There is little evidence on prediction of clinical response to biologics in patients with RA. Recently, it has been suggested that clinical response to tumor necrosis factor (TNF) inhibitors was related to periodontal conditions, which might be affected by infection with Porphyromonas gingivalis (P.g.). Additionally, serum antibody responses to P. g were associated with RA and periodontitis.Newly established test of antibody against hemin binding protein 35 (HBP) of P.g., which has an ability specifically bind to P.g. containing protein HBP, can be available.
Objectives
To evaluate whether serum antibody responses to P.g. antigens and periodontal conditions are associated with clinical response to biologics in patients with RA.
Methods
20 patients with severe RA enrolled in this study were treated with biologics according to the usual regimen. Clinical background and disease parameters were assessed at entry. DAS28-CRP was evaluated at 6 months (reassessment) after the initiation of biologics. Periodontal conditions were also assessed at entry. Serum levels of antibodies against P.g. sonicated extracts (SE) and HBP of P.g. were determined by enzyme-linked immunsorbent assay, respectively.
Results
Their mean (SD) age was 57.2 (13.4) years. Patients were predominantly women (85%) with mean disease duration of 8.2 (6) years.10 patients were treated with TNF-i, 7 with IL-6 blocker and 3 with CTLA4-Ig, respectively. Most patients had active disease with DAS28-CRP 4.2 (0.9) at baseline, and showed an improvement of DAS28-CRP 2.87 (0.82) at reassessment. Seven patients (35%) achieved remission (DAS28-CRP <2.3) at reassessment. The mean serum levels of anti-CCP antibodies were 270.2 (221.9), and the mean serum levels of antibodies against P.g. SE and HBP were 15.9 (52.3) and 0.632 (0.276), respectively at baseline. Periodontal conditions of the patients were as follows; mean PD was 2.62 (0.51) (mm), mean CAL was 2.85 (0.77) (mm), mean PCR was 0.37 (0.23) (%), and mean BOP was 0.21 (0.17) (%) at baseline. No associations were observed between changes in DAS28-CRP (delta-DAS28-CRP) and serum and periodontal parameter values (serum levels of antibodies against P.g. SE and HBP, PD, CAL, PCR, and BOP). Antibody titers against P.g. SE gradually decreased, on the other hand, anti-P.g. HBP was increased during 6 months.
Conclusions
Antibodies titers against P.g. and periodontal conditions could not predict the responses to biologics, but further studies are required to evaluate this hypothesis. And to our knowledge, this is the first report describing the change of serum level of antibodies against P.g. after treatments with biologics except infliximab.
References
Savioli C. et al. J Clin Rheumatol. 4:180–184(2012) Okada M. et al. J Periodontol. 82:1433–1441(2011) tumor necrosis factor treatment response in rh a Rinaudo-Gaujous M. et al. Ann Rheum Dis. 72(S1):A42(2013) Shibata Y. et al. J Periodont Res. 46:673–681(2011) rthritis. J Clin Rheumatol. 4: 180–184 (2012)
Biological disease-modifying anti-rheumatic drugs (bDMARDs) against pathogenic proinflammatory cytokines and lymphocytes, such as tumour necrosis factor-α (TNF-α), interleukin-6, T cells and B cell...
Tocilizumab (TCZ), an inhibitor of interleukin-6 (IL-6), has been widely used to treat rheumatic diseases such as rheumatoid arthritis (RA) and juvenile idiopathic arthritis. Recently, TCZ was approved for use in patients with giant cell aortitis and Takayasu aortitis. However, TCZ treatment sometimes obscures changes in the conventional biomarkers for infection such as serum levels of C-reactive protein (CRP) and procalcitonin (PCT). Presepsin (P-SEP), a subtype of soluble CD14, has been recently identified as a biomarker for sepsis. In addition, we have reported the usefulness of P-SEP for the diagnosis of bacterial infection in RA patients because it is less affected by the disease activity.
Objectives
To examine the usefulness of P-SEP in RA patients complicated with bacterial infections during TCZ treatment.
