Co-existence of ANCA-associated vasculitides with immune-mediated diseases: a single-center observational study.

BACKGROUND: Antineutrophil cytoplasmic antibody-associated vasculitides (AAV) is a group of systemic necrotizing small vessel autoimmune diseases, with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) being the two most common. The co-existence of AAV with different immune-mediated diseases (autoimmune disesases - AID) might affect the clinical presentation of the primary disease. The purpose of the study was to assess the co-existence of AAV with AID and to investigate whether it affects the characteristics and the course of AAV. METHODS: A retrospective single-center study was performed to identify patients with a diagnosis of MPA or GPA and concomitant AID, and to investigate their clinical features and characteristics. The group consisted of consecutive unselected AAV patients treated at a large university-based hospital, since 1988 with follow-up until 2022. RESULTS: Among 284 patients diagnosed either with GPA (232) or MPA (52), 40 (14,1%) had co-existing AIDs. The most frequent were: Hashimoto thyroiditis (16 cases), rheumatoid arthritis (8 cases), followed by psoriasis (6 cases), pernicious anemia (3 cases), and alopecia (3 cases). Patients with autoimmune comorbidities had a significantly longer time between the onset of symptoms and the diagnosis (26 vs. 11 months, p < 0.001). Laryngeal involvement (20.0% vs. 9.0%, p = 0,05), peripheral nervous system disorders (35.0% vs. 13.9%, p < 0.001), and neoplasms (20.0% vs. 8.6%, p = 0,044) were more common in patients with AID comorbidities, compared to subjects without AID. In contrast, renal involvement (45.0% vs. 70.9%, p = 0.001) and nodular lung lesions (27.5% vs. 47.5%, p = 0.044) were significantly less frequent in patients with co-morbidities. Following EUVAS criteria, patients with autoimmune co-morbidities had a generalized form of the disease without organ involvement (52.5% vs. 27.2%, p = 0.007), while the others had a higher percentage of generalized form with organ involvement (38.3% vs. 20.0%, p = 0.007). CONCLUSIONS: The coexistence of AAV with different autoimmune diseases is not common, but it might affect the clinical course of the disease. Polyautoimmunity prolonged the time to diagnosis, but the AAV course seemed to be milder. Particular attention should be paid to the increased risk of cancer in these patients. It also seems reasonable that AAV patients should receive a serological screening to exclude the development of overlapping diseases.

Predictive utility of ANCA positivity and antigen specificity in the assessment of kidney disease in paediatric-onset small vessel vasculitis.

OBJECTIVES: The objective of this study is to evaluate whether anti-neutrophil cytoplasmic antibody (ANCA) seropositivity and antigen specificity at diagnosis have predictive utility in paediatric-onset small vessel vasculitis. METHODS: Children and adolescents with small vessel vasculitis (n=406) stratified according to the absence (n=41) or presence of ANCA for myeloperoxidase (MPO) (n=129) and proteinase-3 (PR3) (n=236) were compared for overall and kidney-specific disease activity at diagnosis and outcomes between 1 and 2 years using retrospective clinical data from the ARChiVe/Paediatric Vasculitis Initiative registry to fit generalised linear models. RESULTS: Overall disease activity at diagnosis was higher in PR3-ANCA and MPO-ANCA-seropositive individuals compared with ANCA-negative vasculitis. By 1 year, there were no significant differences, based on ANCA positivity or specificity, in the likelihood of achieving inactive disease (~68%), experiencing improvement (≥87%) or acquiring damage (~58%). Similarly, and in contrast to adult-onset ANCA-associated vasculitis, there were no significant differences in the likelihood of having a relapse (~11%) between 1 and 2 years after diagnosis. Relative to PR3-ANCA, MPO-ANCA seropositivity was associated with a higher likelihood of kidney involvement (OR 2.4, 95% CI 1.3 to 4.7, p=0.008) and severe kidney dysfunction (Kidney Disease Improving Global Outcomes (KDIGO) stages 4-5; OR 6.04, 95% CI 2.77 to 13.57, p<0.001) at onset. Nonetheless, MPO-ANCA seropositive individuals were more likely to demonstrate improvement in kidney function (improved KDIGO category) within 1 year of diagnosis than PR3-ANCA seropositive individuals with similarly severe kidney disease at onset (p<0.001). CONCLUSIONS: The results of this study suggest important paediatric-specific differences in the predictive value of ANCA compared with adult patients that should be considered when making treatment decisions in this population.

