Clinical impact of proteinase 3-antineutrophil cytoplasmic antibody positivity in eosinophilic granulomatosis with polyangiitis

Sung Soo Ahn,Jason Jungsik Song,Yong-Beom Park,Sang-Won Lee 대한내과학회 2022 The Korean Journal of Internal Medicine Vol.37 No.6

Background/Aims: This study investigated the clinical implication of proteinase 3 (PR3)-antineutrophil cytoplasmic antibody (ANCA) in Korean patients with eosinophilic granulomatosis with polyangiitis (EGPA). Methods: Among the 242 patients with ANCA-associated vasculitis identified from the hospital database, 49 patients with EGPA were selected and analysed in this study. Demographic, clinical, and laboratory data at diagnosis were reviewed to compare the features of patients with PR3-ANCA and without, as well as the clinical outcomes of relapse and end-stage renal disease (ESRD) during the follow-up period. The outcomes of patients with PR3-ANCA and without were compared by using the Kaplan-Meier survival analysis. Results: The median age of the patients was 54 years, 17 (34.7%) were male, and six (12.2%) patients had PR3-ANCA at baseline. The most common items of the 1990 American College of Rheumatology criteria for EGPA were sinusitis (95.9%) and asthma (or asthmatic history) (93.9%). During the follow-up, none died, eight experienced relapse and two progressed to ESRD. EGPA patients with PR3-ANCA exhibited peripheral eosinophilia less frequently than those without (50.0% vs. 88.4%, p = 0.047). On the other hand, EGPA patients with PR3-ANCA experienced relapse more often compared to those without (50.0% vs. 11.6%, p = 0.047), and the cumulative relapse-free survival rate was lower compared to those without PR3-ANCA (p = 0.012). Conclusions: EGPA patients possessing PR3-ANCA at disease diagnosis had distinct clinical feature and outcome compared to those without PR3-ANCA. These results should be taken into account in the management of patients with EGPA.

Clinical features of Korean elderly patients with antineutrophil cytoplasmic antibody-associated vasculitis

( Byung-woo Yoo ),( Jason Jungsik Song ),( Yong-beom Park ),( Sang-won Lee ) 대한내과학회 2021 The Korean Journal of Internal Medicine Vol.36 No.3

Background/Aims: We compared the clinical and laboratory data between elderly and non-elderly patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) at diagnosis; further, we investigated the predictors at diagnosis for all-cause mortality and end-stage renal disease (ESRD) occurrence during follow-up in Korean elderly patients with AAV. Methods: We reviewed the medical records of 191 AAV patients regarding clinical manifestations and laboratory results at diagnosis and during follow-up. The follow-up duration was defined as the period from diagnosis to death for deceased patients or to the time of dialysis for ESRD patients, or to the last visit. Elderly (n = 67) and non-elderly (n = 124) patients were grouped based on an age threshold of 65 years. Results: At diagnosis, elderly patients exhibited higher median Birmingham Vasculitis Activity Score (BVAS) and higher frequencies of ANCA positivity and pulmonary manifestations than non-elderly patients. Furthermore, elderly patients exhibited increased median white blood cell count, blood urea nitrogen (BUN), alkaline phosphatase, erythrocyte sedimentation rate, and C-reactive protein and decreased median hemoglobin. However, there were no significant differences in all-cause mortality and ESRD occurrence between elderly and non-elderly patients. Meanwhile, elderly patients exhibited lower cumulative patients’ and ESRD-free survival rates than non-elderly patients. In the multivariable Cox hazards model, BUN, creatinine and serum albumin at diagnosis were independent predictors for ESRD occurrence, whereas there were no independent predictors at diagnosis for all-cause mortality. Conclusions: Elderly AAV patients exhibited substantially higher rates of all-cause mortality and ESRD occurrence during follow-up compared than non-elderly AAV patients.

