Circulating cold-inducible RNA-binding protein levels in microscopic polyangiitis and granulomatosis with polyangiitis : Correlation with disease activity.

OBJECTIVE: This study investigated whether circulating cold-inducible RNA-binding protein (CIRP) could be a biomarker to reflect the current activity, function, and damage status in patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). METHODS: This study selected 39 MPA and 26 GPA patients. Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV)-specific indices include the Birmingham Vasculitis Activity Index (BVAS), five-factor score (FFS), the Korean version of the Short-Form 36-Item Health Survey (SF-36) physical component summary (PCS) and mental component summary (MCS), and the vasculitis damage index (VDI). The highest tertile of BVAS was defined as high activity of AAV. RESULTS: The median age of the study subjects was 65.0 years and 53.8% were women. The median BVAS, FFS, SF-36 PCS, MCS, and VDI scores were 12.0, 2.0, 47.5, 50.3, and 3.0, respectively. The median circulating CIRP level was 6.4 ng/mL. Among the four AAV-specific indices, circulating CIRP was significantly correlated with BVAS (r = 0.256). Using the receiver operator characteristic curve, the cut-off of circulating CIRP for high activity of AAV was 6.16 ng/mL. High activity of AAV was identified more frequently in patients with circulating CIRP ≥ 6.16 ng/mL than in those with circulating CIRP < 6.16 ng/mL (48.6% vs. 21.4%). In addition, patients with circulating CIRP ≥ 6.16 ng/mL exhibited a significantly higher risk for high activity of AAV than those with circulating CIRP < 6.16 ng/mL (relative risk 3.474). CONCLUSION: This study suggests the clinical potential of circulating CIRP as a biomarker for reflecting the current BVAS and predicting high activity of AAV in patients with MPA and GPA.

Reclassification of previously diagnosed GPA patients using the 2022 ACR/EULAR classification criteria.

OBJECTIVES: This study applied the 2022 criteria for granulomatosis with polyangiitis (GPA) proposed by the ACR and EULAR (the 2022 ACR/EULAR criteria) to Korean patients with previously diagnosed GPA to investigate the number of patients who could be reclassified as having GPA. METHODS: Sixty-five patients with GPA, who met the 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides and the 2007 European Medicines Agency algorithm for GPA, were included in this study. They were reclassified based on the 2022 ACR/EULAR criteria. RESULTS: Of the 65 patients, 48 patients (73.8%) were reclassified as having GPA. A patient could not be reclassified as having GPA if the patient did not have a total score of 5 despite granulomas on biopsy or clear GPA surrogate markers. Among the 17 patients unclassified as having GPA, 16 patients were reclassified as having MPA and one as having unclassifiable vasculitis, and furthermore, 94.1% of them harboured MPO-ANCA (or perinuclear (P)-ANCA). CONCLUSION: The concordance rate between the 2022 ACR/EULAR criteria for GPA and the previous criteria in patients with previously diagnosed GPA was 73.8%. Although the 2022 ACR/EULAR criteria are the product of the most advanced methodologic process, it should be noted that there were some consequences of distorting the CHCC definition, and further discussion is required, especially with respect to the weightage of the items.

Lung function trajectory of rheumatoid arthritis-associated interstitial lung disease.

OBJECTIVES: To explore the course of lung function and RA disease activity and predictive factors for deteriorating lung function in patients with RA-interstitial lung disease (ILD). METHODS: The Korean Rheumatoid Arthritis-Interstitial Lung Disease cohort is a multicentre, prospective observational cohort. Patients with RA-ILD were enrolled and followed up annually for 3 years for RA disease activity and ILD status assessment. Group-based modelling was used to cluster a similar predicted percentage of forced vital capacity (FVC%) patterns into trajectories. RESULTS: This study included 140 patients who underwent at least two pulmonary function tests. Four distinctive trajectories for predicted FVC% were 'improving' [n = 11 (7.9%)], 'stable' [n = 68 (38.4%)], 'slowly declining' [n = 54 (48.6%)] and 'rapidly declining' [n = 7 (5.0%)]. Most (77.7%) patients maintained or improved to low RA disease activity. The lung function trajectory was not comparable to the RA disease activity trajectory. Age ≥70 years [relative risk (RR) 10.8 (95% CI 1.30, 89.71)] and early RA diagnosed within the preceding 2 years [RR 10.1 (95% CI 1.22, 84.2)] were associated with increased risk for rapidly declining predicted FVC%. The risk for deterioration or mortality increased in patients with a simultaneous diagnosis of RA and ILD within 24 weeks [RR 9.18 (95% CI 2.05, 41.0)] and the extent of lung involvement [RR 3.28 (95% CI 1.12, 9.60)]. CONCLUSION: Most patients with RA-ILD experienced stable or slowly declining lung function. In 5% of patients, predicted FVC% deteriorated rapidly, especially in older adults with early RA. The lung function trajectory was not comparable to the RA disease activity trajectory.

