Search Results (172)

Background: The complement system factors’ role in the pathogenesis of autoimmunological diseases is known, but the influence of autoantibodies against complement factors’ receptors on the course of specific glomerular diseases remains unclear. Methods: We measured the levels of anti-C3aR and anti-C5aR antibodies in patients with membranous nephropathy (n = 18), primary focal and segmental glomerulosclerosis (FSGS) (n = 25), lupus nephritis (LN) (n = 17), IgA nephropathy (n = 14), mesangial proliferative (non-IgA) glomerulonephritis (n = 6), c-ANCA (cytoplasmic anti-neutrophil cytoplasmic antibodies) vasculitis (n = 40), and p (perinuclear)-ANCA vasculitis (n = 16). These conditions were compared to a healthy control group (n = 22). Then, for up to two years, we tracked the patients’ clinical progress (in terms of creatinine, total protein, and albumin levels) and compared the outcomes with their antibody levels. Results: The lupus nephritis group had higher levels of anti-C3aR and anti-C5aR antibodies than the other groups. The lupus nephritis group’s anti-C3aR antibody level showed a negative correlation with albumin and total protein at several time points of observation. Additionally, at numerous observational points, the anti-C3aR antibody level showed a positive correlation with both the basic albumin level in the FSGS group and the total protein level. Conclusions: The anti-C3aR and anti-C5aR antibodies are higher in lupus nephritis patients compared to other glomerulonephritis patients and healthy individuals. Albumin and total protein levels appear to be correlated positively with anti-C3aR antibody levels in FSGS and negatively in lupus nephritis. Full article

Central nervous system (CNS) involvement is an extremely rare manifestation in eosinophilic granulomatosis with polyangiitis (EGPA), associated with a poor prognosis. Here we present a case of 50-year-old female patient with long-term asthma treatment who presented initially with extreme eosinophilia (56%) and severe progressive ascending paresis, similar to Guillain–Barré syndrome, leading to tetraplegia. After navigating through diagnostic mazes, the diagnosis of EGPA was established based on eosinophilia, myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) positivity, asthma, eosinophil granulomatosis in the gastrointestinal tract, and severe peripheral nervous system involvement, complicated with rare central nervous granulomas and ischemia. With combined immunosuppressive and immunomodulatory treatment including high-dose corticosteroids, rituximab and intravenous immunoglobulin along with symptomatic treatment and planned rehabilitation over 6 months, our patient recovered gradually from tetraplegia and adverse events such as severe infections and osteoporotic fractures. Now, from a 2-year perspective, we can conclude a successful treatment leading to decrease in all of her symptoms. Due to persistent eosinophilia after steroid tapering, she was switched to mepolizumab maintenance treatment and demonstrated continuous improvement of motor and sensory functions. Thanks to periodically repeated rehabilitation, she became self-sufficient and returned to her previous job. Our case highlights that EGPA patients should be treated in a center of expertise due to the rarity of the disease and complexity of diagnosis and treatment. Careful multidisciplinary cooperation, the huge effort of the patient, and a supportive environment can show a way back from immune-mediated tetraplegia. Full article

Eosinophilic Granulomatosis with Polyangiitis (EGPA) is a rare systemic vasculitis with eosinophilic inflammation and variable clinical presentations. Although skin manifestations are frequent, current classification criteria do not include them, which may underestimate their diagnostic value. This prospective observational study aimed to assess systemic and skin involvement as well as eosinophilia, anti-neutrophil cytoplasmic antibody (ANCA), and Anti-nuclear antibodies (ANA) serum levels in 20 EGPA patients followed for one year at the University Hospital of Messina, Italy, before starting Mepolizumab, 300 mg. Eosinophilia, ANCA status, systemic and skin involvement were also evaluated at 6 and 12 months; a literature review on these data supplements our findings. Skin involvement was present in 55% of patients, including purpura, urticarial vasculitis, angioedema, maculopapular rash, and nodules, mostly in ANCA-negative patients, though purpura was more frequent in ANCA-positive cases but without any statistically significant correlation. ANAs were present in 50% of patients, together with ANCA in two subjects and without in eight. Mepolizumab significantly reduced eosinophil levels, BVASs, and corticosteroid dependence, with notable improvement in skin symptoms. In conclusion, skin manifestations are common in EGPA and may represent useful indicators of disease activity. Their integration with ANCA status, eosinophil counts, and positivity to other autoantibodies could enhance diagnostic and monitoring strategies identifying different clusters of EGPA patients even if the small sample size limits the generalizability of the findings. Full article

