Opsonic and Antibody Responses to Pneumococcal Polysaccharide in Rheumatoid Arthritis Patients Receiving Golimumab Plus Methotrexate.

Vaccination against Streptococcus pneumoniae is recommended for rheumatoid arthritis (RA) patients receiving immunosuppressive treatments. The objective of this study was to evaluate the humoral response to 23-valent pneumococcal polysaccharide vaccination (PPSV23) in RA patients receiving methotrexate (MTX) alone or in combination with a tumor necrosis factor inhibitor, golimumab (GOM).PPSV23 was given to 114 RA patients, who were classified into three groups: RA control (n = 35), MTX alone (n = 55), and GOM + MTX (n = 24). Before and 4 to 6 weeks after vaccination, concentrations of antibodies against pneumococcal serotypes 6B and 23F were measured using an enzyme-linked immunosorbent assay and antibody functionality was determined using a multiplexed opsonophagocytic killing assay, reported as the opsonization index (OI).The IgG concentrations and OIs were both significantly increased in all treatment groups in response to PPSV23 vaccination. In the GOM + MTX group, the IgG responses were lower than those in the MTX alone or control groups, whereas the OI responses were similar to those in the other 2 groups. Furthermore, discrepancies between the IgG and OI responses were found in GOM + MTX group. No severe adverse effect was observed in any treatment groups.OI responses indicate that antibody functionality rather than antibody quantity is important. The similarity of these measurements between all 3 groups suggests that RA patients receiving MTX + GOM still benefit from receiving the PPSV23 vaccination, even though they produce less IgG in response to it. These results can help clinicians to better schedule and evaluate pneumococcal vaccination for RA patients.

The efficacy of mizoribine for the treatment of rheumatoid arthritis and its correlation with renal function.

OBJECTIVES: To evaluate the correlation between the efficacy of mizoribine (MZR) and the factors that might effect MZR concentration: renal function and dosage and administration of MZR in patients with rheumatoid arthritis (RA). METHODS: The efficacy of MZR treatment was prospectively evaluated in 97 RA regardless of dosage, at the 14 participated institutions. The Disease Activity Score 28-CRP3 was used to assess RA activity. The renal function was evaluated based on the serum creatinine and serum cystatin-C (Cys-C). The patients were followed up for 24 weeks. RESULTS: The patients with a mean age 66.2 years included 18 male. The renal function assessment showed increased creatinine in 16.4% of patients and increased Cys-C in 54.5%, suggesting the higher sensitivity of Cys-C to detect impaired renal function than creatinine. In patients with good or moderate response according to the European League against Rheumatism classification criteria, the Cys-C was significantly higher compared with those with no response. MZR treatment was significantly more effective in patients with an arithmetic product of the single MZR dose used and Cys-C of 179 or more. CONCLUSIONS: The efficacy of MZR may increase in proportion to its single dose, or increased Cys-C level in patients with impaired renal function.

Serum osteoprotegerin concentration is associated with carotid atherosclerotic plaque in patients with rheumatoid arthritis.

OBJECTIVE: Osteoprotegerin (OPG), a regulator of bone resorption, is involved in the pathogenesis of rheumatoid arthritis (RA) and atherosclerosis. OPG is elevated in patients with coronary artery disease, and high OPG levels are associated with cardiac disease severity and mortality in the general population. The purpose of this study was to investigate the relationship of serum OPG levels, traditional coronary risk factors, and RA-related factors to carotid atherosclerosis in RA patients. METHODS: Ninety-one RA patients were studied (85 % women, age 60 ± 10 years). Serum OPG levels were measured by an enzyme-linked immunosorbent assay. The prevalence of carotid plaque was assessed by ultrasonographic imaging in all patients. The relationship between various clinical characteristics, OPG, and carotid plaque was examined. RESULTS: Serum OPG levels were significantly higher in patients with carotid plaque than in those without plaque (median level 1,397 vs. 887 pg/mL, respectively; P = 0.006). There were no significant differences between RA patients with and without carotid plaque with respect to sex, duration of RA, blood pressure, body mass index, smoking, low-density lipoprotein cholesterol, Disease Activity Score-28, van der Heijde-modified Sharp score, and prednisolone dose. After adjusting for age, sex, and C-reactive protein, elevated levels of OPG were still associated with a higher prevalence of carotid plaque in patients with RA (P = 0.038). CONCLUSION: RA patients suffer from accelerated atherosclerosis and also have increased levels of OPG. The serum OPG level is independently associated with carotid plaque.

Analysis of cytokine production patterns of peripheral blood mononuclear cells from a rheumatoid arthritis patient successfully treated with rituximab.

We had a rheumatoid arthritis (RA) patient resistant to multiple drugs and who developed panniculitis due to etanercept treatment, then responded fairly well to rituximab. Intracellular staining of cytokines in the peripheral blood mononuclear cells before and after rituximab administration revealed that the cytokine production, representative of T-helper (Th)1-, Th2-, and Th17-type responses, decreased abruptly after the treatment. Interestingly, this timing coincided with that of the manifestation of the beneficial effect. This relationship may provide useful insight into the mechanism of action of the drug and hence about the pathogenesis of RA.