Platelet to lymphocyte ratio is associated with the current activity of ANCA-associated vasculitis at diagnosis: a retrospective monocentric study

Park, Hee Jin,Jung, Seung Min,Song, Jason Jungsik,Park, Yong-Beom,Lee, Sang-Won Springer-Verlag 2018 Rheumatology international Vol.38 No.10

Hemoglobin A1c, Not Glycated Albumin, Can Independently Reflect the Ankylosing Spondylitis Disease Activity Score

( Sejin Byun ),( Seung Min Jung ),( Jason Jungsik Song ),( Yong-beom Park ),( Sang-won Lee ) 대한류마티스학회 2018 대한류마티스학회지 Vol.25 No.2

Objective. This study examined whether glycated hemoglobin (HbA1c) and glycated albumin (GA) are well correlated with the Ankylosing Spondylitis Disease Activity Score (ASDAS)-erythrocyte sedimentation rate (ESR), and ASDAS-C-reactive protein (CRP) in AS patients without medical conditions affecting the glycated protein levels. Methods: The data of 76 patients with AS were analyzed. Univariate and multivariate analyses of the variables associated with ASDAS-ESR and ASDAS-CRP were performed using a linear regression test. The patients were divided into active and inactive AS groups based on an ASDAS-CRP of 2.1, and the variables between the two groups were compared. Results. ASDAS-ESR did not correlated with either HbA1c or GA. ASDAS-CRP was positively correlated with HbA1c (r=0.315, p=0.006) and the white blood cell (r=0.288, p=0.012), and inversely correlated with hemoglobin (r=-0.241, p=0.036) and serum albumin (r=-0.262, p=0.022), but not GA. Multivariate analysis revealed HbA1c and white blood cell to be significantly correlated with ASDAS-CRP (β=0.234, p=0.033 and β=0.265, p=0.017). The mean HbA1c, not GA, of the active group was significantly higher than that of the inactive group (p=0.020). In addition, the optimal cut-off value of HbA1c was set to 5.6, and the patients with HbA1c ≥5.6 were found to have a 3.3 times higher risk of active AS than those without. Conclusion. HbA1c was significantly correlated with ASDAS-CRP, and could be a useful marker to reflect ASDAS-CRP in AS patients without medical conditions affecting the glycated protein levels. (J Rheum Dis 2018;25:131-139)

Platelet Distribution Width and Mean Platelet Volume Are Not Correlated with the Disease Activity Indices of Ankylosing Spondylitis

( Sejin Byun ),( Seung Min Jung ),( Jason Jungsik Song ),( Yong-beom Park ),( Sang-won Lee ) 대한류마티스학회 2017 대한류마티스학회지 Vol.24 No.3

Objective. We investigated the association of platelet distribution width (PDW) and mean platelet volume (MPV) with disease activity indices of ankylosing spondylitis (AS) in patients whose laboratory results or medical conditions would not affect PDW and MPV levels. Methods. We analysed demographic and laboratory data of 88 patients with AS. On the same day as the laboratory tests were done, we assessed AS disease activity using the Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Patients Global Score and Ankylosing Spondylitis Disease Activity Score (ASDAS), including erythrocyte sedimentation rate (ESR) (ASDAS-ESR) and C-reactive protein (CRP) (ASDAS-CRP). The association was analyzed by linear regression. Results. The median age of 88 patients was 38.0 years and the median length of observation was 5.5 years. The median platelet count was 266,500.0/μL, the median PDW was 10.7 fL and the median MPV 9.6 fL. The median ESR was 19.0 mm/hr and CRP was 2.5 mg/L. Among acute reactants, only CRP was negatively correlated with MPV, but not PDW (r=-0.218, p<0.041). However, both PDW and MPV were not significantly correlated with any disease activity index of AS. On multivariate linear regression analysis, only the length of observation was significantly correlated with MPV (β=0.224, p<0.044). Conclusion. PDW and MPV were not potent surrogate markers to reflect AS activity, with potential confounding strictly controlled, to affect MPV and PDW levels. (J Rheum Dis 2017;24:143-148)

