Association between SYVN1 and SEL1 genetic polymorphisms and remission in rheumatoid arthritis patients treated with TNF-α inhibitors: a machine learning approach.

Rheumatoid arthritis (RA) is a severe chronic inflammatory condition that affects joint synovium. Suppressor/enhancer of lin-12-like (SEL1L)-Synoviolin 1 (SYVN1)-mediated endoplasmic reticulum-associated degradation (ERAD) is highly associated with RA development. Although targeting SEL1L-SYVN1-mediated ERAD can be beneficial, studies that evaluate the association between polymorphisms in their genes and remission from the disease in RA patients taking tumor necrosis factor (TNF)-α inhibitors have yet to be carried out. Hence, the purpose of this study was to investigate the association between SYVN1 and SEL1L polymorphisms and TNF-α inhibitor response using various machine learning models. A total of 12 single-nucleotide polymorphisms (SNPs), including 5 SNPs in SYVN1 and 7 SNPs of SEL1L were investigated. Logistic regression analysis was used to examine the relationship between genetic polymorphisms and response to treatment. Various machine learning methods were employed to evaluate factors associated with remission in patients receiving TNF-α inhibitors. After adjusting for covariates, we found that sulfasalazine and rs2025214 in SEL1L increase the remission rates by approximately 3.3 and 2.8 times, respectively (95% confidence intervals 1.126-9.695 and 1.074-7.358, respectively). Machine learning approaches showed acceptable prediction estimates for remission in RA patients receiving TNF-α inhibitors, with the area under the receiver-operating curve (AUROC) values ranging from 0.60 to 0.65. A polymorphism of the SEL1L gene (rs2025214) and sulfasalazine were found to be associated with treatment response in RA patients receiving TNF-α inhibitors. These preliminary data could be used to tailor treatment for RA patients using TNF-α inhibitors.

Pembrolizumab-induced psoriatic arthritis treated with disease-modifying anti-rheumatic drugs in a patient with gastric cancer: A case report.

BACKGROUND: Immune checkpoint inhibitor (ICI)-induced rheumatic immune-related adverse events (irAEs) have been infrequently reported, and the treatment of severe or refractory arthritis as irAEs has not been established yet. CASE SUMMARY: The patient was a 67-year-old man with a history of well-controlled foot psoriasis who presented with polyarthralgia. He had received pembrolizumab for metastatic gastric adenocarcinoma 2 mo previously. Physical examination revealed erythematous swelling in the distal interphalangeal joints, left shoulder, and both knees. He had plaque psoriasis with psoriatic nail dystrophy and dactylitis in the distal joints of the fingers and toes. Inflammatory markers including C-reactive protein and erythrocyte sedimentation rate were elevated but rheumatoid factor and anticyclic citrullinated peptide antibody were negative. The patient was diagnosed with psoriatic arthritis (PsA) and started on methylprednisolone 1 mg/kg/day after pembrolizumab discontinuation. However, despite 1 wk of methylprednisolone treatment, PsA worsened; hence, leflunomide and methotrexate were started. After 4 wk of steroid treatment, PsA worsened and improved repeatedly with steroid tapering. Therefore, the therapy was intensified to include etanercept, a tumor necrosis factor inhibitor, which ultimately resulted in adequate PsA control. CONCLUSION: This is the first report of ICI-induced PsA in a gastric cancer patient. Some rheumatic irAEs with refractory severe arthritis may require disease-modifying anti-rheumatic drugs and long-term management.

Familial risk of seropositive rheumatoid arthritis and interaction with smoking: a population-based cohort study.