Methotrexate, leflunomide and tacrolimus use and the progression of rheumatoid arthritis-associated interstitial lung disease.

OBJECTIVE: To examine the association between MTX, LEF and tacrolimus use and the progression of RA-associated interstitial lung disease (ILD). METHODS: The Korean RA-ILD cohort prospectively enrolled patients with RA-associated ILD at multiple centres from 2015 to 2018 and followed up with them for 3 years. ILD progression was defined by any of the followings: a decrease of ≥10% in forced vital capacity, a decrease of ≥15% in the diffusing capacity of the lung for carbon monoxide, or death from respiratory failure. RESULTS: Of 143 patients, 64 patients experienced ILD progression during a median follow-up period of 33 months. The use of MTX [adjusted hazard ratio (aHR), 1.06; 95% CI, 0.59, 1.89], LEF (aHR, 1.75; 95% CI, 0.88, 3.46) and tacrolimus (aHR, 0.94; 95% CI, 0.52, 1.72) did not increase the risk of ILD progression. However, the association between LEF use and the risk of ILD progression was significant in subgroups with poor lung function (aHR, 8.42; 95% CI, 2.61, 27.15). Older age, male sex, a shorter RA duration, higher RA disease activity and extensive disease at baseline were independently associated with ILD progression. CONCLUSION: None of the three treatments increased the risk of RA-associated ILD progression, except for LEF, which increased the risk of ILD progression in patients with severe ILD. The appropriate use of conventional synthetic disease-modifying antirheumatic drugs considering RA disease activity and ILD severity would be important for the management of RA-associated ILD.

Serum soluble interleukin-7 receptor alpha levels are negatively correlated with the simultaneous activity of antineutrophil cytoplasmic antibody-associated vasculitis.

OBJECTIVES: This study investigated whether serum soluble interleukin-7 receptor alpha (sIL-7Rα) levels could reflect the simultaneous activity of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: Sixty patients with AAV were included in this study. AAV-related variables and clinical and laboratory data were collected at the two-time points (at early high and late low BVAS) for each patient along with blood sampling. Serum sIL-7Rα levels and the populations of CD3+CD4+ and CD3+CD8+ T cells expressing membranous IL-7Rα (mIL-7Rα) were compared between patients at different time points and between patients and healthy controls. RESULTS: Serum sIL-7Rα levels were significantly lower in AAV patients at early high BVAS than in those at late low BVAS, and the direction of change in serum sIL-7Rα levels increased as BVAS decreased. Serum sIL-7Rα levels were inversely correlated with BVAS, erythrocyte sedimentation rate and C-reactive protein levels. In addition, serum sIL-7Rα levels in AAV patients at early high BVAS exhibited significantly lower levels than those in healthy controls. Particularly, AAV patients at early high BVAS showed significantly increased populations of CD3+ T cells and CD3+CD8+ T cells expressing mIL-7Rα compared to those at late low BVAS. CONCLUSIONS: This study demonstrated that not only serum sIL-7Rα levels but also the populations of CD3+ and CD3+CD8+ T cells expressing m IL-7Rα were negatively correlated with simultaneous BVAS in patients with AAV. Therefore, we suggest that serum sIL-7Rα levels can be an additional and useful biomarker for assessing the simultaneous activity of AAV.

