Effect of interleukin-6 receptor blockade on the balance between regulatory T cells and T helper type 17 cells in rheumatoid arthritis patients.

A new paradigm has emerged relating the pathogenesis of rheumatoid arthritis (RA), focused on the balance between T helper type 17 cells and regulatory T cells (T(regs) ). In humans, both subpopulations depend on transforming growth factor (TGF)-ß for their induction, but in the presence of inflammatory cytokines, such as interleukin (IL)-6, the generation of Th17 is favoured. Tocilizumab is a therapeutic antibody targeting the IL-6 receptor (IL-6R), which has demonstrated encouraging results in RA. The aim of this study was to evaluate the effect of tocilizumab on Th1 cells, Th17 cells, IL-17 and interferon (IFN)-γ double secretors Th17/Th1 cells, and T(regs) in RA patients. Eight RA patients received tocilizumab monthly for 24 weeks and blood samples were obtained every 8 weeks to study T cell populations by flow cytometry. The frequency of Th17 cells, Th1 cells and Th17/Th1 cells was evaluated in peripheral blood mononuclear cells (PBMCs) activated in vitro with a polyclonal stimulus. T(regs) were identified by their expression of forkhead box protein 3 (FoxP3) and CD25 by direct staining of PBMCs. Although no changes were detected in the frequency of Th1 or Th17 cells, the percentages of peripheral T(regs) increased after therapy. In addition, the infrequent Th17/Th1 subpopulation showed a significant increment in tocilizumab-treated patients. In conclusion, tocilizumab was able to skew the balance between Th17 cells and T(regs) towards a more protective status, which may contribute to the clinical improvement observed in RA patients.

Basal anti-cyclic citrullinated peptide (anti-CCP) antibody levels and a decrease in anti-CCP titres are associated with clinical response to adalimumab in rheumatoid arthritis.

OBJECTIVE: To investigate the effect of adalimumab treatment on anti-cyclic citrullinated peptide antibodies (anti-CCP) in patients with rheumatoid arthritis (RA). METHODS: 70 RA patients who failed treatment with disease modifying antirheumatic drugs (DMARDs) received 40 mg adalimumab subcutaneously every other week during 24 weeks. Serum samples were collected at baseline and at weeks 8, 16 and 24 before the corresponding adalimumab dose. The serum anti-CCP levels were tested by enzyme linked immunosorbent assay. RESULTS: At baseline, 52 of the 70 patients (74.3%) were positive for anti-CCP antibodies. 60 % of the anti CCP positive patients and 44.4% of the anti CCP negative patients were ACR 20 responders at week 24 (p<0.049). The serum levels of anti-CCP antibodies decreased significantly after 24 weeks of adalimumab treatment only in those patients who met ACR 20 response criteria at week 24 (p<0.00044). Differences between baseline anti-CCP titers and those at 8, 16 and 24 weeks were all statistically significant (p<0.014, 0.003 and 0.019 respectively). No statistically significant changes in the anti-CCP levels were observed in patients who did not meet the ACR 20 response criteria. CONCLUSION: Basal anti-CCP antibodies levels correlate with clinical response to adalimumab. A decrease in anti-CCP levels on time was observed in patients showing also clinical improvement, suggesting that serum anti-CCP antibodies determination may be useful in assessing treatment efficacy in RA patients.

Systemic vasculitis associated with Fasciola hepatica infection.

We report the case of a 50-year-old man who presented with systemic vasculitis associated with Fasciola hepatica infection. The patient presented with severe skin, kidney, spleen, ophthalmic, and neurological compromise. An immunological examination for primary vasculitis was negative and other infections were discounted by microbiological and serological analyses. The patient was treated with steroids without clinical response. The Fasciola hepatica infection was confirmed by the presence of specific immunoglobulin G (IgG) serum antibodies detected by a quantitative enzyme-linked immunosorbent assay (ELISA) with an optical density (OD) of 0.483 OD units (normal value<0.170 OD units) and a high-titre complement fixation (1/80 dilution). The patient received treatment with triclabendazole and all symptoms and systemic manifestations resolved within weeks. Hence, this previously unreported vasculitis-associated infection, if identified opportunely, can be treated and cured.

Tumour necrosis factor (TNF)alpha -308 G/G promoter polymorphism and TNFalpha levels correlate with a better response to adalimumab in patients with rheumatoid arthritis.

OBJECTIVE: To investigate the influence of -308 tumour necrosis factor-alpha (TNFalpha) promoter polymorphism and circulating TNFalpha levels in the clinical response to adalimumab treatment in patients with rheumatoid arthritis (RA). METHODS: Eighty-one patients with active RA were genotyped for the -308 TNFalpha polymorphism by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis and subdivided into two groups for each polymorphism (G/A and G/G genotype). All received 40 mg of adalimumab subcutaneously every other week. We compared the groups' clinical responses to adalimumab at 8, 16, and 24 weeks using the Disease Activity Score in 28 joints (DAS28). RESULTS: Both groups showed a significant improvement from baseline. A significant difference between groups was found at week 24. We found that 88.2% of G/G versus 68.4% of G/A for the -308 polymorphism were DAS28 responders (p = 0.05). The score improvement at week 24 was 2.5 +/- 1.3 in the G/G group and 1.8 +/- 1.3 in the G/A group for the -308 polymorphism (p = 0.04). The median of serum TNFalpha levels of the G/A group were lower than those of the G/G group, and statistically different at weeks 8 and 24 (p < 0.039 and p < 0.043). When comparing baseline levels to those achieved at 8, 16, and 24 weeks for the whole group, only responder patients showed a statistically significant overall increase in TNFalpha over time (p < 0.000001). CONCLUSION: A relationship between DAS28 improvement, the -308 G/G polymorphism, and increased circulating TNFalpha levels was found in Chilean RA patients treated with adalimumab.