Methods
In this study, 49 RA patients with bacterial infections (i+RA), 76 RA patients without bacterial infections (RA) and 23 healthy controls (HC) were enrolled. The presence of infection was strictly diagnosed by bacteriological examinations, typical clinical characteristics such as fever (38.0°C) and/or CRP elevation and/or increased white blood cell count, and improvements of these manifestations with antibiotics. Serum P-SEP levels were measured by an immunoassay. The CRP and PCT levels were measured simultaneously.
Results
The median serum P-SEP levels were 186.0 [interquartile range (IQR), 134.0–236.0], 691.0 [IQR, 345.5–842.0], 154.5 [IQR, 145.8–165.5] l, and 161.0 [IQR, 146.5–166.0] pg/mL for TCZ (n=25), i+TCZ (pre-antibacterial treatment; n=7), i+TCZ (post-antibacterial treatment; n=7) and the HC group, respectively. The P-SEP levels of the i+TCZ group were significantly elevated compared with those of the TCZ group (p<0.001). The i+TCZ group displayed elevated P-SEP levels despite normal CRP and PCT levels. After antibacterial treatment, P-SEP levels of the i+TCZ group were significantly decreased (p=0.016).
Conclusions
These results suggest that serum P-SEP levels are less affected by TCZ treatment compared with other conventional inflammatory biomarkers such as CRP and PCT. Moreover, P-SEP levels are useful for the assessment of bacterial infections in RA patients treated with TCZ.
Reference
[1] Tsuji S, et al. Mod Rheumatol2017;27(4):718–720.
A 66-year-old woman with symptoms of fatigue and headache was diagnosed with giant cell arteritis (GCA). Fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) revealed the strong accumulation of FDG in the descending aorta, abdominal aorta, bilateral subclavian artery, and total iliac artery. Diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) showed signal enhancement at the descending aorta and abdominal aorta. We repeated FDG-PET and DWIBS 2 months after the initiation of therapy with prednisolone. In line with the FDG-PET findings, the signal enhancement of the aortic wall completely vanished on DWIBS. DWIBS may be a novel useful tool for the diagnosis and follow-up of GCA treatment.
We report the case of a 40-year-old patient with systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) overlap syndrome with pulmonary arterial hypertension (overlap-PAH) that was successfully treated with a combination of immunosuppressive therapy and the soluble guanylate cyclase stimulator riociguat. She was diagnosed with mixed connective tissue disease (MCTD) two years prior to admission. She was admitted to our hospital with dyspnea on exertion and progressive skin sclerosis. She fulfilled both SLE and SSc classification criteria and was re-diagnosed with overlap syndrome. The tricuspid valve pressure gradient (TRPG) on echocardiography was 64 mmHg at admission. On right heart catheterization, mean pulmonary arterial pressure (mPAP) was 43 mmHg and pulmonary capillary wedge pressure was 15 mmHg. We diagnosed her with SSc-SLE overlap-PAH and started treatment with corticosteroids and intravenous cyclophosphamide. We also started treatment with riociguat because we speculated she had a component of SSc-PAH and that immunosuppressive therapy alone may be insufficient. We chose riociguat because of its favorable treatment effect on SSc-PAH. Two months after treatment, her TRPG improved to 33 mmHg and the skin sclerosis improved dramatically, suggesting the efficacy of multi-drug treatment and the importance of early intervention.
A 26-year-old woman with Takayasu's arteritis (TAK) experienced back and neck pain during tocilizumab (TCZ) treatment. The levels of C-reactive protein were normal, and ultrasonography revealed no significant changes. Diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) showed signal enhancement in the walls of several arteries. Contrast computed tomography showed arterial inflammation in the same lesion. After increasing the dose of prednisolone and TCZ, all signal enhancements decreased and continued to decrease, as observed on days 76 and 132. Thus, DWIBS may be a novel imaging modality for assessing the disease activity of TAK, particularly during follow-up.