OBJECTIVES: We evaluated the familial risk of seropositive rheumatoid arthritis (RA) and examined interactions between family history and smoking. METHODS: Using the National Health Insurance and Health Screening Program databases, which include information on familial relationships and lifestyle factors, we identified 5 524 403 individuals with first-degree relatives (FDRs) from 2002-2018. We calculated familial risk using hazard ratios (HRs) with 95% CIs which compare the risk of individuals with and without affected FDRs. Interactions between smoking and family history were assessed on an additive scale using the relative excess risk due to interaction (RERI). RESULTS: Individuals with affected FDR had 4.52-fold (95% CI 3.98, 5.12) increased risk of disease compared with those with unaffected FDR. Familial risk adjusted for lifestyle factors decreased slightly (HR 4.49), suggesting that a genetic contribution is the predominant driver in the familial aggregation of RA. Smoking was associated with an increased risk of disease that was more pronounced among heavy (HR 1.92 95% CI 1.70, 2.18) compared with moderate (HR 1.15 95% CI 1.04, 1.28) smoking. In the interaction analysis, the risk associated with the combined effect of smoking and family history was higher than the sum of their individual effects, though statistically non-significant (RERI 1.30 95% CI ‒0.92, 3.51). Heavy smokers with a positive family history showed a prominent interaction (RERI 4.13 95% CI ‒0.88, 9.13) which exceeded moderate smokers (RERI 0.61 95% CI ‒1.90, 3.13), suggesting a dose-response interaction pattern. CONCLUSION: Our findings indicate the possibility of an interaction between RA-associated genes and smoking.

Recurrent pulmonary arteriovenous malformation in a patient with Sjögren syndrome: A case report.

RATIONALE: Pulmonary manifestations of Sjögren syndrome (SS) are variable and may involve the airway or lung parenchyma and increase the risk of vascular and malignant disease. However, to date, only one case of pulmonary arteriovenous malformation (AVM) has been reported in a patient with SS. Here, we report a rare case of recurrent pulmonary AVMs with aggravating multiple cysts in a patient with SS during a period of 14 years. PATIENT CONCERNS: A 45-year-old woman was diagnosed with SS and pulmonary AVM in the right lung. Her AVMs were embolized successfully and she was followed up annually for 14 years. Eleven years after the initial treatment, her chest computed tomography showed new pulmonary AVMs in the left lung with aggravating multiple cysts. DIAGNOSIS: We diagnosed her with SS according to the American-European consensus group criteria of 2010. Chest computed tomography and angiographic findings confirmed the recurrence of pulmonary AVMs. INTERVENTIONS: The patient's recurrent pulmonary AVMs were successfully treated by embolization. OUTCOMES: Although her multiple cystic lung lesions had been aggravating during 14 years, she received embolization for the pulmonary AVMs twice and developed no complication related to these procedures. Currently, the patient is 56 years old and still alive with good performance state. LESSONS: To date, only one case of pulmonary AVM has been reported in a patient with SS. The patient died 2.5 years after the diagnosis without recurrence of AVM. Here, we present a rare case of recurrent pulmonary AVMs associated with aggravating multiple cysts in both lungs, which were observed during long-term follow-up, in a patient with SS.

Cardiovascular Risks in Korean Patients with Gout: Analysis Using a National Health Insurance Service Database.

Although several epidemiologic studies have shown the association between gout and cardiovascular outcomes, specific risk factors for developing cardiovascular diseases in Asian patients with gout are undisclosed. Thus, the purpose of this study was to investigate risks of cardiovascular outcomes and its related factors in Korean patients with gout. This retrospective clinical study used sampled cohort data from the National Health Insurance Service in Korea. Patients with gout were defined as subjects enlisted with an ICD-10 code (M10). Control patients were selected by frequency matching for age, sex, and index year. Primary outcomes included ischemic heart disease (IHD), congestive heart failure, cerebrovascular disease (CVD), or transient ischemic attack. We calculated the hazard ratio (HR) using Cox regression, adjusting potential confounders including age, sex, lifestyle habits, laboratory results, and medication. We identified 3306 patients with gout and an equal number of matched controls. Multivariate Cox regression analysis showed that gout patients had increased risks of IHD (HR: 1.860, 95% CI: 1.446-2.392), acute myocardial infarction (HR: 3.246, 95% CI: 1.460-7.217), and CVD (HR: 1.552, 95% CI: 1.177-2.036). Old age, current smoking, frequent alcohol intake, high low-density lipoprotein, and diabetes mellitus increased the risk of cardiovascular outcomes, yet hypouricemic agents decreased the risk of cerebrovascular diseases. Our data corroborate that it is crucial to identify and manage traditional cardiovascular risk factors alongside lowering urate levels in patients with gout.