Application of the 2022 ACR/EULAR criteria for microscopic polyangiitis to patients with previously diagnosed microscopic polyangiitis.

OBJECTIVES: This study applied the 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology (the 2022 ACR/EULAR) criteria for microscopic polyangiitis (MPA) to patients with previously diagnosed MPA as per the 2007 European Medicines Agency algorithm (the 2007 EMA algorithm) and the 2012 revised International Chapel Hill Consensus Conference nomenclature of vasculitides (the 2012 CHCC definitions) The concordance rate between the new and old criteria was investigated. METHODS: This study included 117 patients with MPA, and the new criteria were applied to these patients. MPA could be classified when the total score is ≥5. RESULTS: The median age was 64.0 years. The concordance rate between the new and old criteria reached 96.6%. Four patients with previously diagnosed MPA were unclassified. Of these, three patients without myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA) (or perinuclear [P]-ANCA) were not reclassified as having MPA according to the new criteria, despite histopathological findings that were suggestive of MPA based on both the 2007 EMA algorithm and the 2012 CHCC definitions. Conversely, three of four patients with both MPO-ANCA (or P-ANCA) and proteinase 3 (PR3)- ANCA (or cytoplasmic [C]-ANCA) were reclassified as having both MPA and granulomatosis with polyangiitis (GPA) simultaneously according to the 2022 ACR/EULAR criteria for MPA and GPA. CONCLUSIONS: In the new criteria, excessively high score was assigned to MPO-ANCA (or P-ANCA) and MPA-specific histopathological findings were not considered. Hence, the 2007 EMA algorithm and the 2012 CHCC definitions can be applied as additional criteria to complex cases.

Soluble Tyro-3 and Axl may reflect the current activity and renal involvement in patients with microscopic polyangiitis and granulomatosis with polyangiitis.

OBJECTIVES: This study investigated whether soluble Tyro-3 (sTyro-3), sAxl, and sMer could reflect the current activity in patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). METHODS: This study retrospectively reviewed the medical records of 76 patients with MPA and GPA, and measure the serum concentrations of sTyro-3, sAxl, and sMer using the stored serum at AAV diagnosis. Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV)-specific indices included Birmingham vasculitis activity index (BVAS), five-factor score, the short-form 36-item health survey, and vasculitis damage index. High AAV activity was defined as the highest tertile of BVAS. RESULTS: The median age of the 47 MPA and 29 GPA patients was 66.0 years and 43.4% were men. The serum concentrations of sTyro-3 and sAxl were significantly correlated with BVAS and the total score of renal manifestation. The serum concentrations of sTyro-3 and sAxl were independently correlated with BVAS (ß=0.343 and ß=0.310, respectively). In addition, the serum concentrations of sTyro-3 and sAxl were independently associated with the renal involvement of MPA and GPA (OR 1.003 and OR 1.055, respectively). CONCLUSIONS: This study demonstrated the potential of the serum concentrations of sTyro-3 and sAxl to reflect the current activity and renal involvement in patients with MPA and GPA.

Acute Brain Infarction in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Korean Single-Center Study.

OBJECTIVES: This study investigated the clinical and radiological features of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patients with acute brain infarction, using a cohort of Korean patients with AAV. METHODS: This study included 263 patients with AAV. Acute brain infarction was defined as infarction that occurred within 7 days or less. The brain territories affected by acute brain infarction were investigated. Active AAV was arbitrarily defined as the highest tertile of Birmingham Vasculitis Activity Score (BVAS). RESULTS: The median age at diagnosis was 59.0 years, and 35.4% were male. Fourteen cases of acute brain infarction occurred in 12 patients (4.6%), which was calculated as 1332.2 per 100,000 patient-years and 10 times higher than the incidence rate in the Korean general population. Patients with AAV with acute brain infarction exhibited significantly older age, increased BVAS at diagnosis, and a more frequent history of prior brain infarction compared with those without. The brain territories affected in AAV patients were middle cerebral artery (50.0%), multiple territories (35.7%), and posterior cerebral artery (14.3%). Lacunar infarction and microhemorrhage were observed in 42.9% and 71.4% of cases, respectively. Prior brain infarction and BVAS at diagnosis were independently associated with acute brain infarction (hazard ratios, 7.037 and 1.089). Patients with AAV with prior brain infarction or BVAS for active AAV exhibited significantly lower cumulative acute brain infarction-free survival rates than those without. CONCLUSION: Acute brain infarction was observed in 4.6% of AAV patients, and both prior brain infarction and BVAS at diagnosis were independently associated with acute brain infarction.

