Proteases