Association between nuclear factor of activated T cells C2 polymorphisms and treatment response in rheumatoid arthritis patients receiving tumor necrosis factor-alpha inhibitors.

OBJECTIVES: Nuclear factor of activated T cells C2 (NFATC2) is known as a member of the transcription family and enhances tumor necrosis factor-alpha (TNF-α) synthesis in human T cells at the gene transcription level. Although NFATC2 has a potential role in rheumatoid arthritis (RA) progression and treatment, no study has investigated the association between NFATC2 gene polymorphisms and response status in RA patients receiving TNF-α inhibitors. This study aimed to examine the effects of polymorphisms in NFATC2, a TNF-α transcription factor, on response to TNF-α inhibitors. METHODS: This prospective observational study was performed in two centers. Seven single nucleotide polymorphisms (SNPs) were investigated. Good responders were defined as patients with disease activity score (DAS)28 ≤3.2 after 6 months of treatment. Logistic regression analyses were used to investigate the association between genetic polymorphisms and response to the treatment. To test the model's goodness of fit, a Hosmer-Lemeshow test was performed. RESULTS: This study included 98 patients, among whom 46 showed favorable responses to the treatment. Patients with hypertension revealed an approximately three-fold lower response to TNF-α inhibitors compared to those without hypertension (23.5 vs. 76.5%; P = 0.049). After adjusting for covariates, C allele carriers of NFATC2 rs3787186 exhibited approximately three-fold lower rates of treatment response compared to those with TT genotype (P = 0.037). The Hosmer-Lemeshow test showed that the fitness of the multivariable analysis model was satisfactory (χ2 = 9.745; 8 degrees of freedom; P = 0.283). CONCLUSION: This study suggested an association between the C allele of rs3787186 and treatment response in RA patients receiving TNF-α inhibitors.

Clinical Association between Gout and Parkinson's Disease: A Nationwide Population-Based Cohort Study in Korea.

Background and Objectives: This retrospective cohort study aimed to investigate the association between gout and Parkinson's disease (PD) in Korea. Materials and Methods: Overall, 327,160 patients with gout and 327,160 age- and sex-matched controls were selected from the Korean National Health Insurance Service (NHIS) database. PD incidence was evaluated by reviewing NHIS records during the period from 2002 to 2019. Patients with a diagnosis of gout (International Classification of Diseases-10 (ICD-10), M10) who were prescribed medications for gout, including colchicine, allopurinol, febuxostat, and benzbromarone for at least 90 days were selected. Patients with PD who were assigned a diagnosis code (ICD-G20) and were registered in the rare incurable diseases (RID) system were extracted. Results: During follow-up, 912 patients with gout and 929 control participants developed PD. The incidence rate (IR) of overall PD (per 1000 person-years) was not significantly different between both groups (0.35 vs. 0.36 in gout and control groups, respectively). The incidence rate ratio (IRR) was 0.98 (95% CI: 0.89-1.07). The cumulative incidence of PD was not significantly different between the groups. No association between gout and PD was identified in univariate analysis (HR = 1.00, 95% CI: 0.91-1.10, p = 0.935). HR increased significantly with old age (HR = 92.08, 198, and 235.2 for 60-69 years, 70-79 years, and over 80 years, respectively), female sex (HR = 1.21, 95% CI: 1.07-1.37, p = 0.002), stroke (HR = 1.95, 95% CI: 1.76-2.16, p < 0.001), and hypertension (HR = 1.16, 95% CI: 1.01-1.34, p = 0.04). Dyslipidemia exhibited an inverse result for PD (HR = 0.6, 95% CI: 0.52-0.68, p < 0.001). Conclusions: This population-based study did not identify an association between gout and PD. Age, female sex, stroke, and hypertension were identified as independent risk factors for PD, and dyslipidemia demonstrated an inverse result for PD.