Kidney Failure in Pauci-immune Crescentic Glomerulonephritis: Rationale for Immunosuppression to Improve Kidney Outcome.

PURPOSE OF REVIEW: Pauci-immune crescentic glomerulonephritis is the hallmark finding in ANCA-associated vasculitis (AAV) when the kidneys are affected. The rationale for immunosuppression in AAV is based on the underlying autoimmune nature of the disease. Overall remission rates, kidney outcomes, and the burden of disease have greatly improved since the discovery of various immunosuppressive therapies, but relapses remain common, and a significant proportion of patients continue to progress to end-stage kidney disease. Here, we review the role of immunosuppressive therapies for the treatment of pauci-immune crescentic glomerulonephritis. RECENT FINDINGS: Besides the recognized role of B and T cells in the pathogenies of AAV, the focus on the contribution of inflammatory cytokines, neutrophil extracellular traps (NETs), and the complement system allowed the discovery of new therapies. Specifically, the C5a receptor blocker (avacopan) has been approved as a glucocorticoid-sparing agent. Additionally, based on observational data, more clinicians are now using combination therapies during the induction phase. There is also an evolving understanding of the role of plasma exchange in removing ANCA antibodies. Furthermore, the recent development of risk score systems provides physicians with valuable prognostic information that can influence decisions on immunosuppression, although future validation from larger cohorts is needed. The over-activation of various immune pathways plays a significant role in the pathogenesis of pauci-immune crescentic glomerulonephritis in AAV. Immunosuppression is, therefore, an important strategy to halt disease progression and improve overall outcomes. Relapse prevention while minimizing adverse events of immunosuppression is a major long-term goal in AAV management.

Pathogenesis of Pulmonary Manifestations in ANCA-Associated Vasculitis and Goodpasture Syndrome.

Pulmonary manifestations of vasculitis are associated with significant morbidity and mortality in affected individuals. They result from a complex interplay between immune dysregulation, which leads to vascular inflammation and tissue damage. This review explored the underlying pathogenesis of pulmonary involvement in vasculitis, encompassing various forms such as granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA), and anti-GBM disease. Mechanisms involving ANCA and anti-GBM autoantibodies, neutrophil activation, and neutrophil extracellular trap (NETs) formation are discussed, along with the role of the complement system in inducing pulmonary injury. Furthermore, the impact of genetic predisposition and environmental factors on disease susceptibility and severity was considered, and the current treatment options were presented. Understanding the mechanisms involved in the pathogenesis of pulmonary vasculitis is crucial for developing targeted therapies and improving clinical outcomes in affected individuals.

Proteinase 3-specific antineutrophil cytoplasmic antibody-associated vasculitis.

Proteinase 3 (PR3)-specific antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is one of two major ANCA-associated vasculitis variants and is pathogenically linked to granulomatosis with polyangiitis (GPA). GPA is characterised by necrotising granulomatous inflammation that preferentially affects the respiratory tract. The small vessel vasculitis features of GPA are shared with microscopic polyangiitis. Necrotising granulomatous inflammation of GPA can lead to PR3-ANCA and small vessel vasculitis via activation of neutrophils and monocytes. B cells are central to the pathogenesis of PR3-ANCA-associated vasculitis. They are targeted successfully by remission induction and maintenance therapy with rituximab. Relapses of PR3-ANCA-associated vasculitis and toxicities associated with current standard therapy contribute substantially to remaining mortality and damage-associated morbidity. More effective and less toxic treatments are sought to address this unmet need. Advances with cellular and novel antigen-specific immunotherapies hold promise for application in autoimmune disease, including PR3-ANCA-associated vasculitis. This Series paper describes the inter-related histopathological and clinical features, pathophysiology, as well as current and future targeted treatments for PR3-ANCA-associated vasculitis.

