IntroductionPatients with rheumatoid arthritis (RA) treated with abatacept (ABT) are at increased risk for vaccine-preventable infections. The aim of the present study is to evaluate the humoral response to 23-valent pneumococcal polysaccharide (PPSV23) vaccination in RA patients receiving ABT.MethodsThe immunogenicity study was nested within a randomized, double-blind placebo-controlled study, designed to evaluate the efficacy of the PPSV23. PPSV23 was given to 111 RA patients, who were classified into three groups: RA control (n = 35), methotrexate (MTX) alone (n = 55), and ABT (n = 21). Before and 4–6 weeks after vaccination, we measured the patients’ concentrations of antibodies against pneumococcal serotypes 6B and 23F using an enzyme-linked immunosorbent assay and determined their antibody functionality using a multiplexed opsonophagocytic killing assay, reported as the opsonization index (OI).ResultsThe pneumococcal serotype-specific IgG concentrations and OIs were both significantly increased in all treatment groups in response to PPSV23 vaccination. In the ABT group, the IgG responses for the 6B serotype were lower compared with those in the MTX alone or control groups, whereas the OI responses were similar to those in the other two groups. In a subgroup analysis, the pneumococcal serotype-specific IgG responses were significantly lower in both serotypes (6B and 23F) in the ABT/MTX group; however, the OI responses in the ABT group were not different from the control group. There was no association between the pneumococcal serotype-specific IgG and OI responses for the 6B serotype in patients receiving ABT in contrast to the control or MTX alone patients. No severe adverse effects were observed in any of the treatment groups.ConclusionsOI responses indicate antibody functionality rather than simply their amount, so the similarity of these measurements between all three groups suggests that RA patients receiving ABT still benefit from receiving the PPSV23 vaccination, even though they produce less IgG in response to it. The results suggest an influence of ABT on the humoral response to PPSV23 vaccination under MTX treatment; however, preserved opsonin responses are expected in RA patients treated with ABT plus MTX.Trial registrationUniversity Hospital Medical Information Network Clinical Trials Registry: UMIN000009566. Registered 12 December 2012.
The arterial supply of 100 human cadaver feet (87 cadavers) was investigated by stereoscopic arteriography and was compared phylogenetically to that of the macaque foot. The deep plantar arch was always well developed and complete, whereas the superficial plantar arch was usually slender and incomplete. The first proximal perforating artery arising from the dorsalis pedis artery formed the main component of the deep plantar arch in 82% of the feet. The second proximal perforating artery arising from the dorsal rete contributed to the deep plantar arch in 43% of the feet, and formed most of the arch in one foot. The dorsal rete was classified into four groups of variants based on the arterial source of the second dorsal metatarsal artery. These were the arcuate artery (25%), distal lateral tarsal artery (12%), proximal lateral tarsal artery (6%), and nondorsal rete (57%) variants. In the first intermetatarsal space, the dorsal and plantar metatarsal arteries shared a common trunk in 54% of the feet, but this did not occur in the other intermetatarsal spaces. The second dorsal metatarsal artery arose from the dorsal rete in 43% of the feet, and this artery was quite large, sometimes being the largest of all the dorsal and plantar metatarsal arteries. Variations of the arterial supply found in humans sometimes resembled the typical pattern found in the macaque.
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.
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