Association of TLR 9 gene polymorphisms with remission in patients with rheumatoid arthritis receiving TNF-α inhibitors and development of machine learning models.

Toll-like receptor (TLR)-4 and TLR9 are known to play important roles in the immune system, and several studies have shown their association with the development of rheumatoid arthritis (RA) and regulation of tumor necrosis factor alpha (TNF-α). However, studies that investigate the association between TLR4 or TLR9 gene polymorphisms and remission of the disease in RA patients taking TNF-α inhibitors have yet to be conducted. In this context, this study was designed to investigate the effects of polymorphisms in TLR4 and TLR9 on response to TNF-α inhibitors and to train various models using machine learning approaches to predict remission. A total of six single nucleotide polymorphisms (SNPs) were investigated. Logistic regression analysis was used to investigate the association between genetic polymorphisms and response to treatment. Various machine learning methods were utilized for prediction of remission. After adjusting for covariates, the rate of remission of T-allele carriers of TLR9 rs352139 was about 5 times that of the CC-genotype carriers (95% confidence interval (CI) 1.325-19.231, p = 0.018). Among machine learning algorithms, multivariate logistic regression and elastic net showed the best prediction with the area under the receiver-operating curve (AUROC) value of 0.71 (95% CI 0.597-0.823 for both models). This study showed an association between a TLR9 polymorphism (rs352139) and treatment response in RA patients receiving TNF-α inhibitors. Moreover, this study utilized various machine learning methods for prediction, among which the elastic net provided the best model for remission prediction.

Tocilizumab Increases Body Weight and Serum Adipokine Levels in Patients with Rheumatoid Arthritis Independently of Their Treatment Response: a Retrospective Cohort Study.

BACKGROUND: Causes of weight change after tocilizumab treatment are unclear. We aimed to investigate the effects of tocilizumab treatment on body weight and serum adipokine levels in patients with rheumatoid arthritis (RA). METHODS: In this retrospective cohort study, we evaluated weight changes in patients with RA who received methotrexate (Cohort I) or tocilizumab with methotrexate (Cohorts II and III) for 24 weeks. Adipokine concentrations at baseline and 24 weeks were analyzed in Cohorts I and III. Cohorts I and II received tocilizumab therapy for an additional 48 weeks, during which weight changes were monitored (24-72 weeks). RESULTS: No significant weight change occurred after 24 weeks of methotrexate treatment (mean difference, -0.2 kg; P = 0.630), but was observed after 24 weeks of tocilizumab treatment (mean difference, +0.9 kg; P = 0.010). Weight changed regardless of the treatment response in both treatment groups. The leptin-adiponectin ratio (P = 0.015) and levels of adiponectin (P < 0.001), leptin (P < 0.001), and resistin (P = 0.003) increased significantly after 24 weeks of tocilizumab, but not methotrexate treatment. After 24, 48 and 72 weeks of tocilizumab treatment in Cohort II, mean (95% confidence interval [CI]) weight changes from baseline were +0.7 (0.0-1.4), +1.2 (0.4-2.0) and +1.1 (0.2-2.0) kg, respectively, and mean (95% CI) percent weight changes from baseline were +1.3% (0.1%-2.6%), +2.2% (0.7%-3.6%), and +2.0% (0.4%-3.7%) at 24, 48, and 72 weeks, respectively. CONCLUSION: Weight and the leptin-adiponectin ratio increased after tocilizumab treatment. Given that cardiovascular (CV) risk factors may deteriorate in patients with RA who receive tocilizumab, further studies are required to determine the effects of weight gain on CV outcomes in these patients.

Circulating TNF-like protein 1A (TL1A) is elevated early in rheumatoid arthritis and depends on TNF.

