Session Title: Rheumatoid Arthritis - Human Etiology and Pathogenesis
Session Type: Abstract Submissions (ACR)
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.
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).
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.
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.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/rheumatoid-factor-isotypes-in-relation-to-antibodies-against-citrullinated-peptides-in-individuals-before-onset-of-rheumatoid-arthritis/