Search Results (114)

Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) is a heterogeneous group of small-vessel vasculitides, characterized by the presence of antibodies binding to myeloperoxidase (MPO) and proteinase-3 (PR3) found in neutrophil granules. Apart from being the target of ANCA, neutrophils actively contribute to the vicious cycle of inflammation and vascular damage in AAV. On the other hand, platelets have recently been recognized as essential for thrombosis and as inflammatory effectors that collaborate with neutrophils, reinforcing the generation of reactive oxygen species (ROS) and the formation of neutrophil extracellular traps (NETs) in those diseases. Neutrophils exhibit morphological and functional heterogeneity in AAV, reflecting the complexity of their contribution to disease pathogenesis. Since long-term immunosuppression may be related to serious infections and malignancies, there is an urgent need for reliable biomarkers of disease activity to optimize the management of AAV. This review summarizes the current understanding of the role of neutrophils and platelets in the pathogenesis of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), focusing on their crosstalk, and highlights the potential for identifying novel biomarkers relevant for predicting the disease course and its relapses. Full article

Background and objective. Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) affects small- to medium-sized vessels and is characterized by the production of ANCAs. The ANCA-negative term is used if the patient otherwise fulfills the definition for AAV but has negative results on serologic testing for ANCAs. The objective of this study was to compare ANCA-positive and -negative vasculitis patients and to evaluate the main differences possibly related to the presence of ANCAs. Material and methods. A cross-sectional study of 73 patients treated at the tertiary Rheumatology Centre of University Hospital from the 1 January, 2001, to the 31August, 2023, with diagnoses of AAV was carried out. Clinical characteristics and laboratory data were collected at the onset or at the first year of the disease. Results. Forty-eight (65.8%) patients were ANCA-positive, while twenty-five (34.3%) were ANCA-negative. Distribution by gender was similar in both groups, with a female–male ratio of 2:1. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were elevated for all AAV patients, but values were higher in the ANCA-positive patients’ group. The median hemoglobin was 106 g/L in the seropositive group and 127 g/L in the seronegative group. A higher prevalence of kidney involvement (60.4%) with elevated serum creatinine level (93.5 µmol/L) was observed in the ANCA-positive group compared with 24% and 70 µmol/l in the ANCA-negative group (p < 0.05). Neurological involvement was more frequently found in the ANCA-positive patient group, too: 29.2% compared to 20%. Among patients with ANCA-negative vasculitis, 88% had pulmonary; 92% ear, nose, throat (ENT); 48% joint; and 28% skin presentation. In comparison, involvement of these organs was less common in the ANCA-positive patients’ group, at 79.2%, 60.4%, 31.3%, and 25 %, respectively. Conclusions. ANCA-positive patients appear to be in a more difficult clinical situation in terms of organ involvement and laboratory changes. Full article

Background: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA), represent a spectrum of systemic disorders characterized by necrotizing inflammation of small- to medium-sized vessels. Nailfold videocapillaroscopy (NVC) is a validated, non-invasive technique routinely employed in the assessment of microvascular involvement in systemic sclerosis and in the differential diagnosis of Raynaud’s phenomenon; its application in the context of AAV, particularly EGPA, has not been investigated yet. The present study aims to assess the presence and the possible pattern of microcirculatory abnormalities detected by NVC in EGPA patients, and to explore potential correlations between capillaroscopic findings and disease activity status. Methods: A total of 29 patients with EGPA (19 women and 10 men), aged between 51 and 73 years, and 29 age- and sex-matched healthy controls were retrospectively enrolled between October 2023 and April 2025, after providing informed consent and meeting the inclusion and exclusion criteria. NVC was conducted in both groups to assess various morphological parameters, and mean capillary density was also calculated. Results: This study observed the presence of capillaroscopic alterations in the EGPA group, including decreased capillary density (38%), neoangiogenesis (72%), rolling (100%), pericapillary stippling (66%), and inverted capillary apex (52%). Overall, when comparing healthy controls with EGPA patients, microcirculatory abnormalities were significantly more prevalent in the latter. Specifically, scores for neoangiogenesis, capillary rolling, pericapillary stippling, and inverted capillary apex showed p-values < 0.001. Conclusions: Our study demonstrates a higher prevalence of four nailfold videocapillaroscopic abnormalities in patients with EGPA compared to healthy controls. However, the identification of these capillaroscopic alterations as specific to EGPA requires further confirmation. Ongoing studies aim to explore the potential role of NVC as a diagnostic marker and to investigate its correlation with the clinical manifestations of EGPA. Full article