BACKGROUND: The tumor necrosis factor (TNF) superfamily cytokine TNF-like protein 1A (TL1A) and its receptor DR3 are essential for diverse animal models of autoimmune disease and may be pathogenic in rheumatoid arthritis (RA). However, the relationship of TL1A to disease duration, activity, and response to anti-TNF and other therapies in RA is not clear. METHODS: We measured soluble TL1A in synovial fluid (SF), serum, or plasma from RA first-degree relatives (FDRs) and in early RA and established disease. We measured the effects of anti-TNF and methotrexate (MTX) therapy on circulating TL1A from multiple independent RA treatment trials. We also determined the ability of a blocking anti-TL1A antibody to inhibit clinical disease and articular bone destruction in the murine collagen-induced arthritis (CIA) model of human RA. RESULTS: Soluble TL1A was specifically elevated in the blood and SF of patients with RA compared to patients with other diseases and was elevated early in disease and in at-risk anti-cyclic citrullinated peptide (CCP) (+) first-degree relatives (FDRs). Therapeutic TNF inhibition reduced serum TL1A in both responders and non-responders, whereas TL1A declined following MTX treatment only in responders. In murine CIA, TL1A blockade was clinically efficacious and reduced bone erosions. CONCLUSIONS: TL1A is specifically elevated in RA from early in the disease course and in at-risk FDRs. The decline in TL1A after TNF blockade suggests that TL1A levels may be a useful biomarker for TNF activity in RA. These results support the further investigation of the relationship between TL1A and TNF and TL1A blockade as a potential therapeutic strategy in RA.

Long-term efficacy, safety and immunogenicity in patients with rheumatoid arthritis continuing on an etanercept biosimilar (LBEC0101) or switching from reference etanercept to LBEC0101: an open-label extension of a phase III multicentre, randomised, double-blind, parallel-group study.

BACKGROUND: To evaluate the long-term efficacy, safety and immunogenicity of continuing LBEC0101; the etanercept (ETN) biosimilar; or switching from the ETN reference product (RP) to LBEC0101 in patients with rheumatoid arthritis (RA). METHODS: This multicentre, single-arm, open-label extension study enrolled patients who had completed a 52-week randomised, double-blind, parallel phase III trial of LBEC0101 vs ETN-RP. Patients treated with ETN-RP during the randomised controlled trial switched to LBEC0101; those treated with LBEC0101 continued to receive LBEC0101 in this study. LBEC0101 (50 mg) was administered subcutaneously once per week for 48 weeks with a stable dose of methotrexate. Efficacy, safety and immunogenicity of LBEC0101 were assessed up to week 100. RESULTS: A total of 148 patients entered this extension study (70 in the maintenance group and 78 in the switch group). The 28-joint disease activity scores (DAS28)-erythrocyte sedimentation rate (ESR) were maintained in both groups from week 52 to week 100 (from 3.068 to 3.103 in the maintenance group vs. from 3.161 to 3.079 in the switch group). ACR response rates at week 100 for the maintenance vs. switch groups were 79.7% vs. 83.3% for ACR20, 65.2% vs. 66.7% for ACR50 and 44.9% vs. 42.3% for ACR70. The incidence of adverse events and the proportion of patients with newly developed antidrug antibodies were similar in the maintenance and switch groups (70.0% and 70.5%, 1.4% and 1.3%, respectively). CONCLUSIONS: Administration of LBEC0101 showed sustained efficacy and acceptable safety in patients with RA after continued therapy or after switching from ETN-RP to LBEC0101. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02715908 . Registered 22 March 2016.

Clinical and Laboratory Characteristics and Mortality in Korean Patients with Systemic Sclerosis: A Nationwide Multicenter Retrospective Cohort Study.