Application of the 2022 ACR/EULAR criteria for Takayasu arteritis to previously diagnosed patients based on the 1990 ACR criteria.

OBJECTIVES: Recently, a joint group of the American College of Rheumatology (ACR) and the European Alliance of Associations for Rheumatology (EULAR) proposed new criteria for Takayasu arteritis (TAK) (the 2022 ACR/EULAR criteria). This study applied the 2022 ACR/EULAR criteria to patients with previously diagnosed TAK based on the 1990 ACR criteria and investigated the concordance rate between the two criteria according to the four imaging modalities. METHODS: This study reviewed the medical records of 179 patients who met the 1990 ACR criteria for TAK. The imaging modalities included conventional angiography, computed tomography angiography, fluorodeoxyglucose-positron emission tomography, and magnetic resonance angiography. RESULTS: Regardless of the imaging modalities, the concordance rate between the two criteria was 85.5% when including all patients, whereas it increased to 98.1% when only patients aged ≤60 years were included. Among the four imaging modalities, computed tomography angiography exhibited the highest concordance rate between the two criteria (85.6%). The concordance rate among patients aged >60 years was 95.7%. Only one patient aged 50-60 years was reclassified as having both TAK and giant cell arteritis. CONCLUSIONS: The concordance rate was 85.5% regardless of the imaging modalities and increased to 86.9% on simultaneous computed tomography angiography and fluorodeoxyglucose-positron emission tomography imaging.

Serum galectin-9 could be a potential biomarker in assessing the disease activity of antineutrophil cytoplasmic antibody-associated vasculitis.

OBJECTIVES: Serum galectin levels have been reported to be associated with the activity in autoimmune diseases. This study investigated whether serum levels of galectin (Gal)-1, Gal-3, and Gal-9 could be used as biomarkers in assessing the disease activity of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: Eighty AAV patients were selected for inclusion in our AAV cohort. AAV-specific indices and clinical and laboratory data were assessed on the same day when blood samples were obtained from the patient and serum levels of Gal-1, Gal-3, and Gal-9 were measured by ELISA from obtained sera. High disease activity was defined as Birmingham vasculitis activity score (BVAS) ≥ 12. The optimal cut-off value of galectins was extrapolated by receiver operator characteristic analysis and linear and logistic regression analyses were performed to evaluate the association between Gal-3, Gal-9, and BVAS. RESULTS: The median values of BVAS, Gal-1, Gal-3, and Gal-9 were 8.0, 38.1 ng/mL, 12.4 ng/mL, and 1017.7 ng/mL, respectively. Serum Gal-3 and Gal-9 levels were correlated with BVAS (r=0.375 and r=0.462), while only serum Gal-9 levels were independently associated with BVAS (ß=0.250) in linear regression analyses. Serum Gal-9 ≥10.28 ng/mL was also associated with high activity of AAV (odds ratio 5.303) in multivariable logistic regression analysis. In addition, serum Gal-1, Gal-3, and Gal-9 levels were found to differ according to ANCA positivity status and the presence of renal manifestations. CONCLUSIONS: These results suggest the potential possibility of serum Gal-9 levels in assessing AAV disease activity.

Effect of numbers of metabolic syndrome components on mortality in patients with antineutrophil cytoplasmic antibody-associated vasculitis with metabolic syndrome.