Investigating the concomitance of anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitides and inflammatory bowel disease (IBD).

OBJECTIVE: To assess relationship between Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis and inflammatory bowel disease (IBD). METHODS: This is a retrospective study design. The patients were identified using a preset criteria of patients who have the diagnosis of ANCA associated vasculitis including a diagnosis of granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) or eosinophilic granulomatosis with polyangiitis (EGPA) with overlapping inflammatory bowel disease (Crohn's disease or ulcerative colitis) in the time period from 01/01/2020 to 08/03/2023. Subsequently data from each patient was collected that will include baseline demographics, disease characteristics, disease activity, treatment information, multiorgan involvement, and pathology findings which were then analyzed. RESULTS: 39 patients were identified that met criteria. 20 patients carried a diagnosis of GPA, 6 had MPA and 4 patients had EGPA. 20 patients with GPA had inflammatory bowel disease, 13 with ulcerative colitis and 6 with Crohn's disease while 1 GPA patient had unspecified inflammatory bowel disease. 4 patients with EGPA had inflammatory bowel disease, 2 with ulcerative colitis and 2 with Crohn's disease. 6 patients with MPA had inflammatory bowel disease, 4 with ulcerative colitis and 2 with Crohn's disease. IBD diagnosis preceded the diagnosis of ANCA vasculitis in 77.8 % of the cases. CONCLUSION: Objective observation and deductions from this study raise the concern for a possible pathogenic association of ANCA associated vasculitis and inflammatory bowel disease and more research is needed to identify any causal association or influence of the two systemic disease on each other.

Myeloperoxidase-specific antineutrophil cytoplasmic antibody-associated vasculitis.

Myeloperoxidase (MPO)-specific antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (MPO-ANCA-associated vasculitis) is one of two major ANCA-associated vasculitis variants characterised by systemic necrotising vasculitis with few or no immune deposits. MPO-ANCA-associated vasculitis predominantly affects small blood vessels and, in contrast to its counterpart proteinase 3-ANCA-associated vasculitis, is generally not associated with granulomatous inflammation. The kidneys and lungs are the most commonly affected organs. The pathogenesis of MPO-ANCA-associated vasculitis is characterised by loss of tolerance to the neutrophil enzyme MPO. This loss of tolerance leads to a chronic immunopathological response where neutrophils become both the target and effector of autoimmunity. MPO-ANCA drives neutrophil activation, leading in turn to tissue and organ damage. Clinical trials have improved the therapeutic approach to MPO-ANCA-associated vasculitis. However, there remains substantial unmet need regarding relapse frequency, toxicity of current treatment, and long-term morbidity. In this Series paper, we present the current state of research regarding pathogenesis, diagnosis, and treatment of MPO-ANCA-associated vasculitis.

Transcription factor Nrf2 activation regulates NETosis, endothelial injury, and kidney disease in myeloperoxidase-positive antineutrophil cytoplasmic antibody-associated vasculitis.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systemic autoimmune disease pathologically characterized by vascular necrosis with inflammation. During AAV development, activated neutrophils produce reactive oxygen species (ROS), leading to the aberrant formation of neutrophil extracellular traps (NETs) via NETosis and subsequent fibrinoid vascular necrosis. Nuclear factor-erythroid 2-related factor 2 (Nrf2) functions as an intracellular defense system to counteract oxidative stress by providing antioxidant properties. Herein, we explored the role of Nrf2 in the pathogenesis of AAV. The role and mechanism of Nrf2 in ANCA-stimulated neutrophils and subsequent endothelial injury were evaluated in vitro using Nrf2 genetic deletion and Nrf2 activator treatment. In corresponding in vivo studies, the role of Nrf2 in ANCA-transfer AAV and spontaneous AAV murine models was examined. Pharmacological activation of Nrf2 in vitro suppressed ANCA-induced NET formation via the inhibition of ROS. In contrast, NET formation was enhanced in Nrf2-deficient neutrophils. Furthermore, Nrf2 activation protected endothelial cells from ANC-induced NETs-mediated injury. In vivo, Nrf2 activation ameliorated glomerulonephritis in two AAV models by upregulating antioxidants and inhibiting ROS-mediated NETs. Furthermore, Nrf2 activation restrained the expansion of splenic immune cells, including T lymphocytes and limited the infiltration of Th17 cells into the kidney. In contrast, Nrf2 genetic deficiency exacerbated vasculitis in a spontaneous AAV model. Thus, the pathophysiological process in AAV may be downregulated by Nrf2 activation, potentially leading to a new therapeutic strategy by regulating NETosis.

