Association of high titers of anti-carbamylated protein antibodies with decreased bone mineral density in early arthritis patients

PLoS One. 2018 Aug 17;13(8):e0202583. doi: 10.1371/journal.pone.0202583. eCollection 2018.

Abstract

Rheumatoid arthritis (RA) has a negative impact on bone that is partly mediated by anti-citrullinated proteins antibodies (ACPA). These antibodies are associated with erosions, and with juxta-articular and systemic bone loss. Other RA autoantibodies, the anti-carbamylated protein antibodies (anti-CarPA), are independently associated with erosions. However, we do not know if they are also associated with juxta-articular and systemic bone loss. Here, we have addressed this question with data from 548 early arthritis (EA) patients. Bone mineral density (BMD) was assessed by dual-energy x-ray absorptiometry at the lumbar spine (LS), total hip (TH) and metacarpophalangeal joints (MCP). The 25.9% anti-CarPA positive patients did not show significant differences in BMD Z-scores with the negative patients. Nevertheless, this result was due to the similarity between negative and low-positive (below the median of the positive) patients, whereas the high-positive patients showed significant decrease of BMD at LS (β = -0.39, p = 0.01) and TH (β = -0.30, p = 0.02); but not at the juxta-articular bone of MCP. Given the overlap between anti-CarPA and ACPA, we included the two autoantibodies in an analysis that showed significantly lower BMD Z-scores at LS and TH (p< 0.01) only in the ACPA positive/anti-CarPA high-positive subgroup. However, the similar coefficients of regression between the ACPA positive/anti-CarPA high-positive and the ACPA negative/anti-CarPA high-positive subgroups (β = -0.50 vs. -0.52 at LS, and β = -0.37 vs. -0.30 at TH) suggested an independent association. Overall, these results support a contribution of anti-CarPA to systemic bone loss in EA patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorptiometry, Photon
  • Adult
  • Aged
  • Anti-Citrullinated Protein Antibodies / blood
  • Anti-Citrullinated Protein Antibodies / immunology
  • Antibodies, Anti-Idiotypic / blood
  • Antibodies, Anti-Idiotypic / immunology
  • Arthritis, Rheumatoid / complications
  • Arthritis, Rheumatoid / diagnostic imaging
  • Arthritis, Rheumatoid / physiopathology*
  • Autoantibodies / blood
  • Autoantibodies / immunology
  • Bone Density*
  • Bone Resorption / blood
  • Bone Resorption / complications
  • Bone Resorption / physiopathology*
  • Female
  • Humans
  • Lumbar Vertebrae / diagnostic imaging
  • Lumbar Vertebrae / physiopathology
  • Male
  • Metacarpophalangeal Joint / physiopathology
  • Middle Aged
  • Osteoclasts / immunology
  • Osteoclasts / pathology
  • Osteolysis / complications
  • Osteolysis / diagnostic imaging
  • Osteolysis / physiopathology*
  • Protein Carbamylation / immunology

Substances

  • Anti-Citrullinated Protein Antibodies
  • Antibodies, Anti-Idiotypic
  • Autoantibodies

Grants and funding

This work was supported by the Instituto de Salud Carlos III (Spain) through grants [PI14/01651 and RD16/0012/0014 to AG; PI14/00442 and RD16/0012/0011 to IG-A and PI12/01578 to SC]. These grants are partially financed by the European Regional Development Fund of the EU (FEDER). CR was supported by Ministerio de Educacion Cultura y Deporte (Spain) through a FPU pre-doctoral fellowship [FPU15/03434]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.