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.

Increased Circulating PD-1 hi CXCR5 - Peripheral T Helper Cells are Associated with Disease Activity of ANCA-Associated Vasculitis.

Newly identified PD-1 hiCXCR5 -CD4 + T cells, termed as peripheral helper T cells (Tph), have been found elevated and playing pathogenic role in some autoimmune diseases like systemic lupus erythematosus (SLE) and rheumatic arthritis (RA). However, the potential role of Tph cells in Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) remains unclear. Here, we explored the potential clinical significance of circulating Tph cells in the pathogenesis of AAV. Comparing 32 active AAV patients and 18 age- and sex-matched healthy controls (HCs), we found that the frequency of circulating Tph cells was significantly expanded in active AAV patients. Besides, programmed death 1 (PD-1) expression on the surface of Tph cells was significantly up-regulated in active AAV patients. Importantly, the frequency of circulating Tph cells was greatly decreased in AAV patients after receiving treatment. Tph cells frequency was positively correlated with the Birmingham Vasculitis Activity Score (BVAS), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), neutrophil lymphocyte ratio (NLR) and cellular crescent in active AAV patients, but negatively correlated with fibrosus crescent. Tph cells frequency was also positively correlated with naïve B cells, serum concentration of MPO-ANCAs, serum tumor necrosis factor-α (TNF-α), IL-4, IL-21 and IL-12. However, serum IL-10 exhibited negative correlation with circulating Tph cells in active AAV patients. These results demonstrated that circulating Tph cells are greatly expanded in active AAV patients and are positively associated with serum MPO-ANCAs and disease activity, thus contributing to the pathogenesis of AAV.

ANCA-Associated Vasculitis Clinical Presentation and Clinical Predictors of Relapse in Saudi Arabia.

BACKGROUND: Anti-neutrophil cytoplasm antibodies-associated vasculitis (AAV) is a rare autoimmune condition with high-relapsing rate and incidence of complications, resulting in increased morbidity and mortality. Characters of patients with anti-neutrophil cytoplasm antibodies-associated vasculitis in Saudi Arabia require further exploration. OBJECTIVE: To evaluate the clinical profile, relapse rate and disease-related complications among patients with AAV at a tertiary hospital in Saudi Arabia. To estimate the role of BVAS score at the time of presentation in predicting relapse during the disease course. DESIGN AND SETTING: This retrospective cohort study was performed through data collection from patients' records who had AAV, who visited the rheumatology clinic. The collected data involved the demographics of patients and their investigations, medications, and outcomes of treatment. Statistical analysis was executed through SPSS version 26. RESULTS: Fifty-two patients were eligible for inclusion, while 48 patients were analyzed because of missing data. Females represented 60.4%. Half of the patients were more than 50 years old, and 68.8% had comorbidities. As for diagnosis, 62.5% had granulomatosis with polyangiitis, 25% had eosinophilic granulomatosis with polyangiitis, and 12.5% had microscopic polyangiitis. The rate of relapse was 31.3%, while the remission rate was 68.8%. Additionally, 66.7% had lower respiratory involvement, and 43.8% had renal involvement. More than half of the patients had BVAS score below 14.5 points. The study did not explore a positive correlation between the disease relapse and high BVAS at the first presentation. CONCLUSION: Early prediction of relapse and such intervention is of paramount importance in order to avoid accrual of organ damage with treatments that prevent further relapses. BVAS score was not found to be a potential predictor in our study. Future studies are highly endorsed, with prospective design and large sample size to achieve statistical significance for the incidence of relapses and complications.

Comparison of Granulomatosis with Polyangiitis Clinical Features in Patients Depending on Involvement or Absence of Kidney Involvement.