Clinical phenotype of AAV, anti-GBM disease and double-positive patients after SARS-CoV-2 vaccination.

The number of anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV), anti-glomerular basement membrane (GBM) disease and double-positive patients (DPPs) following the coronavirus disease 2019 (COVID-19) vaccine reported in the literature is increasing, we reviewed the reported cases of AAV, anti-GBM disease and DPPs subsequent to COVID-19 vaccination, and compared the disparities in DPPs who received the COVID-19 vaccination and those who did not. We did not observe any differences in clinical phenotype of AAV, anti-GBM disease and DPPs before and after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination.

Protective effect of astaxanthin on ANCA-associated vasculitis.

OBJECTIVE: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systemic autoimmune disease characterized by inflammation and fibrinoid necrosis of medium and small vessels, and its pathogenesis is closely related to inflammation and oxidative stress. Astaxanthin (ATX) is a carotenoid with anti-inflammatory, antioxidant, and immunomodulatory effects. We hypothesized that ATX could play a role in AAV treatment. This study aimed to investigate whether ATX has a protective effect against AAV and to elucidate its regulatory mechanism. METHODS: In vitro experiments, neutrophils isolated from healthy people were treated with ATX or not and cultured with serum from myeloperoxidase (MPO) -ANCA-positive patients and healthy persons. The levels of IL-6 and TNF-α in neutrophil culture supernatant before and after stimulation were measured. Neutrophil extracellular traps (NETs) and intracellular reactive oxygen species (ROS) in neutrophils were detected after stimulation. In vivo study, experimental autoimmune vasculitis (EAV) rat models were established and then treated with ATX via intragastric administration for 6 consecutive weeks. Urinary erythrocytes, urinary proteins, and serum creatinine were detected and HE staining was performed to assess renal injury in rats. Lung hemorrhage was observed by gross dissection and microscopic Prussian blue staining. The level of serum MPO-ANCA was detected. Serum IL-6, TNF-α, superoxide dismutase (SOD), and glutathione peroxidase (GSH-px) in rats were measured to explore the effects of ATX on oxidative stress and inflammation in EAV rats. The deposition of MPO in kidney and lung of rats was detected by immunohistochemistry. RESULTS: ATX significantly inhibited neutrophil secretion of inflammatory factors IL-6 and TNF-α. ATX reduced the elevated levels of ROS in neutrophils stimulated by serum from AAV patients and alleviated the release of NETs. ATX administration was observed to reduce the degree of hematuria, proteinuria, and glomerular crescent formation in EAV rats. The degree of pulmonary hemorrhage was significantly reduced. Besides, the serum levels of IL-6 and TNF-α were attenuated, and antioxidant SOD and GSH-px increased in serum. Pathological results showed that MPO deposition was decreased in lung and kidney tissues after ATX treatment. CONCLUSION: ATX could ameliorate the organ damages in EAV rats. It could serve as a hopeful therapy for AAV by its anti-inflammatory and anti-oxidative feature as a unique nature carotenoid.

Overlap syndrome of systemic sclerosis with antineutrophil cytoplasmic antibody-associated vasculitis according to 2022 ACR/EULAR criteria.