Modified Body Mass Index at Diagnosis is a Useful Predictor of Mortality in Patients With Antineutrophil Cytoplasmic Antibody-associated Vasculitis

( Jung Yoon Pyo ),( Sung Soo Ahn ),( Jason Jungsik Song ),( Yong-beom Park ),( Sang-won Lee ) 대한류마티스학회 2022 대한류마티스학회지 Vol.29 No.3

Objective: We investigated whether modified body mass index (mBMI) at diagnosis could predict all-cause mortality during follow-up in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Methods: The medical records of 203 AAV patients with BMI ≥18.5 kg/m² were reviewed. mBMI was calculated using an equation: mBMI=BMI (kg/m²)×serum albumin (g/L). All-cause mortality was considered as a poor outcome, and the follow-up duration based on all-cause mortality was defined as the period from AAV diagnosis to death for deceased patients, and the period from AAV diagnosis to the last visit for surviving patients. Results: The median age was 59.0 years (35.5% were male). The median BMI and mBMI were 22.8 kg/m² and 813.2 kg · g/m² · L. Twenty-five patients (12.3%) died. mBMI was well correlated with age, BVAS, FFS, erythrocyte sedimentation rate and C-reactive protein at diagnosis. Deceased patients exhibited significantly lower mBMI at diagnosis compared to surviving patients. AAV patients mBMI ≤570.1 kg · g/m² · L showed a significantly higher frequency of all-cause mortality (38.5% vs. 8.5%), and furthermore, exhibited a significantly higher risk for all-cause mortality than those with mBMI >570.1 kg · g/m² · L (RR 6.750). mBMI ≤570.1 kg · g/m² · L showed a significantly lower cumulative patients’ survival rate than those with mBMI >570.1 kg · g/m² · L. In the multivariable Cox hazards model analysis, either serum albumin or mBMI was significantly associated with all-cause mortality in AAV patients. Conclusion: In conclusion, mBMI ≤570.1 kg · g/m² · L at diagnosis may be a useful predictor of all-cause mortality during followup additionally to serum albumin in AAV patients.

Lipid Profiles in Anti-neutrophil Cytoplasmic Antibody-associated Vasculitis: A Cross-sectional Analysis

( Sung Soo Ahn ),( Taejun Yoon ),( Jason Jungsik Song ),( Yong-beom Park ),( Sang-won Lee ) 대한류마티스학회 2020 대한류마티스학회지 Vol.27 No.4

Objective. Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an autoimmune disease (AID) characterised by necrotising intravascular inflammation. Growing evidence suggests that immune system triggers altered lipid metabolism in AIDs. We investigated whether changes in lipid profile correlate with severity of disease in AAV. Methods. Seven lipid profiles were evaluated utilizing frozen serum samples from 67 patients registered in the Severance Hospital ANCA-associated VasculitidEs cohort by a chemistry autoanalyzer. The Birmingham Vasculitis Activity Score (BVAS) version 3 was used to measure patient’s assessment of global disease activity. The relationship between the BVAS with continuous variables was calculated by Pearson’s correlation analysis. Results. Thirty-five (52.2%), 19 (28.4%), and 13 (19.4%) patients were diagnosed with microscopic polyangiitis, granulomatosis with polyangiitis, and eosinophilic granulomatosis with polyangiitis, respectively. Patients’ mean age was 60.0 years, and 22 (32.8%) were male. Among the lipid profiles investigated, total cholesterol, high-density lipoprotein, and low-density lipoprotein, and apolipoprotein A1 and B were significantly associated with BVAS; apolipoprotein A1 showed the highest correlation with BVAS (r=-0.521, p<0.001), remaining consistent even in patients with new-onset disease (r=-0.430, p=0.012). Apolipoprotein A1 had the highest association with the renal manifestation score among the clinical scores comprising BVAS (r=-0.457, p<0.001). Conclusion. Decreased lipid levels, especially apolipoprotein A1, are relevant to increased AAV disease activity, and differ according to organ involvement. Measuring lipid profiles could have clinical implications regarding the assessment of global disease activity and organ involvement patterns. (J Rheum Dis 2020;27:261 -269)