OBJECTIVE: We aimed to investigate demographic and clinical features and predictors of mortality in Korean patients with systemic sclerosis (SSc). METHODS: We performed a retrospective multicenter medical chart review in Korean patients diagnosed with SSc from 1986 to 2016 at 11 university hospitals representing each geographic area of Korea. SSc patients were defined according to the American College of Rheumatology preliminary classification criteria and subtyped as limited cutaneous (lcSSc) or diffuse cutaneous (dcSSc) SSc. RESULTS: We enrolled 751 patients (female, 86.7%; mean age at diagnosis, 48.9 yrs). The most common organ involvement was interstitial lung disease (52.7%), followed by gastroesophageal reflux disease (32.9%) and pulmonary arterial hypertension (13.6%). Patients with lcSSc were more common than those with dcSSc (64.8 vs 35.2%), whereas anti-Scl-70 and anticentromere antibody positivity were identified in 302 (42.5%) and 175 (25.5%) patients, respectively. In the 46 (6.1%) patients who developed a malignancy, lung cancer (23.9%) was the most common diagnosis, followed by gastric (13%) and breast cancer (13%). During the study period, 57 (7.6%) patients died, and the 5- and 10-year survival rates were 94% and 87%, respectively. Increased age at diagnosis, cardiovascular involvement, and anti-Scl-70 antibody positivity were significant predictors of death. CONCLUSION: Clinical manifestations and survival rates in Korean SSc patients are similar to those of other populations. However, the prevalence of anti-Scl-70 antibody is higher in Korean SSc patients compared with whites, while the prevalence of anticentromere antibody is lower.

Prevalence of co-morbidities and evaluation of their monitoring in Korean patients with rheumatoid arthritis: comparison with the results of an international, cross-sectional study (COMORA).

AIM: We designed this study to evaluate the prevalence of comorbidities, their monitoring states and association with treatment medication in Korean rheumatoid arthritis (RA) patients compared with patients from other countries. METHODS: We analyzed 1050 RA patients from 11 Korean centers and compared them with 3520 patients from 16 other countries using an international, cross-sectional study evaluating comorbidities of RA (COMORA) database. RESULTS: Annual evaluations of cardiovascular (CV) risk were less frequently performed in Korea (P = 0.0011). The prevalence of CV-associated morbidity was similar between Korean and international RA patients, although the proportions of current smokers, patients with a family history of CV disease, patients with hyperlipidemia, and patients with Framingham score > 20% were significantly lower in Korea (P < 0.0001 for all), and the antiplatelet agents were more optimally used in Korea (P = 0.0004). Prostate cancer screening was less frequently performed compared to other countries (P < 0.0001). Less than 10% of Korean RA patients were given influenza and pneumococcal vaccinations according to current recommendations. CONCLUSIONS: There are differences in the prevalence of comorbidities and monitoring states of the risk factors between patients in Korea and in other countries. The prevalence of CV morbidity was similar between the two groups although the prevalence of CV risk factors was significantly low in Korea, suggesting that rheumatologists in Korea need to pay more attention to yearly CV risk monitoring, in addition to the screening of malignancy and vaccination of RA patients against infectious diseases.

GV1001 immunotherapy ameliorates joint inflammation in a murine model of rheumatoid arthritis by modifying collagen-specific T-cell responses and downregulating antigen-presenting cells.

This study investigated whether GV1001 may be useful for treating rheumatoid arthritis (RA). Two collagen-induced arthritis (CIA) experiments showed that therapeutic, but not preventive, GV1001 treatment reduced the severity of joint inflammation in CIA. The third CIA experiment indicated that, compared to vehicle treatment, therapeutic GV1001 treatment was associated with a significantly smaller area under the curve for the overall clinical joint score over the 98day observation period (p<0.05). GV1001 treatment was also associated with lower Day 98 serum IL-6 levels (p<0.01) and histological joint scores (p<0.05). Moreover, splenocytes harvested from the GV1001-treated mice exhibited lower basal and collagen-stimulated production of IFN-γ and IL-6 on Days 49 and 98 than the splenocytes from vehicle-treated mice. The fourth and fifth experiments indicated that earlier treatment resulted in a better response. In addition, human (THP-1) and murine (RAW 264.7) macrophages and fibroblast-like synoviocytes (FLS) from RA patients were used for in vitro analyses. GV1001 treatment of lipopolysaccharide-stimulated macrophages derived from THP-1 and RAW 264.7 monocytes significantly reduced TNF-α and IL-6 secretion (THP-1: all p<0.05; RAW 264.7: all p<0.01). However, GV1001 treatment did not affect IL-6 expression in TNFα-stimulated RA FLS. GV1001 reduced the clinical joint scores, serum IL-6 levels, and histological joint scores of mice with CIA. In addition, GV1001 lowered the collagen-stimulated IFN-γ and IL-6 production of murine T-cells and reduced the TNF-α and IL-6 production of macrophages in vitro. Thus, GV1001 may ameliorate joint inflammation by modifying T-cell reactions to the triggering autoantigen and by reducing macrophage cytokine production.