BACKGROUND/AIMS: This study applied the 2022 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) criteria for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) to patients with systemic sclerosis (SSc) and investigated the frequency of overlap syndrome of SSc and AAV (SSc-AAV-OS). METHODS: Among the 232 patients diagnosed with SSc, 105 with signs suggestive of small- or medium-vessel vasculitis, which were defined as the present of interstitial lung disease (ILD), peripheral neuropathy, or suspected renal vasculitis, were included in this study and analyzed. RESULTS: Among the 105 SSc patients, the detection rate of ANCA was 19.0%. When the 2022 ACR/EULAR criteria were applied, the frequency of SSc-AAV-OS was 20.0%, which was much higher than 1.7% reported with previous criteria for AAV. ANCA positivity contributed to the reclassification of SSc-AAV-OS more than ANCA negativity in SSc patients with signs suggestive of small- or medium-vessel vasculitis. CONCLUSION: The frequency of SSc-AAV-OS in SSc patients with signs suggestive of small- or medium-vessel vasculitis at diagnosis was 20.0%. Therefore, we suggest that physicians should perform ANCA tests in SSc patients exhibiting signs suggestive of small- or medium-vessel vasculitis and apply the new criteria for AAV.

The role of anti-HMGB1 antibody and anti-moesin antibody in ANCA-associated vasculitis / Papel de los anticuerpos anti-HMGB1 y antimoesina en la vasculitis asociada a ANCA

Objective The study aims to evaluate the role of anti-high mobility group box 1 (HMGB1) antibody and anti-moesin antibody in the diagnosis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and its possible relationship with the different clinical manifestations. Methods The study involved 60 AAV patients, 58 patients with autoimmune disease other than AAV and 50 healthy subjects. The serum levels of anti-HMGB1 and anti-moesin antibodies were determined by enzyme-linked immunosorbent assay (ELISA), and the second determination was made 3 months after treatment of AAV patients. Results Serum levels of anti-HMGB1 and anti-moesin antibodies in AAV group were significantly higher than those in non-AAV group and HC group. The area under the curve (AUC) of anti-HMGB1 and anti-moesin in diagnosing AAV were 0.977 and 0.670, respectively. Anti-HMGB1 levels were significantly elevated in AAV patients with pulmonary involvement, while the concentrations of anti-moesin were significantly increased in patients with renal damage. Anti-moesin were positively correlated with BVAS (r=0.261, P=0.044), creatinine (r=0.296, P=0.024) and negatively correlated with complement C3 (r=−0.363, P=0.013). Besides, anti-moesin levels of active AAV patients were significantly higher than those in inactive patients. The concentrations of serum anti-HMGB1 could be significantly decreased after induction remission treatment (P<0.05). Conclusion Anti-HMGB1 and anti-moesin antibodies play important roles in the diagnosis and prognosis of AAV, which may act as potential disease markers for AAV (AU)

Objetivo El estudio tiene como objetivo evaluar el papel del anticuerpo antigrupo de alta movilidad box 1 (HMGB1) y el anticuerpo antimoesina en el diagnóstico de la vasculitis asociada (VAA) a anticuerpos citoplasmáticos antineutrófilos (ANCA) y su posible relación con las diferentes manifestaciones clínicas. Métodos En el estudio participaron 60 pacientes con VAA, 58 pacientes con enfermedad autoinmune distinta de la VAA y 50 sujetos sanos. Los niveles séricos de anticuerpos anti-HMGB1 y antimoesina se determinaron mediante ensayo inmunoabsorbente ligado a enzimas (ELISA), y la segunda determinación se realizó tres meses después del tratamiento de pacientes con VAA. Resultados Los niveles séricos de anticuerpos anti-HMGB1 y antimoesina en el grupo AAV fueron significativamente más altos que los del grupo sin VAA y el grupo control sanitario. El área bajo la curva (AUC) de anti-HMGB1 y antimoesina en el diagnóstico de VAA fueron 0,977 y 0,670, respectivamente. Los niveles de anti-HMGB1 se elevaron significativamente en pacientes con VAA con afectación pulmonar, mientras que las concentraciones de antimoesina aumentaron significativamente en pacientes con daño renal. La antimoesina se correlacionó positivamente con puntuación de actividad vascular de Birmingham (r=0,261, p=0,044), creatinina (r=0,296, p=0,024) y se correlacionó negativamente con el complemento C3 (r=−0,363, p=0,013). Además, los niveles de antimoesina de los pacientes activos con VAA fueron significativamente más altos que los de los pacientes inactivos. Las concentraciones séricas de anti-HMGB1 podrían disminuir significativamente después del tratamiento de remisión de inducción (p<0,05). Conclusión Los anticuerpos anti-HMGB1 y antimoesina juegan un papel importante en el diagnóstico y pronóstico de VAA, que pueden actuar como marcadores potenciales de enfermedad para VAA (AU)