BACKGROUND: GPA is necrotizing inflammation of the small vessels with granulomas. Kidney involvement deteriorated its prognosis. OBJECTIVE: Comparison of GPA patients with Kidney (KI) and without Kidney Involvement (nKI). MATERIALS AND METHODS: We conducted a cross-sectional study of 50 consecutive adult GPA patients, 25 KI from Nephrology and 25 nKI from the Rheumatology Department of Central Clinical Hospital Ministry of Interior in Warsaw. We analyzed clinical features, organ involvement, laboratory, serological, imaging, histopathological data, BVAS and treatment. RESULTS: The mean age of KI patients was statistically older than nKI (67.3±9.5 vs. 55.1±15.9, p=0.002). Generalized, severe, disease resistance was observed respectively in 92% vs. 44%, p<0.001. The number of red blood cells (3.47 vs. 4.41T/l, p<0.001), hemoglobin (10.0 vs. 12.9 g/dl, p<0.001) was lower in KI, higher mean serum creatinine (3.95 vs. 0.89 mg/dl, p<0.001), lower GFR (20.1 vs. 79.3, p<0.001), higher CRP (median: 43.4 vs. 2.0 mg/l, p<0.001), BVAS (16.6±4.4 vs. 10.1±6.2, p<0.001), c-ANCA (median: 119.0 vs. 15.2CU, p=0.017). Nodules in 28% KI, in 4% nKI (p=0.048) in chest X-ray, infiltration in 43.5% KI, in 15% nKI (p=0.042) in HRCT were observed. Skin granulomas were found in 61.5% nKI vs. 18.2% KI, (p=0.047). Renal biopsy revealed in KI patients focal segmental glomerulonephritis in 11.8%, crescentic glomerulonephritis in 17.6%, and pauci-immune crescentic glomerulonephritis in 70.6%. CONCLUSION: In patients with KI we found generalized, severe, resistant GPA, higher BVAS more frequently than inpatients without KI. The results of laboratory parameters were worse in patients with KI. Aggressive immunosuppressive treatment is often used in the KI group.

Clinical characteristics and long-term outcome of Takayasu arteritis in Iran: a multicentre study

Background/aim: This study aimed to evaluate the demographic, clinical, angiographic and prognostic characteristics of Takayasu arteritis (TA) in Iran. Materials and methods: A total of 75 patients with TA based on the American College of Rheumatology 1990 criteria for TA classification referred to the Rheumatology Centres, were followed-up from 1989 to 2019. Demographic, clinical, angiographic and prognostic characteristics were collected at baseline and last visit. Results: The mean age was 31.9 ± 9.8 years at the disease onset. Female to male ratio was 14. The median latency in diagnosis was 24 months. Pulse discrepancy in the arms, blood pressure discrepancy in the arms, limb claudication, hypertension and constitutional symptoms were the most common clinical features. The most common angiographic type at the time of diagnosis was Type I (42.7%). The most frequent arterial lesion was stenosis (89.4%). Subclavian, carotid and aortic arteries were the most commonly involved arteries. New lesions developed in 28.6% of patients during the 5.25-year follow-up. Vasculitis-induced chronic damage was observed in all patients. Disease activity decreased and vascular damage remained stable throughout the follow-up period. Conclusions: The clinical features and angiographic type of TA in Iran are different from most Asian countries. Differences in angiographic and clinical features may lead to delayed diagnosis. The issue of delay in diagnosis should create awareness among health care providers that TA is not a very rare disease in Iranians and failure to pay attention to warning symptoms may delay the diagnosis.

Measuring Vasculitis with Numbers: Outcome Scores.

Primary Systemic Vasculitides (PSV) are a heterogeneous group of diseases. Outcome scores are important to evaluate vasculitis patients in a more structured and standard way and these help physicians to predict patients with poor prognosis or high risk of relapse. Furthermore, we need reliable outcome measures for clinical trials. There are a number of vasculitis outcome scores available in the clinical practice with different strengths and limitations. These are mainly measures of disease activity, disease damage, response to treatment and quality of life. Birmingham Vasculitis Activity Score (BVAS) and its pediatric version aim to evaluate a wide scope of PSV. On the other hand, some outcome studies have focused on a single vasculitis type since the whole group includes different diseases with heterogeneous clinical features. The aim of this review is to provide an overview on outcome measures currently being used in the evaluation of patients with PSV. We mainly focus on immunoglobulin A vasculitis/Henochschönlein purpura, Kawasaki disease, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, polyarteritis nodosa, Takayasu arteritis and Behçet's disease.