Association between anti-Porphyromonas gingivalis or anti-α-enolase antibody and severity of periodontitis or rheumatoid arthritis (RA) disease activity in RA.

BACKGROUND: Periodontitis (PD) has been reported to be associated with rheumatoid arthritis (RA). Porphyromonas gingivalis (P. gingivalis) is a gram-negative anaerobic bacterium that is recognized as one of the major pathogenic organisms in PD and is the only bacterium known to express peptidylarginine deiminase (PAD). Antibody against human α-enolase (ENO1) is one of the autoantibodies in RA. ENO1 is a highly conserved protein, and could be a candidate molecule for molecular mimicry between bacterial and human proteins. In the present study, we measured serum antibody against P. gingivalis and human ENO1 in patients with RA and investigated their association with the severity of PD or disease activity of RA. METHODS: Two hundred, forty-eight patients with RA and 85 age- and sex-matched healthy controls were evaluated by rheumatologic and periodontal examinations. The serum levels of anti-P. gingivalis and anti-ENO1 antibodies were measured by an enzyme-linked immunosorbent assay (ELISA). RESULTS: Patients with RA had significantly higher levels of anti-P. gingivalis and anti-ENO1 antibody titers than the controls (p = 0.002 and 0.0001, respectively). Anti-P. gingivalis antibody titers significantly correlated with anti-ENO1 antibody titers in RA patients (r = 0.30, p < 0.0001). There were significant correlations between anti-P. gingivalis antibody titers and the gingival index (GI), probing pocket depth (PPD), bleeding on probing (BOP) and clinical attachment level (CAL) (p = 0.038, 0.004, 0.004 and 0.002, respectively) in RA. Anti-P. gingivalis antibody titers were not correlated with disease activity score 28 (DAS28) or anti-CCP titer. However, anti-ENO1 antibody titers were significantly correlated not only with the periodontal indices, such as PPD, BOP, and CAL (p = 0.013, 0.023 and 0.017, respectively), but also RA clinical characteristics, such as DAS28, anti-CCP titer, and ESR (p = 0.009, 0.015 and 0.001, respectively). CONCLUSION: Anti-P. gingivalis and anti-ENO1 antibody titers were correlated with the severity of PD in RA. Anti-ENO1 antibody titers, but not anti-P. gingivalis antibody titers, were further associated with RA disease activity.

Incidence of malignancy in Takayasu arteritis in Korea.

Cancer is associated with autoimmune diseases. This study aimed to estimate the incidence of cancer in a cohort of patients with Takayasu arteritis (TA) and to compare this incidence with the general population cancer rate in South Korea in a retrospective cohort study. The medical records of TA patients who underwent medical care at our institution between 1979 and 2009 were reviewed. The 2008 National Cancer Registry was used as the reference to calculate the standardized incidence ratio (SIR). The mean age of 180 patients was 48.6 ± 14.3 years, and 87.2 % of the patients were female. During the follow-up of 2,285 person years, 10 females developed cancer. Breast cancer was the most common malignancy with three cases, followed by two endometrial, one gastric, one colon, one pancreatic, one myelodysplastic syndrome (MDS) with refractory anemia with excess blasts, and one multiple myeloma. The SIR of cancer in TA was comparable with that of the general population at 1.3 [95 % confidence interval (CI) 0.6-2.3]; however, the risk of MDS was significantly increased (SIR 51.3; 95 % CI 1.3-285.7). While two patients with hematologic malignancies died, all TA patients with non-hematologic malignancies were still alive during the follow-up period. The overall risk of malignancy is not increased in TA. Further work is needed to determine if TA is associated with an increased risk of certain hematologic malignancies.

