IgA rheumatoid factor is associated with bone mineral density preservation in rheumatoid arthritis

Clin Rheumatol. 2021 Dec;40(12):4879-4887. doi: 10.1007/s10067-021-05814-4. Epub 2021 Jul 20.


Introduction: Autoantibodies such as IgM rheumatoid factor (RF) and anti-citrullinated proteins/peptides antibodies (ACPA) have previously been incriminated in systemic bone loss in rheumatoid arthritis (RA). There are, however, no data describing association of IgA RF and IgG RF with systemic bone loss.

Objective: This study was aimed to investigate the association of RF isotypes with systemic bone loss among patients with RA.

Methods: RF isotypes and ACPA were measured by enzyme-linked immunosorbent assay among 153 patients with RA. Bone mineral density (BMD) was assessed using dual-energy X-ray absorptiometry.

Results: Ninety-four (61.4%) patients had positive IgA RF, 89 (58.2%) had positive IgG RF, 109 (71.2%) had positive IgM RF, whereas 122 (80.3%) RA patients tested positive for ACPA. Compared to the IgA RF-negative patients, IgA RF-positive patients exhibited higher disease activity and had higher RF titers. Seven (4.6%) patients had low BMD at femoral neck, 12 (7.8%) at total femur, and 47 (30.7%) at lumbar spine. IgA RF was found to be associated with protection against low BMD at spine (OR = 0.47, 95% CI = 0.23-0.95, p = 0.034). This association was further confirmed in the multivariate regression analysis taking into account several potential confounding factors (OR = 0.21, 95% CI = 0.06-0.65, p = 0.039). No association between low BMD and the presence of IgG RF or IgM RF or ACPA was found.

Conclusion: IgA RF for the first time ever was shown to be associated with BMD preservation at spine in RA. Key points • IgA RF was associated with protection against low spinal BMD. • No association between low BMD and the presence of IgG RF or IgM RF was found.

Keywords: Anti-cyclic citrullinated proteins/peptides antibodies; Bone mineral density; IgA rheumatoid factor; IgG rheumatoid factor; IgM rheumatoid factor; Rheumatoid arthritis.

MeSH terms

  • Anti-Citrullinated Protein Antibodies
  • Arthritis, Rheumatoid*
  • Bone Density
  • Humans
  • Immunoglobulin A
  • Rheumatoid Factor*


  • Anti-Citrullinated Protein Antibodies
  • Immunoglobulin A
  • Rheumatoid Factor