Cytokine profiling in anti neutrophil cytoplasmic antibody-associated vasculitis: a cross-sectional cohort study.

ANCA-associated vasculitides (AAV) are severe diseases, potentially affecting lungs, kidney, and other organs. Nevertheless, risk profiling remains difficult. Aim of the current study was to analyze serological characteristics in AAV. The principal goal was to identify diagnostic markers that potentially allow a more sophisticated risk profiling in AAV. AAV subjects were recruited and evaluated for disease activity, disease stage, medication, and laboratory findings. Serum concentrations of the following parameters were measured: IL-1ß, IL-6, IL-17 A, IL-17 F, IL-21, IL-22, IL-23, TNF-α, sCD40L, IL-4, IL-10, IL-25, IL-31, IL-33, and INF-γ. A total number of 62 AAV subjects was included in the study (39 females; 23 males). Forty-five subjects were PR3+, 17 subjects showed ANCA specificity for MPO. The majority of all cytokines fell under the lower detection limit of the assay. Serum IL-10 was higher in both, AAV and SSc as compared to controls; it was also higher in early systemic AAV. Serum IL-33 was elevated in AAV and SSc; in AAV, higher levels were found in non-necrotizing GN and RTX untreated subjects. Serum CD40L was raised in AAV as well; higher concentrations were also found in PR3+ and MPO+ patients and early systemic, generalized, and refractory AAV. IL-10 may potentially serve as a marker of early systemic AAV. IL-33 may help to identify subjects with a higher risk for necrotizing GN in AAV.

Individualised Homeopathic Therapy in ANCA Negative Rapidly Progressive Necrotising Crescentic Glomerulonephritis with Severe Renal Insufficiency - A Case Report.

Anti-Neutrophil Cytoplasmic Antibody (ANCA)-negative Rapidly Progressive Glomerulonephritis (RPGN) is a severe form of autoimmune renal injury with a bleak prognosis. A 60-year-old Indian woman was treated with classical homeopathy for ANCA-negative RPGN, and after one year of treatment, serum creatinine and other parameters indicating renal injury dropped steadily despite the withdrawal of immunosuppressive drugs; renal dialysis, which was conducted twice a week initially, was made rarer and stopped after one year. Classical homeopathy may be considered a potential therapeutic modality in severe pathologies. Controlled studies are required to establish further the extent to which classical homeopathy may relieve patients from procedures such as dialysis that cause considerable physical and economic discomfort.

Long-Term Outcomes of Patients With HCV-Associated Cryoglobulinemic Vasculitis After Virologic Cure.

Patients with hepatitis C virus-associated cryoglobulinemic vasculitis (HCV-CV) have high rates of clinical remission after treatment with direct-acting antivirals (DAAs), but circulating cryoglobulins persist, and vascular disorders reappear in some patients shortly after DAA treatment ends. We performed a prospective study to assess the long-term clinical and immune system effects of HCV eradication with DAAs in 46 patients with HCV-CV and 42 asymptomatic patients with circulating cryoglobulins. A median of 24 months after DAA treatment (range, 17-41 months), 66% of patients with HCV-CV and 70% of asymptomatic patients with circulating cryoglobulins had an immunologic response, with comparable reductions in cryocrit from 2.6% to 0% (P < .05). However, 20% of patients still had positive test results for cryoglobulins after DAA therapy. Among patients with HCV-CV, 42 (91%) had a clinical response, in that their Birmingham Vasculitis Activity Score (version 3) decreased from 7 to 0 (P < .01). Nevertheless, within 2 years after a sustained viral response to DAA therapy, 5 patients with HCV-CV (11%, 4 with cirrhosis) had relapses of vasculitis that included severe organ damage and death.