Safety of Tocilizumab in Rheumatoid Arthritis Patients with Resolved Hepatitis B Virus Infection: Data from Real-World Experience

Ahn, Sung Soo,Jung, Seung Min,Song, Jason Jungsik,Park, Yong-Beom,Park, Jun Yong,Lee, Sang-Won Yonsei University, College of Medicine 2018 Yonsei medical journal Vol.59 No.3

<P>To investigate whether the use of IL-6 receptor antagonist (tocilizumab) might be associated with hepatitis B virus (HBV) reactivation in rheumatoid arthritis (RA) patients, particularly in those with resolved HBV infection [HBV surface antigen (HBsAg) negative and antibody to HBV core antigen (anti-HBc) positive, serologically]. HBsAg, anti-HBc, antibody to HBsAg (anti-HBs), and HBV DNA titers were measured in RA patients who had continuously received tocilizumab for more than 3 months. Patients were divided into two groups according to the presence of anti-HBc. Clinical and laboratory data, in addition to medications administered along with tocilizumab during the treatment duration with tocilizumab, were compared between the two groups. HBV reactivation was defined as the presence of HBV DNA in sera, and alterations in HBsAg, anti-HBc, and anti-HBs titers according to the use of tocilizumab were also evaluated. Fifteen of 39 patients (38.5%) had anti-HBc positivity, while 24 patients (61.5%) did not. There were no differences in demographic data, serologic classification, and variables related to tocilizumab between the anti-HBc-positive and -negative groups. Comparison of the medications administered along with tocilizumab treatment revealed no meaningful differences. None of the patients experienced reactivation of HBV. In addition, in 15 patients with resolved HBV infection, no alterations in HBsAg, anti-HBc, and anti-HBs titers were observed with the use of tocilizumab. Tocilizumab may be applied to RA patients safely with few concerns for HBV reactivation, particularly in those with resolved HBV infection.</P>

Serum anti-lysozyme is associated with disease activity of Behiet’s disease

( Jin-su Park ),( Mi-il Kang ),( Jason Jungsik Song ),( Yong-beom Park ),( Soo-kon Lee ),( Chan Hee Lee ),( Sang-won Lee ) 대한내과학회 2015 대한내과학회 추계학술대회 Vol.2015 No.1

Objectives: We investigated the association between autoantibodies against non- myeloperoxidase (MPO) neutrophil granule antigens and activity of Behiet’s disease (BD). Methods: We consecutively enrolled 51 BD patients. We assessed clinical data and BD activity using patients index score of Behiet’s Disease Current Activity Form. And we performed tests for antibodies against proteinase 3 (PR3), MPO, bactericidal permeability increasing protein (BPI), cathepsin G, elastase, lactoferrin and lysozyme. Results: The median patient index score was 2.0, and 56.9% of patients had active BD. In multivariate analysis of variables with significant correlations, only anti-lysozyme showed a significant correlation with BD activity (p=0.002). In multivariate logistic regression analyses of variables, when patients were classified into groups according to the optimal cutoff levels of ESR, CRP and anti-lysozyme (ESR>42.5 mm/hr, CRP>1.35 mg/L and anti-lysozyme>2.95 IU/mL), the variable with independent predictive value was anti-lysozyme (OR 8.384, p=0.015) Conclusions: Anti-lysozyme was significantly correlated with disease activity score and it was only independent value to predict active disease in patients with BD. Furthermore, patients having anti-lysozyme level ≥ 2.95 IU/mL had a significantly higher risk of having active BD than those not.

Low serum complement 3 level is associated with severe ANCA-associated vasculitis at diagnosis

Choi, Hyeok,Kim, Youhyun,Jung, Seung Min,Song, Jason Jungsik,Park, Yong-Beom,Lee, Sang-Won Tokyo; OCC Japan 2019 CLINICAL AND EXPERIMENTAL NEPHROLOGY Vol.23 No.2