OBJECTIVES: This study investigated the effect of the number of metabolic syndrome (MetS) components on all-cause mortality in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) with MetS. METHODS: The medical records of 93 AAV patients with MetS were retrospectively reviewed. MetS was diagnosed when three or more the following MetS components for Asians were met: (i) increased waist circumference; ii) high blood pressure; (iii) hypertriglyceridaemia; (iv) low level of high-density lipoprotein (HDL)-cholesterol; and (v) impaired fasting glucose (IFG) or type 2 diabetes mellitus (T2DM). All-cause mortality was defined as death owing to any aetiology. RESULTS: The median age was 61.4 years and 33 patients were men. Among 93 AAV patients with MetS, as the number of MetS components increased, the cumulative patient survival rate significantly decreased (p = 0.024). Compared to surviving AAV patients with MetS, deceased AAV patients with MetS were older, had higher Birmingham vasculitis activity score (BVAS) and Five-factor score (FFS), a lower frequency of IFG or T2DM, and a higher number of MetS components. In the multivariable Cox analysis, AAV patients with MetS who had all five MetS components were approximately 62 times more susceptible to all-cause mortality than those who had only three components. In terms of IFG or T2DM, patients with only IFG exhibited a significantly lower cumulative patients' survival rate than those without. CONCLUSIONS: The presence of many MetS components at the initial diagnosis of AAV was an independent and significant predictor of all-cause mortality in AAV patients with MetS.

Serum glycated albumin as a predictive biomarker for renal involvement of antineutrophil cytoplasmic antibody-associated vasculitis in non-diabetic patients.

BACKGROUND: Glycated albumin (GA) is known to reflect the current inflammatory burden in non-diabetes mellitus (DM) patients. In this study, we investigated whether GA at diagnosis could reflect the cross-sectional activity and predict poor outcomes during follow-up in non-DM patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: The medical records of 118 immunosuppressive drug-naïve AAV patients were retrospectively reviewed, and 76 patients who had both GA and glycated haemoglobin (HbA1c) results but not DM were included in this study. Demographic, clinical, and laboratory data at diagnosis were assessed. RESULTS: The median age of AAV patients was 61 years, and 31 patients were male. GA was positively correlated with five-factor score (r = 0.282), Birmingham vasculitis activity score (BVAS) assigned to renal manifestation (r = 0.315), and blood urea nitrogen (r = 0.382), whereas negatively correlated with haemoglobin (r = -0.345). AAV patients with end-stage renal disease (ESRD) exhibited significantly higher GA than those without ESRD (15.8% vs. 13.6%). When the cut-off of GA at diagnosis for ESRD was set at GA ≥ 14.25%, AAV patients with GA ≥ 14.25% had a significantly higher risk for ESRD development than those without (relative risk 12.040). In addition, AAV patients with GA ≥ 14.25% exhibited significantly lower cumulative ESRD-free survival rates than those without (P = 0.020). CONCLUSION: In conclusion, GA at diagnosis can reflect the cross-sectional BVAS assigned to renal manifestation of AAV and predict ESRD development during follow-up better than HbA1c or GA/HbA1c in AAV patients.

Predicting the depressive status using empirical dietary inflammatory index in patients with antineutrophil cytoplasmic antibody-associated vasculitis.

BACKGROUND: This study investigated whether the empirical dietary inflammatory index (eDII) score is associated with the inflammatory burden as well as the depressive status in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: Eighty-four patients with AAV participated in this study. Birmingham vasculitis activity score (BVAS) and short-form 36-item Health Survey mental component summary (SF-36 MCS) were considered as indices assessing the inflammatory burden and depressive status, respectively. The eDII includes 16 food components and consists of three groups: -9 to -2, the low eDII group; -1 to +1, the moderate eDII group; and +2 to +10, the high eDII group. Furthermore, the lower eDII group includes both the low and moderate eDII groups. RESULTS: The median age was 64.5 years (36 men). The eDII scores inversely correlated with SF-36 MCS (r = -0.298, p = 0.006) but not with BVAS. SF-36 MCS significantly differ between the lower and higher eDII groups (69.7 vs. 56.7, p = 0.016), but not among the low, moderate and high eDII groups. Additionally, when patients with AAV were divided into two groups according to the upper limit of the lowest tertile of SF-36 MCS of 55.31, patients in the higher eDII group exhibited a significantly higher risk for the lowest tertile of SF-36 MCS than those in the lower eDII group (RR 3.000). CONCLUSION: We demonstrated for the first time that the eDII could predict the depressive status by estimating SF-36 MCS without utilising K-CESD-R ≥ 16 in patients with AAV.