Granulomatosis with polyangiitis: clinical course and outcome of 60 patients from a single center in South India.

Granulomatosis with polyangiitis (GPA) previously known as Wegener's granulomatosis is one of the forms of idiopathic systemic vasculitis. There is very scanty data available on GPA in Asian and Indian population. We studied data of 60 patients from southern India, diagnosed with GPA to describe the physical characteristics, the treatment, and outcome. Patients who fulfilled any two of the four criteria proposed by the American College of Rheumatology, and those with clinical features of GPA with ANCA positivity and histopathological confirmation, were included in the study. Disease activity and damage were assessed by Birmingham Vasculitis Activity Score v. 3 (BVAS v. 3) and Vasculitis Damage Index (VDI), respectively. Relapses were defined as recurrence of GPA of sufficient severity to require treatment or increase in the dose of treatment on a patient who was previously stable. Out of 60 patients, initial BVAS evaluation showed that 57 (95%) patients had severe disease and 3 (5%) patients had limited disease where median BVAS was 21.5 (range 17-44). Follow-up BVAS evaluation for severe disease showed that 13 (22.8%) patients continued with severe disease of which 9 patients did not survive, 24 (42.3%) had remission, 11 (19.2%) had persistent disease, and 9 (15.7%) were lost to follow-up. The mean VDI score was 2.5 ± 2. Renal involvement was established in 42 (70%) patients. Upper and lower respiratory involvement was seen in 38 (63%) patients. Nervous system involvement was noted in the 15 (25%) patients. Articular manifestations were seen in 16 (27%) patients. Diverse clinical manifestation delay early diagnosis and treatment of this potentially treatable vasculitis. Focused approach could expedite early diagnosis and can reduce the mortality.

The BVAS is an independent predictor of cardiovascular events and cardiovascular disease-related mortality in patients with ANCA-associated vasculitis: A study of 504 cases in a single Chinese center.

BACKGROUND: Cardiovascular diseases (CVD) are the major causes of death in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) during long-term follow-up. This study investigated risk factors for cardiovascular events (CVE) and CVD-related mortality in Chinese AAV patients. METHODS: Five hundred and four AAV patients in our center were retrospectively included. The predictive value of variables associated with CVE- and CVD-related mortality were analyzed. RESULTS: During follow-up of a median duration of 38 (range 1-228) months, 117 out of 504 patients had CVE. Independent predictors of CVE were age [increase by 10 years, hazard ratio (HR) 1.436, 95% confidence interval (CI) 1.187-1.736, p = 0.000], systolic blood pressure (increase by 10mmHg, HR = 1.171, 95% CI: 1.038-1.321, p = 0.010), estimated glomerular filtration rate (eGFR) (increase by 1mL/min/1.73m2, HR = 0.992, 95% CI: 0.984-0.999, p = 0.020), high-density lipoprotein level (HR = 0.530, 95% CI: 0.303-0.926, p = 0.026) and the Birmingham Vasculitis Activity Score (BVAS) (HR = 1.039, 95% CI: 1.011-1.067, p = 0.006). Forty-one patients died from CVD. Independent predictors of CVD-related mortality were age (increase by 10 years; HR = 1.732, 95% CI: 1.237-2.426, p = 0.001), eGFR (increase by 1mL/min/1.73m2, HR = 0.984, 95% CI: 0.970-0.997, p = 0.016), pre-existing CV disease (HR = 2.872, 95% CI: 1.503-5.487, p = 0.001) and BVAS (HR = 1.064, 95% CI: 1.018-1.113, p = 0.006). We further analyzed CVE- and CVD-related mortality after 2 years since diagnosis, and found BVAS were still an independent predictor of CVE- and CVD-related mortality. CONCLUSION: Besides the traditional risk factors, BVAS at presentation was an independent predictor of CVE- and CVD-related mortality in patients with AAV.