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

Objectives: Previous studies have suggested differences in vasculitic and eosinophilic phenotypes based on anti-neutrophil cytoplasmic antibody (ANCA) positivity in eosinophilic granulomatosis with polyangiitis (EGPA). However, their relevance under the 2022 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) classification criteria remains unclear. We aimed to evaluate the clinical features and outcomes of EGPA according to myeloperoxidase (MPO)-ANCA status in a Korean cohort. Methods: We conducted a retrospective cohort study that included 57 patients with EGPA without proteinase 3-ANCA positivity who fulfilled the 2022 ACR/EULAR classification criteria. Patients were classified into MPO-ANCA-positive (n = 25) and MPO-ANCA-negative (n = 32) groups. Clinical manifestations, laboratory findings, and outcomes, including all-cause mortality, relapse, end-stage kidney disease (ESKD), cerebrovascular accident (CVA), and acute coronary syndrome (ACS), were compared between the two groups. Results: MPO-ANCA-positive patients exhibited higher Five-Factor Scores (1.0 [0.0–1.0] vs. 0.0 [0.0–1.0], p = 0.038), lower Short Form 36 Physical Component Summary scores (35.0 [19.7–56.3] vs. 52.5 [43.5–69.7], p = 0.048), and elevated systemic inflammation markers (higher erythrocyte sedimentation rate: 58.0 [16.0–97.5] mm/hr vs. 25.5 [7.0–63.8] mm/hr, p = 0.026). Constitutional symptoms were more frequent among MPO-ANCA-positive patients (n = 14 [56.0%] vs. n = 3 [9.4%], p < 0.001), whereas no significant differences were found in vasculitic or eosinophilic manifestations. Kaplan–Meier analysis revealed no differences in the overall (p = 0.36), relapse-free (p = 0.80), ESKD-free (p = 0.87), CVA-free (p = 0.26), or ACS-free (p = 0.94) survival rates between the two groups. Conclusions: In Korean patients with EGPA classified under the 2022 ACR/EULAR classification criteria, MPO-ANCA positivity, as compared to ANCA-negative status, was associated with a higher disease burden and poorer quality of life but not with distinct vasculitic or eosinophilic manifestations and adverse outcomes. 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: Anti-PAR 1 (protease-activated receptor 1) and anti-ACE 2 (angiotensin 2-converting enzyme 2) antibodies are a kind of non-HLA (human leukocyte antigens) antibodies postulated to be of significance in autoimmunological diseases and organ transplantation. Methods: We assessed anti-PAR 1 and anti-ACE 2 antibody levels in patients with membranous nephropathy n= 18, focal and segmental glomerulosclerosis (FSGS) n = 25, lupus nephritis (LN) n = 17, IgA nephropathy n = 14, mesangial proliferative (non-IgA) glomerulonephritis n = 6, c-ANCA (cytoplasmic anti-neutrophil cytoplasmic antibodies) vasculitis n = 40, p (perinuclear)-ANCA vasculitis n = 16, and compared them with a healthy control group n = 22. Next, we observed the clinical course of the patients (creatinine, total protein, and albumin) up to 2 years and correlated the results with the level of antibodies. Results: The anti-PAR 1 antibody level was lower in membranous nephropathy and FSGS compared to the control group. Anti-PAR 1 antibody levels were higher in secondary compared to primary glomerulonephritis. Both anti-PAR 1 and anti-ACE 2 antibody levels correlated positively (in focal and segmental glomerulosclerosis) or negatively (in lupus nephritis) with total protein and albumin at different time points of observation. Anti-PAR 1 and anti-ACE 2 antibody levels correlated also with creatinine level at one time point of observation in IgA nephropathy. Anti-PAR 1 and anti-ACE 2 antibodies correlated with each other in membranous nephropathy, FSGS, and p- and c-ANCA vasculitis (p < 0.05). Conclusions: The anti-PAR 1 antibody level was lower in membranous nephropathy and focal and segmental glomerulosclerosis compared to the control group. Anti-PAR 1 antibody levels tend to be higher in secondary compared to primary glomerulonephritis. Full article