Byeongzu Ghang

Neutrophil-to-lymphocyte ratio is a reliable marker of treatment response in rheumatoid arthritis patients during tocilizumab therapy

Abstract Objective: To investigate the reliable markers reflecting treatment response better than the traditional inflammatory indices in patients with rheumatoid arthritis (RA) receiving tocilizumab therapy. Methods: A total of 58 RA patients treated with tocilizumab for more than six months from January 2013 to December 2014 were initially included. Flares were defined as events that required steroid dose escalation, intra-articular steroid injections, or switching tocilizumab to other biologic agents. The clinical and laboratory data were retrospectively collected from electronic medical records. Results: Of the 52 patients except for six patients who were excluded, 16 experienced flares, and 36 were stable during tocilizumab therapy. The C-reactive protein (CRP) level did not significantly differ between a stable state before flares and at flares. Compared with those at the preflare time point, erythrocyte sedimentation rate (ESR), and neutrophil to lymphocyte ratio (NLR) were significantly higher at flares; however, ESR levels (n = 9) were within the normal limit or decreased (n = 4) at flares. Interestingly, NLR increased at flares in all but one patient in the flare group. Conclusion: NLR is a more reliable marker than ESR or CRP for evaluating the disease activity in patients with RA during tocilizumab therapy.

Longterm Outcomes of Renal Artery Involvement in Takayasu Arteritis

Objective. Takayasu arteritis (TA) involving the renal artery can result in hypertension (HTN), renal dysfunction, and premature death. The aim of this study was to investigate the longterm outcomes and factors that predict outcomes in patients with TA with renal artery stenosis. Methods. The medical records of patients diagnosed with TA between January 1997 and December 2014 were reviewed retrospectively. Renal artery involvement was based on computed tomography and/or angiography findings. Poor outcome was defined as refractory HTN, chronic renal insufficiency, or death. Results. Of the 62 TA patients with renal artery involvement, 11 (17.7%) underwent renal artery revascularization. Younger age, male sex, and more severe stenosis (> 70%) were associated with vascular intervention. After a median followup of 90.6 months, 11 (17.7%) of the 62 patients had refractory HTN and 6 (9.7%) had chronic renal insufficiency. Renal insufficiency [5/15 (33.3%) vs 3/47 (6.4%), p = 0.016] and bilateral involvement [12/15 (80.0%) vs 23/47 (48.9%), p = 0.041] were significantly more frequent in patients with poor than good outcomes. Multivariate Cox analysis revealed that renal insufficiency at presentation (HR 13.778, 95% CI 3.530–53.786, p < 0.001) and bilateral renal artery involvement (HR 5.053, 95% CI 1.179–21.661, p = 0.029) were significant risk factors for poor outcomes at followup, but performance of revascularization procedure was not (HR 0.663, 95% CI 0.176–2.498, p = 0.543). Conclusion. Bilateral lesions and renal functional impairment at presentation, but not implementation of revascularization procedures, were significant factors for outcomes in TA patients with renal artery involvement.

Nontuberculous mycobacterial infection in rheumatoid arthritis patients: a single-center experience in South Korea

Background/Aims Nontuberculous mycobacteria (NTM) infection has been increasing worldwide in both general population and immunocompromised patients, which has also been reported in rheumatoid arthritis (RA) patients. This study aimed to identify the incidence and clinical characteristics of NTM infection in RA patients living in tuberculosis (TB) infection endemic area. Methods We performed a retrospective analysis of NTM infection cases in our RA registry at a tertiary referral center from January 1995 to December 2013. The clinical features of them were compared to those of 52 TB infection patients from same registry. Results Among 1,397 patients with RA, NTM infection was newly developed in 26 patients and the incidence of NTM infection was 164.8 per 100,000 patient-years. The Mycobacterium avium complex was the most frequent isolate (76.9%). None of the NTM infections had extrapulmonary involvement, which was rather common in TB infection (26.9%). Patients with NTM infection were older, received higher cumulative steroid doses, and had higher rates of past TB infection history and concomitant interstitial lung disease (ILD) than cases with TB infection. Conclusions In South Korea, NTM infection is not rare in RA patients, and infection rates are growing. Physicians should be cautious about NTM infection in patients with a history of TB infection or concomitant ILD, even living in TB endemic area.