Nutrition Risk Index Score at Diagnosis Can Effectively Predict Poor Prognosis in Patients With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

OBJECTIVES: This study investigated whether the nutritional risk index (NRI) score at diagnosis might be useful for anticipating poor prognosis, in particular, all-cause mortality and end-stage renal disease (ESRD) in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: The medical records of 242 immunosuppressive drug-naïve patients with AAV were retrospectively reviewed. Data at diagnosis and poor prognosis and medications during follow-up were assessed. The NRI score was calculated by 1.519 × serum albumin (g/L) + 41.7 × present (kg)/ideal body weight (kg). RESULTS: The median age at diagnosis of patients with AAV (131 microscopic polyangiitis, 62 granulomatosis with polyangiitis, and 49 eosinophilic granulomatosis with polyangiitis) was 60 years (85 male). During follow-up, twenty-nine patients (12.0%) died after a period of 35.9 months, and 42 patients (17.4%) had ESRD for a period of 30.0 months. Using the receiver operator characteristic curve, the cutoffs of the NRI scores for all-cause mortality and ESRD were calculated as NRI ≤ 101.95 (sensitivity, 46.5%; specificity, 89.7%) and NRI ≤ 99.85 (sensitivity, 57.0%; specificity, 83.3%). In the multivariable Cox hazard model analyses, age (hazard ratio [HR], 1.035), five-factor score (HR, 1.623), and the NRI score ≤ 101.95 (HR, 4.262) were independent predictors of all-cause mortality, whereas, five-factor score (HR, 1.516), hypertension (HR, 1.906), and the NRI score ≤ 99.85 (HR, 3.623) were independent predictors of ESRD occurrence during follow-up in patients with AAV. CONCLUSIONS: The NRI score at diagnosis may be a useful index to anticipate all-cause mortality and ESRD occurrence during follow-up in patients with AAV.

Birmingham vasculitis activity score and the short form 36-item health survey predict current depressive disorders in patients with antineutrophil cytoplasmic antibody-associated vasculitis during the SARS-CoV-2 pandemic.

INTRODUCTION: This study compared the frequency and severity of depressive disorders in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) before and during the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) pandemic using the Korean version of the Center for Epidemiologic Studies Depression Scale-Revised (K-CESD-R) and the Korean version of the Profile of Mood States (K-POMS) depression, and further determined predictors of current depressive disorders in the patients during the pandemic. METHODS: Of the 61 patients with AAV who participated before the pandemic, 8 patients were transferred to other hospitals, 3 patients died, and 2 patients refused to participate in this study. Finally, 48 patients participated in this study. Depression disorders were defined as K­CESD-R ≥ 16. RESULTS: When comparing the patterns of mental health between patients with AAV before and during the pandemic, no change in K­CESD­R or K­POMS subscale scores was observed. Among AAV-related indices, regardless of the pandemic, the short-form 36-item Health Survey (SF-36) mental component score (MCS) and physical component score (PCS) were significantly correlated with K­CESD­R and could predict current depressive disorders. When the cut-off of Birmingham vasculitis activity score (BVAS) for depressive disorders was obtained by the receiver operator characteristic curve, it significantly predicted current depressive disorders in patients with AAV during the pandemic, unlike those before the pandemic. CONCLUSION: We verified that SF-36 MCS and PCS could predict current depressive disorders, regardless of the pandemic, and furthermore, we demonstrated for the first time that BVAS was a predictor of current depressive disorders in patients with AAV during the pandemic unlike those before the pandemic.

