Israel Medical Association Journal

Background: Increased cardiovascular morbidity has become a leading cause of mortality in rheumatoid arthritis (RA). Tumor necrosis factor-alpha (TNFα) inhibitors may influence flow-mediated vasodilation (FMD) of the brachial artery, common carotid intima-media thickness (ccIMT) and arterial stiffness indicated by pulse-wave velocity (PWV) in RA.

Objectives: To assess the effects of adalimumab treatment on FMD[1], ccIMT[2] and PWV[3] in early RA[4].

Methods: Eight RA patients with a disease duration ≤ 1 year received 40 mg adalimumab subcutaneously every 2 weeks. Ultrasound was used to assess brachial FMD and ccIMT. PWV was determined by arteriograph. These parameters were correlated with C-reacive protein, vonWillebrand factor (vWF), immunoglobulin M (IgM)-rheumatoid factor (RF), anti-CCP levels and 28-joint Disease Activity Score (DAS28).

Results: Adalimumab therapy successfully ameliorated arthritis as it decreased CRP[5] levels (P = 0.04) and DAS28[6] (P < 0.0001). Endothelial function (FMD) improved in comparison to baseline (P < 0.05). ccIMT decreased after 24 weeks, indicating a mean 11.9% significant improvement (P = 0.002). Adalimumab relieved arterial stiffness (PWV) after 24 weeks. Although plasma vWF[7] levels decreased only non-significantly after 12 weeks of treatment, an inverse correlation was found between FMD and vWF (R = -0.643, P = 0.007). FMD also inversely correlated with CRP (R = -0.596, P = 0.015). CRP and vWF also correlated with each other (R = 0.598, P = 0.014). PWV and ccIMT showed a positive correlation (R = 0.735, P = 0.038).

Conclusions: Treatment with adalimumab exerted favorable effects on disease activity and endothelial dysfunction. It also ameliorated carotid atherosclerosis and arterial stiffness in patients with early RA. Early adalimumab therapy may have an important role in the prevention and management of vascular comorbidity in RA.

Background: The presence of anti-cyclic citrullinated peptide autoantibody is highly specific for rheumatoid arthritis. Certain HLA-DR4 (HLA-DRB1*04) alleles, also known as the "shared epitope," are associated with increased susceptibility to RA[1]. In addition, these alleles may also have relevance for disease outcome. Anti-CCP[2] antibody positivity has been associated with the presence of HLA-DR4 alleles in patients with RA. However, there is little information available regarding any relationship between quantitative anti-CCP production (serum anti-CCP concentrations) and the shared epitope.

Objectives: To determine the association between anti-CCP antibody production and various HLA-DRB1 alleles.

Methods: Serum anti-CCP, rheumatoid factor and C-reactive protein levels were assessed in 53 RA patients. All these patients underwent HLA-DRB1 genotyping.

Results: Of the 53 patients 33 (62%) were positive for anti-CCP antibody. We found significant correlations between anti-CCP and RF[3] positivity (chi-square = 6.717, P < 0.01), as well as between anti-CCP and HLA-DRB1*04 positivity (chi-square = 5.828, P < 0.01). There was no correlation between RF positivity and serum levels, CRP[4] serum levels and HLA-DRB1*04 positivity. When quantitatively comparing serum anti-CCP levels with shared epitope positivity, patients carrying one or two copies of HLA-DRB1*04 alleles had significantly higher anti-CCP concentrations (530.0 ± 182.6 U/ml) compared to DRB1*04-negative patients (56.8 ± 27.4 U/ml) (P < 0.01). There was no difference in serum anti-CCP antibody concentrations between patients carrying only one HLA-DRB1*01 allele but no HLA-DRB1*04 allele (12.0 ± 8.6 U/ml) in comparison to SE[5]-negative patients (76.8 ± 56.2 U/ml). Regarding non-SE HLA-DRB1 genotypes, all 6 patients (100%) carrying DRB1*15 alleles and 6 of 7 (85%) patients carrying DRB1*13 were anti-CCP positive. In addition, patients with HLA-DRB1*13 (282.5 ± 23.8 U/ml) and DRB1*15 (398.7 ± 76.2 U/ml) produced significantly more anti-CCP than did any other non-SE HLA-DRB1 subtypes (P < 0.01).

Conclusions: There is significant association between anti-CCP and RF, as well as between anti-CCP and SE positivity in RA. In addition, the presence of one or two copies of HLA-DRB1*04 alleles has been associated with higher serum anti-CCP antibody levels. Thus, patients carrying HLA-DRB1*04 alleles exhibited an overall tenfold increase in serum anti-CCP antibody levels in comparison to HLA-DRB1*04-negative subjects. Increased anti-CCP production may also be associated with other non-SE HLA-DRB1 genotypes, such as DRB1*13 or DRB1*15. In reports by other investigators, both anti-CCP concentrations