CD14+ Cells with the Phenotype of Infiltrated Monocytes Consist of Distinct Populations Characterized by Anti-inflammatory as well as Pro-inflammatory Activity in Gouty Arthritis

It has been suggested that inflammasome-mediated IL-1β production in monocytic cells is responsible for the acute inflammatory response in gouty arthritis. However, phenotypical and functional analyses of monocytes during gouty arthritis have yet to be conducted. Therefore, we investigated the characteristics of monocytes/macrophages in the synovial fluid cells of patients with acute gout. The number and frequency of monocytes/macrophages in the synovial fluid mononuclear cells (SFMCs) of patients was examined. The expression of markers for monocyte recruitment and tissue-resident macrophages, the production of pro-inflammatory and anti-inflammatory cytokines, and phagocytosis were analyzed in the monocytes/macrophages of patients with acute gout attacks. The number and frequency of CD14+CD3−CD19−CD56− monocytes/macrophages was markedly increased in the SFMCs of patients with gout compared to those of patients with rheumatoid arthritis (RA). CD14+ cells showed the phenotypes of infiltrated monocytes rather than tissue-resident macrophages, characterized by a high expression of CCR2, MRP8, and MRP14, but a low expression of MERTK and 25F9. These cells had the capacity to produce pro-inflammatory cytokines such as TNF-α and IL-1β after stimulation with lipopolysaccharides. In addition, anti-inflammatory features, including CD163 expression and IL-10 production from CD14+ cells, were significantly higher in patients with gout than in those with RA. CD14+ cells with phenotype of M2 macrophages had high phagocytic activity for monosodium urate crystals. Thus, our results indicate that monocytes/macrophages from patients with gout have the phenotype of infiltrated monocytes, and these cells consist of different populations characterized by anti-inflammatory activities as well as pro-inflammatory functions.

Clinical features and prognoses of acute transverse myelitis in patients with systemic lupus erythematosus

Background/Aims Acute transverse myelitis (ATM) is a severe complication of systemic lupus erythematosus (SLE). This study evaluated the clinical factors related to outcome in patients with SLE-associated ATM. Methods The medical records of patients diagnosed with SLE-associated ATM between January 1995 and January 2015 were reviewed. The patients were divided into two groups based on improvement of neurological deficits after treatment: favorable response group and unfavorable response group. During follow-up, the recurrence of ATM was also analyzed. Results ATM was identified in 16 patients with SLE. All of the patients were treated with high doses of methylprednisolone (≥ 1 mg/kg daily). Although 12 patients (75%) recovered (favorable response group), four (25%) had persistent neurologic deficits (unfavorable response group) after the treatment. Compared to the favorable response group, significantly higher Systemic Lupus Erythematosus Disease Activity Index-2000, lower complement levels and initial severe neurologic deficits were found in the unfavorable response group. Among the 12 favorable response patients, five (41.7%) experienced recurrence of ATM during the followup. Patients (n = 5) who experienced relapse had a shorter duration of high-dose corticosteroid treatment (13.2 days vs. 32.9 days, p = 0.01) compared to patients who did not relapse. The mean duration of tapering-off the corticosteroid until 10 mg per day was significantly longer in non-relapse group (151.3 ± 60.8 days) than in relapse group (63.6 ± 39.4 days, p = 0.013). Conclusions Higher disease activity in SLE and initial severe neurologic deficits might be associated with the poor outcome of ATM. Corticosteroid slowly tapering-off therapy might be helpful in preventing the recurrence of ATM.