Clinical characteristics and long-term survival differences of the ANCA-associated vasculitis group: a cross-sectional study of 27 patients.

OBJECTIVE: The goal of this study was to describe long-term patient survival and possible prognostic factors of a group of patients diagnosed with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) hospitalized at the tertiary Rheumatology Centre in Vilnius. MATERIAL AND METHODS: A cross-sectional study of 27 patients hospitalized at the Rheumatology Centre of Santaros klinikos of Vilnius University Hospital from 1 January 2001 to 31 December 2015 with diagnoses of GPA and MPA were carried out. Data on demographics, clinical characteristics, laboratory data, and the Birmingham Vasculitis Activity Score were collected. RESULTS: Seven (25.9%) patients during the onset of the disease received only oral glucocorticoids and 20 (74.1%) patients took additional medication. The BVAS median was 7 (minimum [min] - 2; maximum [max] - 23). The age median was 52 years (min - 12; max - 75). The overall mortality rate was 18.5%. Mean survival time was 126.6 months (95% confidence interval [CI] = 104.5 to 148.6) limited to 154.6 months for the longest-surviving patient. CONCLUSIONS: Life expectancy during past 15 years for AAV patients increased from 99.4 to 126.6 months. A high BVAS score at the onset of the disease is a bad prognostic factor related to shorter life expectancy. The growth of Staphylococcus aureus from nasopharynx might be associated with higher mortality rates and relapses in AAV patients.

Birmingham vasculitis activity score of more than 9.5 at diagnosis is an independent predictor of refractory disease in granulomatosis with polyangiitis.

AIM: We investigated whether clinical manifestations, anti-neutrophil cytoplasmic antibodies (ANCAs), Birmingham vasculitis activity score (BVAS) for granulomatosis with polyangiitis (GPA) and five factor score (FFS) at diagnosis can predict relapse or refractory disease in 30 histology-proven GPA patients with follow-up duration ≥ 12 weeks. METHODS: We reviewed the medical records of 30 GPA patients. We collected clinical data, ANCAs, BVAS for GPA, FFSs at diagnosis, and we compared variables between the two groups based on relapse or refractory disease. The optimal cut-offs were extrapolated. Multivariate logistic regression and Cox hazard model analyses were conducted to identify predictors of refractory disease. RESULTS: The mean age and follow-up duration of patients were 63.3 years old and 45.2 months. The mean initial BVAS for GPA, FFS (1996) and FFS (2009) were 5.4, 0.6 and 1.0. There were no significant predictors of relapse. The mean BVAS for GPA, FFS (1996) and FFS (2009) of patients with refractory disease were higher than those without (P < 0.05 for all). Patients having BVAS for GPA ≥ 9.5, FFS (1996) ≥ 2 and FFS (2009) ≥ 2 exhibited significantly enhanced risk of refractory disease than those without (relative risk 23.0, 11.0, and 55.0, respectively), and low cumulative refractory disease-free survival rates. Multivariate Cox hazard model analysis proved BVAS for GPA ≥ 9.5 was an independent predictor of refractory disease during the follow-up duration (odds ratio 12.892). CONCLUSION: BVAS for GPA ≥ 9.5 was an independent predictor of refractory disease during follow-up duration ≥ 12 weeks.

Simple, readily available clinical indices predict early and late mortality among patients with ANCA-associated vasculitis.

