ObjectivesActive immunization, or vaccination, with tumor necrosis factor (TNF)-Kinoid (TNF-K) is a novel approach to induce polyclonal anti-TNF antibodies in immune-mediated inflammatory diseases. This study was performed to transfer the proof of concept obtained in mice model of rheumatoid arthritis (RA) into human. We designed a pilot study to demonstrate the feasibility of therapeutic vaccination in RA.MethodsThis was a phase IIa, placebo-controlled, multicenter study in adults with RA who previously experienced secondary failure of TNF antagonists. Patients were immunized intramuscularly with 2 or 3 doses of placebo (n = 10) or 90 (n = 6), 180 (n = 12), or 360 µg TNF-K (n = 12). The primary objective was to identify the best dose and schedule based on anti-TNF antibody titers. Clinical symptoms and safety were assessed during 12 months and solicited reactions for 7 days after each injection.ResultsThe highest anti-TNF antibody response was detected in patients immunized with 360 µg TNF-K and with 3 injections, although this difference was not significant with all other groups. Similar proportions of patients receiving TNF-K and placebo reported adverse events up to month 12. Serious adverse events were reported by 4 patients treated with TNF-K (13.3%) and 3 treated with placebo (30.0%), all unrelated to treatment. At month 12, DAS28-CRP, tender and swollen joint counts, and HAQ scores decreased significantly more in patients who exhibited anti-TNF antibody response than in patients who did not.ConclusionsTNF-K therapeutic vaccination induced dose- and schedule-dependent anti-TNF antibodies in RA patients and was well tolerated. Patients who developed anti-TNF antibodies showed a trend toward clinical improvement. Although the most aggressive dose and schedule, i.e. 360 mg dose administered 3 times, did show a strong trend of higher antibody response, further studies are warranted to examine even higher and more frequent doses in order to establish the best conditions for clinical improvement.Trial RegistrationClinicalTrials.gov NCT01040715

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Objective. In this study, we compare the prevalence of HT in RA and OA patients, exposed to high-and low-grade chronic inflammation, respectively , to assess the possible association between chronic inflammation and HT. Methods.A total of consecutive 627 RA and 352 OA patients were enrolled in this multicentric study. HT was defined as a systolic blood pressure (BP) ≥140 and/or diastolic BP ≥90 mmHg or current use of any antihypertensive drug. Overweight/obesity was defined as body mass index (BMI) ≥25, and patients ≥65 years old were considered elderly.Results. The prevalence of HT was higher in the OA group than in the RA group [73.3% (95%CI 68.4, 77.7) and 59.5% (95%CI 55.6, 68.4) P<0.001 respectively]. When the results were adjusted for age and BMI the HT prevalence was similar in both groups [RA 59%(95%CI 55.1, 63.8) OA 60%(95%CI 58.4, 65.0)]. In both groups, the prevalence of HT was higher in the elderly and those who were overweight than in the younger patients and those with a BMI <25 .Overweight (BMI ≥25) and age ≥65 were independent predictors of HT in multivariate logistic regression model, which show no association of HT and the disease (RA or OA). Conclusion.The results indicated a robust association of age and BMI with HT prevalence in both RA and OA. The difference in HT prevalence between RA and OA is rather due to age and BMI then to features of the disease, putting into question specific association of HT with RA.

The objective of the present study was to investigate possible changes in granulysin (GNLY)-mediated cytotoxicity of peripheral blood lymphocytes in psoriatic arthritis (PsA) patients with respect to different phases of the disease. We prospectively enrolled 25 PsA patients in the active phase, 26 PsA patients in remission and 24 healthy controls. The simultaneous detection of intracellular GNLY and cell surface antigens (CD3 and CD56) was performed with flow cytometry. GNLY apoptotic protein was visualised by immunocytochemistry. Natural killer (NK) cell cytotoxicity was analysed with a cytotoxicity assay against human erythroleukaemia K-562 cells. The percentage of GNLY(+) cells did not differ significantly between PsA patients in the acute phase and those in remission; however, it was always higher than in healthy examinees due to the increased percentage of GNLY(+) cells within T cells, NKT cells, and both, and in the CD56(+dim) and CD56(+bright) NK subsets. The mean fluorescence intensity for GNLY was higher in all lymphocyte subpopulations in the acute phase than in remission and in healthy controls. Accordingly, GNLY-mediated NK cell cytotoxicity against K-562 cells of active phase PsA patients was significantly higher than that in patients in remission or in healthy controls. These findings demonstrated the involvement of GNLY in the worsening of PsA and suggested that GNLY mediated the development of joint lesions.

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