Predicting eventual development of lupus nephritis at the time of diagnosis of systemic lupus erythematosus

OBJECTIVES To investigate factors predictive of future lupus nephritis development when systemic lupus erythematosus (SLE) is diagnosed. METHODS Patients with newly diagnosed SLE without renal manifestations were followed for development of lupus nephritis, comparing findings at baseline between those who did or did not develop nephritis. Albumin-to-globulin ratio (AGR) was calculated as albumin/(total protein-albumin). Cox proportional hazard model was used to identify predictors of lupus nephritis. RESULTS Of 278 patients, 241 did not and 37 did develop lupus nephritis during follow-up. On univariate analysis, young age, low C3, low C4, high anti-dsDNA titre, anti-Sm antibody, anti-RNP antibody and low AGR were associated with a higher risk of lupus nephritis. On multivariate analysis, factors predictive of nephritis were age [adjusted hazard ratio (aHR) 0.928, 95% confidence interval (CI): 0.895-0.961, p < 0.001], C3 (aHR 0.977, 95% CI: 0.966-0.989, p < 0.001), anti-dsDNA titre (aHR 1.004, 95% CI: 1.000-1.007, p = 0.026) and anti-Sm antibody (aHR 2.097, 95% CI: 1.040-4.229, p = 0.038). In particular, a low AGR (aHR 4.972, 95% CI: 2.394-10.326, p < 0.001) was strongly associated with an increased risk of future lupus nephritis development. CONCLUSION Young age, low C3, high anti-dsDNA titre and presence of anti-Sm antibody at diagnosis of SLE were associated with a risk of future lupus nephritis, but the hazard was greatest with a low AGR value, suggesting that a greater proportion of immunoglobulin relative to total protein is associated with the development of nephritis.

AB0185 Undercarboxylated Osteocalcin as A Marker for Metabolic Dysfunction in Patients with Rheumatoid Arthritis

Background Osteocalcin (OC) has been known as one of bone-forming markers and the serum level in rheumatoid arthritis (RA) patients was usually lower than that in healthy control. Serum OC, secreted from osteoblasts, exists in either carboxylated OC (cOC, major form) or undercarboxylated OC (ucOC, minor form). Different to the osteogenic role of cOC, ucOC has been suggested to be involved in energy metabolism. Recent studies have shown that significantly lower concentration of ucOC in the blood was associated with metabolic derangement including insulin resistance. Therefore, we would like to investigate whether level of ucOC in RA patients decreased and it was accompanied by metabolic dysregulation, which has never been studied before. Objectives To determine the association between ucOC and metabolic alteration including insulin resistance in patients with RA Methods Clinical information of patients and healthy volunteers was collected from electronic data base of single center registry. The concentrations of cOC and ucOC were measured in the sera from established RA patients (n=30) and healthy subjects (n=13) by enzyme-linked immunosorbent assay (ELISA). Various metabolic parameters, including insulin concentration, homeostasis model assessment of insulin resistance (HOMA-IR) and body mass index (BMI), were measured and analyzed. Results The concentration of cOC in blood was not significantly different between RA patients (13.49±2.97 ng/mL) and healthy controls (14.45±2.48 ng/mL). However, the concentration of ucOC was significantly lower in the sera of patients with RA (3.29±2.36 ng/mL) than in those of healthy individuals (5.94±2.75 ng/mL, p=0.003). Intriguingly, ucOC levels have been found to be positively associated with parameters of metabolic derangement including insulin levels, HOMA-IR and BMI (Figure 1). These associations were not found in healthy controls.Figure 1. Positive correlation between the levels of ucOC and the values of insulin (left), HOMA-IR (middle), and BMI (right) in the sera of RA patients. Conclusions The present study show that the concentration of ucOC, but not cOC was significantly lower in patients with RA, and its value was positively correlated with insulin resistance. Therefore, ucOC can be supposed to have a unique role in metabolic dysregulation in RA. Disclosure of Interest None declared