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and interstitial lung disease (ILD) represent a complex interplay between autoimmune and fibrotic processes that poses significant diagnostic and therapeutic challenges. The distinction between isolated ANCA-ILD and AAV-ILD remains a subject of ongoing debate, with some researchers proposing that ANCA-ILD may be an early or restricted form of systemic vasculitis. Immunosuppressive therapy is the cornerstone of treatment for both diseases. However, there is increasing evidence that supports the potential role of antifibrotic agents in the management of progressive fibrosis. Management of these diseases requires a personalized approach that incorporates evaluation of biomarkers, imaging findings, and clinical risk factors to guide treatment decisions. Although current therapeutic strategies primarily target systemic inflammation, addressing the fibrotic components of these diseases is crucial for improving outcomes. Furthermore, emerging therapeutic options, such as B-cell depletion and antifibrotic therapies, offer promising outcomes. However, their roles in the treatment of AAV-ILD require further exploration. In this review, we discuss clinical insights and evolving therapeutic strategies for managing AAV and ANCA-positive ILD. In addition, we highlight the importance of early diagnosis and individualized treatment plans in improving the prognosis and quality of life of affected patients. Full article

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) constitutes a group of rare diseases characterized by autoimmune-associated inflammation and vessel damage. Based on the clinical manifestations and involvement of immune components, three disease syndromes are distinguished: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). In this review, we present the current data on the epidemiology, the clinical manifestations of each syndrome, and the most up-to-date classification criteria. The role of the underlying genetic and epigenetic abnormalities, as well as their interplay, is described. The immunological diversification of AAV is also described, with a focus on the immune cell dysfunctions detected in patients. In conclusion, we emphasize the urgent need to unravel the sophisticated mechanisms of this disease, which would enable the development of new, effective therapeutic strategies. Full article

Background and Objectives: This study investigated the frequency and clinical significance of subclinical but substantial peripheral arterial disease (PAD), identified using PAD evaluation, including pulse volume recording/ankle–brachial index (PVR/ABI), transcutaneous oxygen pressure (TcpO2), and skin perfusion pressure (SPP) tests in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Materials and Methods: This study included 54 patients with PAD evaluation results at or after AAV diagnosis. PVR/ABI and/or TcpO2 and/or SPP were performed on the same day. Abnormal PVR/ABI, TcpO2, and SPP were defined as PVR/ABI < 0.97, TcpO2 < 40 mmHg, and SPP < 50 mmHg, respectively. Poor outcomes included all-cause mortality, end-stage kidney disease (ESKD), cerebrovascular accidents, and acute coronary syndrome after PAD evaluation. Results: The median age of the 54 patients was 67 years, and 48.1% were male. In total, 3 of 54 patients (5.6%), 6 of 16 (37.5%), and 6 of 23 (26.1%) had abnormal PVR/ABI, TcpO2, and SPP, respectively. The concordance rate between abnormal PVR/ABI and abnormal TcpO2 or SPP was very low. Among the 54 patients, 5 (9.3%) died, and 2 (3.7%) progressed to ESKD. Abnormal SPP was significantly associated with cutaneous and renal manifestations at the time of PAD evaluation and had the potential to predict progression to ESKD during follow-up in patients with AAV. Conclusions: This study is the first to reveal the clinical usefulness of PAD evaluation: abnormal SPP may have the potential to identify subclinical but substantial PAD and can predict simultaneous kidney involvement as well as future progression to ESKD in patients with AAV. Full article