Anti-Citrullinated Peptide Antibody Expression and Its Association with Clinical Features and Outcomes in Patients with Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

Background and objectives: Anti-citrullinated peptide antibody (ACPA), a characteristic antibody detected in rheumatoid arthritis, could be linked to antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) via the formation of neutrophil extracellular traps. We investigated the rate of ACPA positivity in patients with AAV and evaluated the association of ACPAs with their clinical features and outcomes. Materials and Methods: A total of 168 AAV patients with both ACPA and ANCA results at diagnosis were identified. Clinical and laboratory variables, including the disease-specific indices of Birmingham Vasculitis Activity Score (BVAS) and Five-Factor Score (FFS), were investigated. All-cause mortality, relapse, and end-stage renal disease, as well as interstitial lung disease (ILD) were evaluated as outcomes of the patients, and the Kaplan-Meier survival analysis was used to compare the event-free survival rates of the groups. Results: Fifteen (8.9%) and 135 (80.4%) patients were positive for ACPA and ANCA, respectively. There were no significant differences in the baseline variables of ACPA-negative and ACPA-positive patients. The absolute titre of ACPAs also did not significantly correlate with BVAS, FFS, erythrocyte sedimentation rate, or C-reactive protein. In addition, there was no difference noted regarding overall, relapse-free, and ESRD-free survival rates between ACPA-negative and ACPA-positive AAV patients. However, when the patients were divided into four groups according to ACPA and ANCA status, differences were present in the outcomes, and the ACPA-positive ANCA-positive group exhibited the lowest cumulative relapse-free survival rate, while no significant difference was present in the relapse between the ANCA-positive ANCA-positive, ACPA-positive ANCA-negative, and ACPA-negative ANCA-positive groups. Finally, the cumulative ILD-free survival rates were comparable between ACPA-positive and ACPA-negative AAV patients. Conclusions: The detection of ACPA expression is not uncommon in AAV. However, the presence of ACPA did not influence patients' basal characteristics and outcomes, suggesting that further exploration of the role of this antibody is needed in patients with AAV.

Significance of antineutrophil cytoplasmic antibody positivity in patients with systemic sclerosis: a single-centre pilot study in Korea.

OBJECTIVES: We investigated whether antineutrophil cytoplasmic antibody (ANCA) positivity at diagnosis may be associated with the cross-sectional clinical features at diagnosis and predicting all-cause mortality during follow-up in Korean patients with systemic sclerosis (SSc). In addition, we assessed the incidence of SSc and ANCA-associated vasculitis (AAV) overlap syndrome in patients with ANCA positivity. METHODS: We retrospectively reviewed the clinical and laboratory features through the medical records of 177 SSc patients who fulfilled the inclusion and exclusion criteria. SSc was classified by the 2013 American College of Rheumatology/European League Against Rheumatism classification criteria. AAV was classified by the 2007 European Medicine Agency algorithms and the 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. RESULTS: The median age was 52 years, and 23 patients were males. The detection rate of ANCA in Korean patients with SSc was 20.3%. Unlike a previous study, ANCA positivity at diagnosis was significantly associated with neither the cross-sectional clinical and laboratory variables at diagnosis nor the rate of all-cause mortality during follow-up in Korean patients with SSc. However, three female patients (8.3%) with ANCA could be classified as having microscopic polyangiitis (MPA) during follow-up. CONCLUSIONS: No significant associations of ANCA positivity with the cross-section clinical features or all-cause mortality during follow-up were observed in this study. But, given that 3 of 36 SSc patients with ANCA were classified as having AAV based on the histological confirmation, we suggest that physicians should consider recommending a biopsy when AAV is strongly suspected in SSc patients with ANCA.

D-dimer predicts poor hospitalisation outcomes in patients with antineutrophil cytoplasmic autoantibody-associated vasculitis.