Random spot urine protein to creatinine ratio is a reliable measure of proteinuria in lupus nephritis in Koreans.

OBJECTIVES: The accurate assessment of proteinuria is critical for the management of lupus nephritis. Measuring the protein to creatinine (P/C) ratio in random spot urine (RSU) samples has been introduced as an alternative to the 24-hour (24h) urine collection method. However, it remains unclear as to whether the RSU P/C ratio is reliable for assessing lupus nephritis (LN) in routine clinical practice. METHODS: In total, 275 pairs of 24h urine and RSU samples from 102 patients with biopsy-proven LN were analysed. The correlation and concordance between the P/C ratios in the two sample types were assessed by Pearson or Spearman correlation and intra-class correlation coefficient (ICC) using mixed models for repeated measurements, respectively. RESULTS: The mean 24h urine P/C ratio was 3.2 ± 4.9. Overall, RSU P/C ratio correlated strongly with the 24h urine P/C ratio (r=0.944, p<0.001) with an excellent agreement (ICC=0.949, 95% confidence interval [CI]: 0.69-1.00). Subgroup analyses revealed that the correlation remained high in class II, III, IV, and V LN (rho=0.868, p<0.001; rho=0.649, p=0.007; r=0.945, p<0.001; and rho=0.900, p=0.001, respectively). The correlation between the 24h urine and RSU P/C ratio in the range of 0.5 to 3 was good (r=0.720, p<0.001) with ICC of 0.659 (95%CI 0.554-0.812). RSU P/C ratio ≥0.5 could predict 24h PCR ≥0.5 with 91.7% sensitivity and 70.2% specificity, whereas RSU P/C ratio ≥1.0 increased specificity up to 94.7%. CONCLUSIONS: The RSU P/C ratio is an excellent alternative to the 24 hour P/C ratio for assessing the presence of clinically significant proteinuria in LN. RSU P/C ratio >1.0 may prompt directly to a renal biopsy, whereas RSU P/C ratio between 0.5-1.0 should be followed by a confirmatory 24h urine collection.

Hepatitis B virus reactivation in rheumatoid arthritis and ankylosing spondylitis patients treated with anti-TNFα agents: a retrospective analysis of 49 cases.

Clinical guidelines regarding anti-viral prophylaxis for HBV surface antigen (HBsAg) carriers starting anti-TNFα agents are not yet fully established, even in endemic regions of HBV infection. We retrospectively collected the clinical data of 52 HBsAg carriers with rheumatoid arthritis (RA) or ankylosing spondylitis (AS) that had been administered anti-TNFα treatment at seven medical centers in South Korea. Periodic data of liver function tests and serum HBV DNA were both utilized to assess HBV reactivation. The YMDD motif mutation of HBV DNA polymerase was tested in lamivudine-treated patients with elevated HBV DNA. Three of the 52 patients were excluded from the analysis. Of the 49 analyzed patients, 20 patients received anti-viral prophylaxis (15 lamivudine, five entecavir) with anti-TNFα treatment. The remaining 29 patients were treated with anti-viral agents if needed at the discretion of the clinician and did not receive prophylaxis. Of the 29 patients who did not receive primary prophylaxis, two (6.9%) developed viral reactivation within a year of anti-TNFα treatment. In the prophylaxis group, one patient developed viral reactivation at week 64 of anti-TNFα therapy attributed to YMDD mutation caused by lamivudine. Patients with HBV reactivation all responded well to anti-viral therapy. In summary, anti-viral prophylaxis helped preventing HBV reactivation in HBsAg carriers with RA or AS starting anti-TNFα, yet mutation in the YMDD motif of HBV DNA polymerase could be detrimental to some patients under long-term lamivudine prophylaxis.