Background/Objectives: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a rare autoimmune disease marked by small-vessel inflammation. Pulmonary and renal manifestations are believed to critically influence prognosis, but detailed regional data are lacking. This study aimed to determine the prevalence and prognostic impact of pulmonary and renal involvement in AAV patients in the Thrace region of Türkiye. Methods: A retrospective cohort study was conducted on 78 biopsy-proven AAV patients followed between 2018 and 2025. Demographic, clinical, laboratory, and outcome data were analysed. Logistic regression identified predictors of relapse and mortality. Results: The cohort included 44 granulomatosis with polyangiitis, 30 microscopic polyangiitis, and 4 eosinophilic granulomatosis with polyangiitis patients; 40 were pr3-ANCA positive and 33 MPO-ANCA positive. Pulmonary involvement was observed in 71.8% and renal involvement in 74.4%, and overall mortality was 20.5%. All deaths occurred in patients with pulmonary involvement (28.6% vs. 0%, p = 0.048). Relapse was higher in those with pulmonary (17.9% vs. 4.5%, p = 0.048) and renal (15.5% vs. 5%, p = 0.056) involvement. Multivariate analysis showed that pulmonary involvement (OR 3.82, p = 0.002), renal involvement (OR 4.73, p = 0.013), and rituximab treatment (OR 10.79, p = 0.049) predicted relapse; elevated CRP (OR 1.01, p = 0.003), creatinine (OR 1.42, p = 0.028), hypoalbuminaemia (OR 0.24, p = 0.046), renal (OR 2.86, p = 0.031), and pulmonary (OR 3.21, p = 0.003) involvement predicted mortality. Conclusions: Pulmonary and renal involvement are highly prevalent and represent the strongest predictors of relapse and mortality in AAV patients in this regional cohort. Recognising these risks is essential to guide early interventions and improve patient outcomes. Full article

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of rare but potentially life-threatening autoimmune diseases that affect small to medium-sized blood vessels. Recent evidence highlights the critical role of neutrophil extracellular traps (NETs) in the pathophysiology of AAV. NETs, which are web-like structures composed of DNA and antimicrobial proteins, contribute to vascular damage and immune activation. In patients with AAV, excessive or impaired clearance of NETs can trigger autoantibody production and exacerbate inflammation. This literature review demonstrates the association between NETs and disease activity in AAV. Biomarkers such as MPO-DNA complexes and circulating free DNA can be used to assess disease activity and the response to treatment. Understanding NETosis in the clinical context could improve risk stratification, guide treatment decisions, enable the development of new targeted therapies, and support the development of more precise monitoring tools for AAV treatment. Full article

Objectives: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) comprises rare systemic vasculitides that can present with cognitive dysfunction. However, data on the screening and characterization of cognitive dysfunction in AAV remain limited. Methods: Cognitive complaints in AAV patients were screened using self-report questionnaires. Objective cognitive impairment was assessed with a standardized neurocognitive test battery. Results were compared with clinical evaluations, brain MRI findings, treatment history, and neuropsychiatric symptoms. All test results were standardized for the overall population. Results: Twelve patients (five women, seven men) with a median [IQR] age of 68 [59–71] and a median [IQR] disease duration of 92 months [55–127] were included. None of the patients showed evidence of vasculitis activity on brain MRI. Cognition was assessed using a standardized neurocognitive test battery in all patients except one. Four patients (36%) were found to have cognitive impairment, defined as three or more altered tests. The most affected functions were attentional and executive, with the d2-R (4/4), Rey–Osterrieth Complex Figure Delayed Recall (3/4), and Trail Making Test Part B (3/4) showing the most frequent deficiencies. Objective cognitive disorders were not associated with self-reported cognitive complaints. No significant association was found between cognitive impairment and vasculitis activity or sequelae, corticosteroid and immunosuppressive treatments, or neuropsychiatric symptoms. Conclusions: This study highlights the presence of cognitive impairments in AAV, predominantly affecting attentional and executive functions, which may reflect vascular involvement. Early and tailored approaches to cognitive screening and management are essential to improve patient care and quality of life. Full article

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (ANCA-vasculitis) is an autoimmune disease characterized by inflammation and necrosis of small or medium vessels. In the past, the role of the complement in the pathogenesis of ANCA-vasculitis has been underestimated, due to the paucity of the complement at sites of injured glomeruli. Following evidence from animal models of the major role of the complement in pathogenesis of ANCA-vasculitis, the complement has again attracted interest. Immunohistology analysis of pauci-immune glomerulonephritis—ANCA glomerulonephritis (ANCA-GN)—reveals the presence of complement products and membrane attack complex, suggesting their involvement in the disease process. Researchers emphasize the complement classical or lectin pathway as a contributor to the development of ANCA-vasculitis. The era of targeted therapies to suspend the complement activation as a therapy for ANCA-vasculitis has arrived, and thus, the comprehension of its role is very important. This review summarizes recent insights on the important role of complement activation in the development of ANCA-vasculitis as well as the emerging therapeutic possibilities that target complement components for the treatment of this condition. Full article