Vasculo-Behçet's disease with non-traumatic subcapsular hematoma of the kidney and aneurysmal dilatations of the celiac and superior mesenteric arteries.

We report a patient with vasculo-Behçet's disease treated successfully with a high dose of prednisolone. In 2002, the patient was diagnosed with vasculo-Behçet's disease. He was admitted to our hospital because of sudden-onset right lower back pain in June 2006. Upon admission, abdominal angiography revealed aneurysmal dilatations of the celiac and superior mesenteric arteries. He was treated promptly with high-dose prednisolone, after which the aneurysms displayed no further enlargement. As we believe this case to be quite rare, we report this case with a literature review in support of this characterization.

Recruitment of immature neutrophils in peripheral blood following leukocytapheresis therapy for rheumatoid arthritis.

The objective of this study is to evaluate the cellular mechanism underlying filtration leukocytapheresis (LCAP) therapy for the treatment of rheumatoid arthritis (RA). Thirteen patients with refractory RA each underwent three sessions of LCAP. Before (pre-) and after (post-) the completion of the first LCAP session, peripheral blood was sampled and analyzed for neutrophil surface markers using flow cytometry. The surface antigens of peripheral blood mononuclear cells (PBMCs) and neutrophils obtained at pre- and post-LCAP were then analyzed using a fluorescence-activated cell sorter. The American College of Rheumatology's criterion of a 20% improvement was achieved in six patients, but not in the other seven patients, after LCAP therapy. The post-LCAP number of blood band form neutrophils with a bone marrow phenotype (CD49d(dim+), low density) was higher among the responders than among the nonresponders, suggesting an association between the clinical response and the recruitment of bone-marrow-derived neutrophils. After the nonspecific absorption of WBCs during a 1-h Cellsorba procedure, the number of PBMCs was consistently decreased, although the number of neutrophils that were affected by removal plus recruitment varied in a manner that was independent of efficacy. In contrast, the emergence of immature neutrophils in the peripheral blood was characteristic of the effective therapies. These cells were found after the 1st session of responders and also found following sessions of LCAPs. Immature neutrophils, which may be recruited from the bone marrow in the peripheral blood after the first session of LCAP, can predict the clinical efficacy of subsequent LCAP sessions.

Rheumatoid arthritis fibroblast-like synoviocytes express BCMA and are stimulated by APRIL.

OBJECTIVE: Fibroblast-like synoviocytes (FLS) are among the principal effector cells in the pathogenesis of rheumatoid arthritis (RA). This study was undertaken to examine the variety of stimulating effects of APRIL and its specific effect on FLS in the affected RA synovium. METHODS: Synovium and serum samples were obtained from patients with RA, patients with osteoarthritis (OA), and healthy subjects. Soluble APRIL proteins were assayed by enzyme-linked immunosorbent assay. The relative gene expression of APRIL, BCMA, interleukin-6 (IL-6), tumor necrosis factor alpha (TNFalpha), IL-1beta, and RANKL was assessed in RA and OA FLS by polymerase chain reaction. Effects of APRIL on the production of proinflammatory cytokines and RANKL in RA FLS were investigated by flow cytometry and with the use of a BCMA-Fc fusion protein. RESULTS: A significantly higher level of soluble APRIL was detected in RA serum compared with normal serum. Among the 3 receptors of APRIL tested, RA FLS expressed only BCMA, whereas OA FLS expressed none of the receptors. APRIL stimulated RA FLS, but not OA FLS, to produce IL-6, TNFalpha, IL-1beta, and APRIL itself. In addition, APRIL increased RA FLS expression of RANKL and also enhanced progression of the cell cycle of RA FLS. Neutralization of APRIL by the BCMA-Fc fusion protein attenuated all of these stimulating effects of APRIL on RA FLS. CONCLUSION: RA FLS are stimulated by APRIL and express the APRIL receptor BCMA. These results provide evidence that APRIL is one of the main regulators in the pathogenesis of RA.

From perception to sentence comprehension: the convergence of auditory and visual information of language in the left inferior frontal cortex.

We used functional magnetic resonance imaging (fMRI) to characterize cortical activation associated with sentence processing, thereby elucidating where in the brain auditory and visual inputs of words converge during sentence comprehension. Within one scanning session, subjects performed three types of tasks with different linguistic components from perception to sentence comprehension: nonword (N(AV); auditory and visual), phrase (P; either auditory or visual), and sentence (S; either auditory or visual) tasks. In a comparison of the P and N(AV) tasks, the angular and supramarginal gyri showed bilateral activation, whereas the inferior and middle frontal gyri showed left-lateralized activation. A comparison of the S and P tasks, together with a conjunction analysis, revealed a ventral region of the left inferior frontal gyrus (F3t/F3O), which was sentence-processing selective and modality-independent. These results unequivocally demonstrated that the left F3t/F3O is involved in the selection and integration of semantic information that are separable from lexico-semantic processing.