OBJECTIVES: The in-hospital mortality rate among patients with antineutrophil cytoplasmic autoantibody-associated vasculitis (AAV) is high. Unfortunately, there is no reliable prognostic biomarker. This study aimed to investigate whether elevated D-dimer levels can predict hospitalisation outcomes among patients with AAV. METHODS: We performed a retrospective analysis at a tertiary medical centre in Seoul, South Korea, between 2005 and 2019. Patients with AAV requiring hospitalisation, whose D-dimer levels were available within one week of hospitalisation, were included; patients with known alternative reasons for elevated D-dimer were excluded. Death and intensive care unit requirements were defined as adverse outcomes. RESULTS: In total, 61 AAV patients with a total of 100 episodes of hospitalisation were included. Median D-dimer levels were significantly higher in patients with adverse outcomes than in those without adverse outcomes (1.84 vs. 0.42 mg/dL; p=0.006). Consistently, the incidence of the adverse outcomes was significantly higher in the high D-dimer group (≥0.699 mg/dL; n = 40) than in the low D-dimer group (<0.699 mg/dL; n = 60) (35% vs. 10%; p=0.002). Multivariate logistic regression analysis revealed that a high D-dimer level was a significant risk factor for adverse outcomes (hazard ratio, 4.852; 95% confidence interval, 1.320-17.833; p=0.017). Kaplan-Meier survival analysis revealed that the high D-dimer group was associated with more 30-day in-hospital adverse outcomes than the low D-dimer group (p=0.008). CONCLUSIONS: High D-dimer levels on admission are significantly associated with adverse outcomes among patients with AAV.

Pan-immune-inflammation value at diagnosis independently predicts all-cause mortality in patients with antineutrophil cytoplasmic antibody-associated vasculitis.

OBJECTIVES: The pan-immune-inflammation value (PIIV), a novel, validated predictor of the prognosis of several diseases, has been recently introduced. We investigated whether PIIV at diagnosis could predict all-cause mortality during follow-up in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: Medical records of 219 immunosuppressive drug-naïve patients with AAV were reviewed. PIIV was calculated as follows: neutrophil count (x 1000/m3) x monocyte count (x 1000/m3) x platelet count (x 1000/mm3) / lymphocyte count (x 1000/m3). Additionally, conventional risk factors of mortality, AAV-specific indices, and acute-phase reactants at diagnosis were evaluated. RESULTS: The median age at diagnosis was 59.0 years and 32.9% of the patients were male. During follow-up, 24 patients (11.0%) died due to all causes. When the cut-off of PIIV at diagnosis for all-cause mortality was set at 1011.3, sensitivity and specificity of 52.0% and 71.2%, were attained (p=0.041). When AAV patients were divided into two groups according to the calculated cut-off, those with PIIV ≥1011.3 at diagnosis had a significantly lower cumulative survival rate than those without (p=0.009). In the multivariable Cox hazards model analysis, male gender (HR 2.307), FFS (HR 1.728) and PIIV ≥1011.3 (HR 2.689) were identified as significant and independent risk factors of all-cause mortality. CONCLUSIONS: PIIV at diagnosis exceeding the optimal cut-off for death could predict all-cause mortality during follow-up in AAV patients comparable to male gender and FFS at diagnosis.

Clinical significance of large unstained cell count in estimating the current activity of antineutrophil cytoplasmic antibody-associated vasculitis.

BACKGROUND: We investigated whether large unstained cell (LUC) count could estimate the current high activity according to Birmingham vasculitis activity score (BVAS) in patients with antineutrophil cytoplasmic antibody (ANCA) positive ANCA-associated vasculitis (AAV). METHODS: We retrospectively reviewed the medical records of 176 immunosuppressive drug-naïve patients with ANCA positive AAV. Clinical and laboratory data at diagnosis, including LUC count, were collected. High BVAS was defined as the highest tertile of BVAS (BVAS ≥ 15) in this study. RESULTS: The median age was 61.0 years, and 64.8% were female. The median LUC count was 60.0 mm3 , and LUC was detected in 106 patients. LUC count was significantly correlated with BVAS, age, white blood cell count, haemoglobin, platelet count, serum albumin, erythrocyte sedimentation rate and C-reactive protein. Overall, the median BVAS in AAV patients with LUC positivity was significantly higher than that in those without (14.0 vs 10.0). When the cut-off of LUC count for the current high BVAS was set as BVAS ≥ 15 mm3 , AAV patients with LUC count ≥ 15 mm3 had a significantly higher risk for the current high BVAS than those with LUC count < 15 mm3 (relative risk 2.596). However, in the multivariable linear and logistic regression analyses, LUC did not seem to estimate the current BVAS independently among clinical and laboratory variables. CONCLUSION: LUC count was significantly correlated with the current BVAS and LUC count ≥ 15 mm3 could estimate the current high BVAS in patients with ANCA positive AAV.