Background/Objectives: The overlap syndrome of primary Sjögren syndrome (pSS) with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) (OvSD/pSS/AAV) has been reported in other studies. This study applied the new criteria for AAV proposed by the American College of Rheumatology/European Alliance of Associations for Rheumatology in 2022 (the ACR/EULAR criteria) to patients with pSS presenting signs and symptoms suggestive of small- and medium-vessel vasculitis. It also investigated the overall frequency of OvSD/pSS/AAV and the major contributing factors to its reclassification. Methods: This study included 116 patients with pSS from March 2005 to December 2020, according to the inclusion criteria, and defined signs and symptoms suggestive of small- or medium-vessel vasculitides as lung parenchymal lesions supporting AAV, peripheral neuropathy, and suspected renal vasculitis. The classification could be made when the total scores for microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) are ≥5 points and the eosinophilic GPA (EGPA) score is ≥6 points. Results: The median age of the patients was 56.0 years, and 101 patients (87.1%) were women. In total, 95, 12, and 37 patients had lung parenchymal lesions supporting AAV, peripheral neuropathy, and suspected renal vasculitis, respectively. According to the ACR/EULAR criteria for AAV, 35 of 116 (30.2%) patients were reclassified as having OvSD/pSS/AAV. Among these 35 patients, 4 were reclassified as having both OvSD/pSS/MPA and OvSD/pSS/GPA and 1 as having both OvSD/pSS/MPA and OvSD/pSS/EGPA simultaneously. The major contributing factor to the reclassification of OvSD/pSS/AAV was ANCA positivity. Conclusions: The overall frequency of the reclassification of OvSD/pSS/AAV was 30.2% in pSS patients presenting signs and symptoms suggestive of small- and medium-vessel vasculitis. Its likelihood increased according to ANCA positivity. Full article

Objectives: This study investigated whether serum soluble CD200 (sCD200) and soluble receptor for CD200 (sCD200R) concentrations and serum sCD200/sCD200R ratios at diagnosis could predict cross-sectional activity in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Methods: We included 70 patients with AAV in this pilot study, retrospectively reviewed their medical records, and collected clinical data at the time of AAV diagnosis. We also measured sCD200 and sCD200R in stored blood samples collected at diagnosis. In medical records, AAV activity at diagnosis had been assessed according to the Birmingham Vasculitis Activity Score (BVAS). The prediction potential of serum sCD200 and sCD200R concentrations and serum sCD200/sCD200R ratios for BVAS was evaluated using Pearson correlation analysis. Results: Among the 70 patients, the median age was 63.5 years, with 29 males and 41 females. Among the three CD200-related variables at diagnosis, serum sCD200/sCD200R ratios at diagnosis were significantly correlated with cross-sectional BVAS; however, serum sCD200 and sCD200R concentrations were not correlated with it. These results may indicate that serum sCD200/sCD200R ratios may better help predict cross-sectional AAV activity by increasing the range of opposing changes in the two variables. On the other hand, both serum sCD200 concentrations and serum sCD200/sCD200R ratios showed significant correlations with cross-sectional myeloperoxidase-ANCA titre, five-factor score, and serum creatinine levels at diagnosis. Conclusions: In this study, we demonstrated that serum sCD200/sCD200R ratios at diagnosis can be a useful and convenient biomarker to predict cross-sectional AAV activity calculated according to BVAS. Full article