Stratified genetic analysis reveals sex differences in MPO-ANCA-associated vasculitis.

OBJECTIVE: To identify and genetically characterize subgroups of patients with ANCA-associated vasculitides (AAV) based on sex and ANCA subtype. METHODS: A previously established SNP dataset derived from DNA sequencing of 1853 genes and genotyping of 1088 Scandinavian cases with AAV and 1589 controls was stratified for sex and ANCA subtype and analysed for association with five top AAV SNPs. rs9274619, a lead variant at the HLA-DQB1/HLA-DQA2 locus previously associated with AAV positive for myeloperoxidase (MPO)-ANCA, was analysed for association with the cumulative disease involvement of ten different organ systems. RESULTS: rs9274619 showed a significantly stronger association to MPO-ANCA-positive females than males [P = 2.0 × 10-4, OR = 2.3 (95% CI 1.5, 3.5)], whereas proteinase 3 (PR3)-ANCA-associated variants rs1042335, rs9277341 (HLA-DPB1/A1) and rs28929474 (SERPINA1) were equally associated with females and males with PR3-ANCA. In MPO-ANCA-positive cases, carriers of the rs9274619 risk allele were more prone to disease engagement of eyes [P = 0.021, OR = 11 (95% CI 2.2, 205)] but less prone to pulmonary involvement [P = 0.026, OR = 0.52 (95% CI 0.30, 0.92)]. Moreover, AAV with both MPO-ANCA and PR3-ANCA was associated with the PR3-ANCA lead SNP rs1042335 [P = 0.0015, OR = 0.091 (95% CI 0.0022, 0.55)] but not with rs9274619. CONCLUSIONS: Females and males with MPO-ANCA-positive AAV differ in genetic predisposition to disease, suggesting at least partially distinct disease mechanisms between the sexes. Double ANCA-positive AAV cases are genetically similar to PR3-ANCA-positive cases, providing clues to the clinical follow-up and treatment of these patients.

Surgical strategy for inflammatory thoracic aortic aneurysms in the endovascular surgery era.

OBJECTIVE: Inflammatory thoracic aortic aneurysms (TAAs) are very rare aortic conditions. Resection and replacement of the inflammatory aorta is the first-line treatment, and thoracic endovascular aortic repair (TEVAR) has recently been reported as a less invasive alternative even for this aortic cohort. In the present study, we reviewed our experience with inflammatory TAAs and assessed the preoperative management, surgical procedures, and outcomes. METHODS: From 2006 to 2019, 21 surgeries were performed for inflammatory TAAs in 17 of 2583 patients (0.7%) who had undergone cardiovascular surgery at our institution. The etiologies were Takayasu's arteritis in 13 patients, giant cell arteritis in 2, antineutrophil cytoplasmic antibody-associated vasculitis in 1, and unknown in 1. The mean follow-up period was 66.2 ± 50.2 months (range, 19-186 months). RESULTS: Three patients had undergone multiple surgeries. The aorta was replaced in 14 patients (ascending aorta in 9, aortic arch in 4, and thoracoabdominal aorta in 1). Three isolated TEVARs were performed in two patients and single-stage hybrid aortic repair (ascending aorta and partial arch replacement combined with zone 0 TEVAR) in four patients for extended arch and descending thoracic aortic aneurysms. Stent grafts were deployed on the native aorta in five of the seven TEVARs. The perioperative inflammation was well-controlled with prednisolone (mean dose, 7.4 ± 9.4 mg) in all patients except for one who had required two surgeries under inflammation-uncontrolled situations. No aorta-related complications, including anastomotic aneurysms and TEVAR-related aortic dissection, developed during the follow-up period, and the 5-year freedom from all-cause death was 92.9%. CONCLUSIONS: The mid-term outcomes of surgery for inflammatory TAAs were acceptable. Although replacement remains the standard procedure for inflammatory TAAs, TEVAR is a less invasive acceptable alternative when the inflammation is properly managed.

Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Accompanied by IgG4-Tubulointerstitial Nephritis with Underlying Sjögren Syndrome: A Case Report and Review of Literature.

OBJECTIVE: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of autoimmune multisystemic diseases characterized by necrotizing inflammation of small vessels and the presence of circulating ANCA. The prevalence of overlap AAV with other autoimmune diseases was low. CASE REPORT: We report a case of a 54-year-old woman who presented with a 20-year-history of sicca symptoms, the presence of anti-Ro/SS-A, anti-La/SS-B antibodies, myeloperoxidase -ANCA (MPO-ANCA), significant increase of serum IgG4 level, microscopic hematuria, non-nephrotic proteinuria, and progressive renal dysfunction. A renal biopsy showed pauci-immune necrotizing glomerulonephritis with crescents with severe tubulointerstitial nephritis (TIN) which shows extensive infiltration of IgG4-positive plasma cells. Considering these findings and the clinical course, the disease was considered more likely to be MPO-ANCA-associated vasculitis accompanied by IgG4-TIN with underlying primary Sjögren syndrome (pSS). CONCLUSION: This report shows a possible unusual disease overlap of MPO-ANCA-associated vasculitis and IgG4-TIN with underlying pSS.

Immunoadsorption Improves Remission Rates of Patients with Antineutrophil Cytoplasmic Antibody-Associated Vasculitis and Severe Kidney Involvement.

INTRODUCTION: The role of plasma exchange in treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) with severe kidney involvement is controversial. It is urgent to find effective treatments to improve prognosis of AAV patients. In this retrospective study, the outcomes of immunoadsorption (IA) onto protein A in AAV patients with severe kidney involvement were evaluated. METHODS: Clinical data of 60 patients with AAV and severe kidney involvement were analyzed. Patients received cyclophosphamide or rituximab for remission induction, among which 16 were additionally treated with IA. Remission, end-stage kidney disease (ESKD), death, and relapse were compared. RESULTS: Of 60 patients, 56 patients (93.3%) were positive for myeloperoxidase (MPO)-ANCA. At diagnosis, the estimated glomerular filtration rate and Birmingham Vasculitis Activity Score (BVAS) was 13.0 (7.7, 18.7) mL/min/1.73 m2 and 11.1 ± 3.4, respectively. After 3-17 days (mean 10.4 days) of induction treatment, the disease activity decreased more obviously in the IA group (p = 0.022) than the control group. IA showed superior over standard regimen in clearance of MPO-ANCA within 3-31 days (median 11 days) after treatment (78.4% vs. 9.3%, p = 0.005). After a median follow-up of 20.2 months, remission was achieved more quickly (p = 0.035) and higher (hazard ratio (HR) = 2.3, 95% confidence interval (CI): 1.1∼7.2, p = 0.033) in the IA group than the control group. IA therapy showed an advantage in reducing death (HR = 0.2, 95% CI: 0.1∼0.9, p = 0.032). There was no difference in developing into ESKD in both groups (HR = 0.7, 95% CI: 0.3∼2.0, p = 0.504). Multivariate Cox regression analysis indicated that early-stage remission was an independent predictor for ESKD (HR = 0.03, 95% CI: 0.003∼0.25, p = 0.001) and death (HR = 0.07, 95% CI: 0.01∼0.51, p = 0.009). CONCLUSION: IA treatment induces quicker and higher remission and lower mortality in AAV patients with severe kidney involvement. The early remission independently predicts the outcomes for these patients.