ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 447

Rheumatoid Factor Isotypes in Relation to Antibodies Against Citrullinated Peptides in Individuals before Onset of Rheumatoid Arthritis

Mikael Brink1, Monika Hansson2, Linda Mathsson-Alm3, Johan Rönnelid3, Lars Klareskog2 and Solbritt Rantapää-Dahlqvist4, 1Public Health & Clinical Medicine/Rheumatology, Umeå University, Umeå, Sweden, 2Department of Medicine, Rheumatology Unit, Karolinska Institute, Stockholm, Sweden, 3Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden, 4Public Health & Clinical Medicine/Rheumatology, Institution of Public health and clinical medicine/ Rheumatology, University of Umeå, Rheumatology, Sweden, Umeå, Sweden

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: ,

Session Information

Title: Rheumatoid Arthritis - Human Etiology and Pathogenesis

Session Type: Abstract Submissions (ACR)

Background/Purpose

The presence of rheumatoid factor (RF) and antibodies against citrullinated peptides (ACPA) has been shown to precede the development of rheumatoid arthritis (RA) by several years. The relationships between the separate antibody development of RF and ACPAs are unclear.

Methods

Three isotypes (IgA, IgG and IgM) of RF has been analyzed in samples from 333 pre-symptomatic individuals (contributing with 596 samples), who subsequently developed RA and 495 population controls, all donors to the Biobank of Northern Sweden. The pre-symptomatic samples were collected in median 6.1 (IQR 7.1) years before symptom onset. Cut-offs for RF isotypes were set at 95% specificity using ROC-curves. Data from the RF-isotypes were compared against ten ACPA specificities previously analyzed on a microarray based on the ImmunoCAP ISAC system (Phadia). RF isotypes were analyzed using the EliA on the ImmunoCAP 2500-system (Phadia).

Results

The frequency of RF isotypes in pre-symptomatic individuals were 25.7% for IgA, 17.6% for IgG and 26.7% for IgM, significantly more prevalent compared with controls (p<0.0001). The concentrations for each isotype increased gradually the closer to onset of symptoms the sample was collected.
All three isotypes were associated with smoking (Odds ratio (OR) IgA= 2.5 (95%CI 1.8-3.6), IgG 2.1 (1.4-3.2) and IgM 2.4 (1.7-3.4), respectively) but not with HLA-SE or PTPN22 T-variant. The combinations of each of the RF isotypes with ACPA specificities (a-Enolase (CEP-1/Eno5-21), fibrinogen (Fib)ß36-52, Fibα591, filaggrin (CCP-1/Fil307-324), vimentin ((Vim) 60-75 or Vim2-17) were associated with significantly shorter time to onset of symptoms (p<0.001-0.05). The OR (95%CI) for disease development in IgA, IgG and IgM positive individuals were in combination with Fib36-52, CEP-1 or Fil307-324 further increased from 7.1 (4.5-11.2), 4.5 (2.8-7.3) and 7.4 (4.7-11.7), respectively to OR= 12.5-19.6 for IgA, 7.5-16.2 for IgG and 17.4-20.7 for IgM.

Conclusion

RF isotypes predicted development of RA and in particular using combinations of both ACPAs and RF isotypes the association with disease development was high and the predating time shorter.

Disclosure:

M. Brink,
None;

M. Hansson,
None;

L. Mathsson-Alm,
None;

J. Rönnelid,
None;

L. Klareskog,
None;

S. Rantapää-Dahlqvist,
None.

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