Background/Objectives: Previous studies have revealed the predictive potential of remnant cholesterol (RC) for acute coronary syndrome (ACS) occurrence in the general population. However, whether this association applies to patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV), in which a lipid paradox exists, remains unclear. We investigated whether RC levels at diagnosis could predict ACS occurrence during follow-up in patients with AAV. Methods: This study included 139 patients with AAV. ACS was defined as ST-elevation myocardial infarction (STEMI), non-STEMI, or unstable angina occurring after AAV diagnosis. RC levels were calculated as (total cholesterol)–(low-density lipoprotein cholesterol)–(high-density lipoprotein cholesterol). Patients were categorised into three groups by RC tertiles: highest (≥26.2 mg/dL), middle (19.1−26.1 mg/dL), and lowest (≤19.0 mg/dL) tertile groups. Results: The median age of the 139 patients (male, 31.7%) was 58.0 years. During follow-up, six, two, and one patients were diagnosed with ACS in the highest, middle, and lowest tertile groups, respectively. Patients in the highest tertile group exhibited a significantly lower ACS-free survival rate than those in the lowest tertile (p = 0.030). In the multivariable Cox hazards model, male sex (hazard ratio [HR] 9.054, 95% confidence interval [CI] 1.786−45.910), Birmingham vasculitis activity score (HR 1.147, 95% CI 1.033−1.274), and the highest tertile of RC levels (HR 10.818, 95% CI 1.867–62.689) were significantly and independently associated with ACS occurrence during follow-up in patients with AAV. Conclusions: Our findings indicate that RC levels at diagnosis may predict ACS occurrence during follow-up in patients with AAV, regardless of the traditional cardiovascular risk factors. Full article

The complement cascade and Neutrophil Extracellular Traps (NETs) represent fundamental tools in protecting the host from foreign pathogens. Complement components and relative fragments, classically assigned to the innate immunity, represent a key link with the humoral immune response. NETs are a crucial component of the innate immune response, consisting of chromatin release from activated neutrophils. These web-like structures facilitate pathogen entrapment and elimination through proteolytic degradation and antimicrobial effectors. Previous findings suggested complement components and NETs have a significant role in the pathogenesis of several diseases characterized by inflammation, such as autoimmune and infectious diseases. However, the crosstalk between NETs and the complement cascade has only recently been investigated, and several aspects still need to be fully clarified. Recent evidence seems to suggest a bidirectional link between the complement cascade and NETosis. We here present the interaction between complement components and NETs in specific autoimmune diseases that mostly affect the kidney, such as systemic lupus erythematosus, Antineutrophilic Cytoplasmic Antibody (ANCA)-associated vasculitis and antiphospholipid syndrome. The mechanisms reported here may represent specific targets for the development of possible therapeutic strategies. Full article

Background: Microscopic polyangiitis (MPA) is a type of necrotizing vasculitis that primarily affects small vessels and belongs to the spectrum of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs). While previous studies have identified potential prognostic biomarkers, further research is needed to validate a reliable marker for risk stratification in clinical practice. Kidney injury molecule-1 (Kim-1), a transmembrane protein expressed on proximal tubular epithelial cells, has been implicated in tubular damage. This study investigated the potential of Kim-1 as a biomarker in MPA. Methods: Kidney biopsy tissues, along with urine and blood samples, were retrospectively analyzed from 52 MPA patients and compared to urine samples from 7 healthy controls. Global disease activity was assessed using the Birmingham vasculitis activity score (BVAS) and vasculitis damage index, while renal disease activity was evaluated using renal BVAS (BVAS-R). Results: Urinary Kim-1 levels were significantly elevated in MPA patients compared to healthy controls. Urinary Kim-1 was positively correlated with the Mayo Clinic Chronicity Score (MCCS) but not with the ANCA Kidney Risk Score (AKRiS), whereas tubular Kim-1 was associated with AKRiS but not with MCCS, indicating their distinct pathological significance. Higher tubular Kim-1 expression was observed in patients with elevated BVAS-R. Urinary Kim-1 levels correlated with proteinuria and were associated with the Mayo Clinic Chronicity Score (MCCS) and ANCA Kidney Risk Score (AKRiS) but not with glomerular lesion severity. Unlike C-reactive protein (CRP), neither urinary nor tubular Kim-1 predicted MPA recurrence. Conclusions: Urinary Kim-1 reflects histopathologic findings and renal impairment but does not predict systemic disease activity or recurrence in MPA, demonstrating its potential clinical utility as a biomarker for assessing chronic renal damage. Full article