BACKGROUND: The early identification of patients with ANCA-associated vasculitis (AAV) who are at increased risk for inferior clinical outcome at the time of diagnosis might help to optimize the immunosuppressive therapy. In this study we wanted to determine the predictive value of simple clinical characteristics, which may be applicable for early risk-stratification of patients with AAV. METHODS: We retrospectively analyzed the outcome of 101 consecutive patients with AAV receiving a protocolized immunosuppressive therapy. Baseline Birmingham Vasculitis Activity Score (BVAS) and non-vasculitic comorbidities were computed, then predictors of early (<90 days) and late (>90 days) mortality, infectious death, relapse and end stage kidney disease (ESKD) were evaluated. RESULTS: The baseline comorbidity score independently predicted early mortality (HR 1.622, CI 1.006-2.614), and showed association with infectious mortality (HR 2.056, CI 1.247-3.392). Patients with BVAS at or above median (=21) had worse early mortality in univariable analysis (HR 3.57, CI 1.039-12.243) (p = 0.031), and had more frequent relapses (p = 0.01) compared to patients with BVAS below median. CONCLUSIONS: Assessing baseline comorbidities, beside clinical indices characterizing the severity and extension of AAV, might help clinicians in risk-stratification of patients. Future prospective studies are needed to investigate whether therapies based on risk-stratification could improve both short term and long term survival.

Liver involvement in ANCA-associated vasculitis.

The aim of the study was to investigate the incidence, the clinical course and outcome of liver involvement and autoimmune hepatic diseases in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Liver function tests (LFT) (i.e. aspartate and alanine aminotransferase [AST, ALT], gamma-glutamyl transpeptidase [gamma-GT], alkaline phosphatase [ALP] and total bilirubin) were analysed at disease onset in therapy-naïve patients and during remission in patients with granulomatosis with polyangiitis (GPA, n = 67), microscopic polyangiitis (MPA, n = 28) and eosinophilic granulomatosis with polyangiitis (EGPA, n = 14). Results were correlated to the Birmingham Vasculitis Activity Score version 3 (BVAS v.3). Also, serologic tests for other autoimmune hepatic diseases were performed in these patients. During the active state, LFT abnormalities could be detected in 54 AAV patients (49.4 %). ALT, gamma-GT and ALP were significantly higher in GPA patients compared to MPA or EGPA patients at disease onset (p < 0.05). Increased values for gamma-GT in GPA patients correlated with the BVAS (p < 0.01) and were associated with pulmonary involvement, pulmonary-renal syndrome and a longer time to remission. Increased LFT in GPA patients decreased subsequently towards normal levels after initiation of therapy (p < 0.01). No case of severe liver involvement or autoimmune hepatic liver diseases was found in AAV patients. Liver involvement was mainly restricted to GPA patients, is associated with the disease activity and indicates a poorer outcome in patients with GPA. Progressive liver involvement or autoimmune hepatic diseases were not observed.

Comparison of a novel chemiluminescence enzyme immunoassay (CLEIA) with enzyme-linked immunosorbent assay (ELISA) for the determination of MPO-ANCA in patients with ANCA-associated vasculitis.

BACKGROUND: Myeloperoxidase (MPO) anti-neutrophil cytoplasmic antibody (ANCA) represents the serological hallmark of ANCA-associated vasculitis (AAV). We evaluated the analytical and diagnostic accuracy of chemiluminescence enzyme immunoassay (CLEIA) versus enzyme-linked immunosorbent assay (ELISA) for the detection of MPO-ANCA. METHODS: A total of 242 sera obtained from 51 patients with AAV and 103 patients without AAV were tested for MPO-ANCA by ELISA (NephroScholor MPOANC II) and CLEIA (the STACIA MEBLux test). Disease activity in the patients with AAV was determined based on the Birmingham Vasculitis Activity Score. We analyzed the correlations between the MPO-ANCA titers determined by the CLEIA and those determined by the ELISA, and also between the MPO-ANCA titers and the disease activity. RESULTS: The MPO-ANCA titers determined by the CLEIA (x) were strongly correlated with those determined by the ELISA (y). The correlation could be expressed by the following equation in this study: y = 1.8x + 7.7 (r = 0.96; p < 0.0001). At the cutoff value of 3.5 U/ml, the CLEIA yielded positive test results for MPO-ANCA in 73 of the 242 sera (30.2%), while at the cutoff value of 20 U/ml, ELISA yielded positive test results in 57 of the 242 sera (23.6%). The CLEIA yielded false-positive test results in 4 of the 120 sera obtained from the non-AAV patients (3.3%), whereas the ELISA yielded a false-positive result in only 1 of the 120 sera obtained from the non-AAV patients (0.8%). The sensitivity and specificity of the CLEIA for the diagnosis of AAV were 100% and 96.7%, respectively, while those of the ELISA were 94.3% and 99.2%, respectively. The sensitivity and specificity of the CLEIA for the prediction of active disease were 100% and 64.4%, respectively, while those of the ELISA were 94.3% and 73.6%, respectively. CONCLUSION: The false positivity rate of the CLEIA for MPO-ANCA tended to be high as compared with that of the ELISA. Also, according to the correlation coefficient between the results of the CLEIA and the ELISA calculated in this study, it is necessary to pay attention to the differences in the sensitivity and specificity between CLEIA and ELISA.

Antineutrophil cytoplasmic antibody-associated renal vasculitis treated with autologous mesenchymal stromal cells: evaluation of the contribution of immune-mediated mechanisms.

We report the first case of renal antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis treated with autologous mesenchymal stromal cells (MSCs). A 73-year-old man was admitted to the hospital for malaise, weight loss, and oliguria. His serum creatinine level was 2.7 mg/dL but it rapidly increased to 7.8 mg/dL; urinalysis showed proteinuria and hematuria, and the ANCA to myeloperoxidase with a perinuclear pattern (pANCA) titer was high (132 IU/mL). Renal biopsy showed necrotizing crescentic glomerulonephritis. Standard immunosuppressive therapy (cyclophosphamide and corticosteroids) was ineffective. Rituximab therapy was started, but it was discontinued after the third dose to minimize the risk of systemic spread of a severe oral Candida infection and to prevent superinfections that were facilitated by leukopenia. The patient received autologous MSCs, 1.5 × 10(6) cells/kg body weight, intravenously. After 7 days, his serum creatinine level decreased to 2.2 mg/dL, pANCA titer decreased to 75 IU/mL, and urinalysis findings normalized. Eight months later, he received a second MSC infusion because his serum creatinine level increased. In 1 week, his creatinine level decreased to 1.9 mg/dL and his pANCA titer decreased to 14 IU/mL. Immunosuppressive therapy was subsequently withdrawn. At the last follow-up visit, 12 months after the second MSC infusion, the patient remained in clinical remission without any therapy. Infusion of MSCs induced expansion of the T-lymphocyte subset expressing a regulatory T-cell phenotype (CD4(+)CD25(+)Foxp3(+)) and a notable reduction in interferon-γ, interleukin 6, and tumor necrosis factor serum levels.

Hepatotropic viral infection associated systemic vasculitides-hepatitis B virus associated polyarteritis nodosa and hepatitis C virus associated cryoglobulinemic vasculitis.

Two hepatotropic viruses have been shown to have causal relationship with systemic vasculitis-hepatitis B with classical polyarteritis nodosa and hepatitis C with cryoglobulinemic vasculitis. The present paper provides an updated overview on the clinical presentations and management of these vasculitides. HBV associated PAN patients have higher weight loss, peripheral neuropathy, mononeuritis multiplex, abdominal pain, gastrointestinal manifestations requiring surgery, cardiomyopathy, orchitis, hypertension, and/or elevated transaminase levels. Microaneurysms are also more common in mesenteric artery. Skin manifestations, however are less common. These patients also have a severe disease as suggested by higher five factor score and higher BVAS. Though relapses are less common, mortality is higher in patients with HBV PAN as compared to non HBV PAN. Plasmapheresis has a role in treatment in clearing off immune complexes. The common clinical manifestations of HCV associated cryoglobulinemic vasculitis are skin lesions, peripheral neuropathy, glomerulonephritis, arthritis, and sicca symptoms. Though combination therapy comprising of pegylated interferon α and ribavirin is the first line of management, immunotherapy is needed for severe or life threatening manifestations. Recent randomized trials have shown the efficacy of rituximab in such situations.