Search

Granulomatosis with polyangiitis (GPA) is a severe autoimmune vasculitis associated with the presence of anti-neutrophil cytoplasmic antibodies (ANCA) mainly targeting proteinase 3 (PR3), a neutrophilic serine proteinase. PR3-ANCA binding to membrane-bound PR3 on neutrophils induce their auto-immune activation responsible for vascular lesions. However, the correlation between PR3-ANCA level and disease activity remains inconsistent, suggesting the existence of non-pathogenic PR3-ANCA. In order to prove their existence, we immortalized B lymphocytes from blood samples of GPA patients in remission having persistent PR3-ANCA to isolate non-activating PR3-ANCA. We obtained for the first time a non-activating human IgG1κ anti-PR3 monoclonal antibody (mAb) named 4C3. This new mAb binds soluble PR3 with a high affinity and membrane-bound PR3 on an epitope close to the PR3 hydrophobic patch and in the vicinity of the active site. 4C3 is able to bind FcγRIIA and FcγRIIIB and has a G2F glycosylation profile on asparagine 297. 4C3 did not induce activation of neutrophils and could inhibit human polyclonal PR3-ANCA-induced activation suggesting that 4C3 is non-pathogenic. This characteristic relies on the recognized epitope on PR3 rather than to the Fc portion properties. The existence of non-pathogenic PR3-ANCA, which do not activate neutrophils, could explain the persistence of high PR3-ANCA levels in some GPA patients in remission and why PR3-ANCA would not predict relapse. Finally, these results offer promising perspectives particularly regarding the understanding of PR3-ANCA pathogenicity and the development of new diagnostic and therapeutic strategies in GPA.

The article presents up-to-date data on etiopathogenesis, clinic, diagnostics, differential diagnostics, treatment and prognosis in granulomatosis with polyangiitis (GPA). Early diagnosis of GPA is a difficult clinical task and requires careful examination of the patient using modern research methods to identify pathognomic symptoms. Early detection of anti-neutrophil cytoplasmic antibodies (ANCA) increases the frequency of GPA diagnosis, a biopsy of affected organs allows verifying the diagnosis morphologically. Only timely establishment of the diagnosis allows prescribing therapy as early as possible and avoiding disability of patients. [ABSTRACT FROM AUTHOR]

Objective: To provide a comprehensive review of the central nervous system (CNS) involvement in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), including the pathogenesis, clinical manifestations, ancillary investigations, differential diagnosis, and treatment. Particular emphasis is placed on the clinical spectrum and diagnostic testing of AAV.Recent Findings: AAV is a pauci-immune small-vessel vasculitis characterized by neutrophil-mediated vasculitis and granulomatousis. Hypertrophic pachymeninges is the most frequent CNS presentation. Cerebrovascular events, hypophysitis, posterior reversible encephalopathy syndrome (PRES) or isolated mass lesions may occur as well. Spinal cord is rarely involved. In addition, ear, nose and throat (ENT), kidney and lung involvement often accompany or precede the CNS manifestations. Positive ANCA testing is highly suggestive of the diagnosis, with each ANCA serotype representing different groups of AAV patients. Pathological evidence is the gold standard but not necessary. Once diagnosed, prompt initiation of induction therapy, including steroid and other immunosuppressants, can greatly mitigate the disease progression.Conclusions and Relevance: Early recognition of AAV as the underlying cause for various CNS disorders is important for neurologists. Ancillary investigations especially the ANCA testing can provide useful information for diagnosis. Future studies are needed to better delineate the clinical spectrum of CNS involvement in AAV and the utility of ANCA serotype to classify those patients.Evidence Review: We searched Pubmed for relevant case reports, case series, original research and reviews in English published between Sep 1st, 2001 and Sep 1st, 2018. The following search terms were used alone or in various combinations: “ANCA,” “proteinase 3/PR3-ANCA,” “myeloperoxidase/MPO-ANCA,” “ANCA-associated vasculitis,” “Wegener's granulomatosis,” “microscopic polyangiitis,” “Central nervous system,” “brain” and “spinal cord”. All articles identified were full-text papers.

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic vasculitis associated with asthma, anti-neutrophil cytoplasmic antibodies (ANCA) positivity, and tissue eosinophilia. Objective: To describe the presenting clinical features, significant biochemical alterations, and also potential pathogenic factors in adult patients diagnosed in our Center over a period of >20 years. Method: A retrospective study of EGPA patients diagnosed from 1994 to 2019 at ASST Grande Ospedale Metropolitano Niguarda Ca' Granda, Milan (Italy), which was performed according to the 1990 American College of Rheumatology criteria and Chapel Hill Consensus Conference definition. A dataset was compiled, registering demographic and clinical features, biochemical analysis at onset, and also the therapies received 3 months prior to EGPA diagnose. Statistical analyses were subsequently conducted dividing patients in 2 groups based on ANCA positivity and comparing them. Results: Two groups were clearly identified by ANCA serology and specific organ involvement in accordance with literature reports; however, our data underline for the first time the association between anti-leukotriene receptor antagonists (LTRAs) and ANCA positivity. The group of previously treated patients presents an OR of 6.42 to be ANCA positive. This finding could be attributed to an imbalanced stimulation of leukotriene receptors, inducing both mast cells activation and an increased neutrophil extracellular traps release from neutrophils. Conclusion: Despite the limitations of this retrospective study, the association between LTRAs and ANCA antibodies elucidates the mechanism by which innate immunity is directly involved in tolerance breakdown and autoantibodies production. Validation of our results with targeted studies could clarify the differences between ANCA-positive and ANCA-negative patients with important consequences on the use of some drug classes in the treatment of EGPA and asthmatic subjects. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) may play an important role in both inflammation with subsequent fibrosis and in repair and healing in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We evaluated the circulating levels of MMPs, including pregnancy-associated plasma protein A (PAPP-A), and TIMPs in patients with AAV. PAPP-A, MMP-2, MMP-3, MMP-7, MMP-9, TIMP-1, TIMP-2 and selected parameters were measured in 100 AAV patients (36 patients with active disease and 64 patients in remission) and 34 healthy subjects. The levels of MMP-2, MMP-3, MMP-7, MMP-9, TIMP-1, TIMP-2, and PAPP-A in AAV were all found to be different to those of the controls. The MMP-7 and PAPP-A concentrations were increased in active disease in comparison to the controls (MMP-7: 13 ±.7 vs. 2 ± 0.6 ng/ml, PAPP-A: 14 ± 18 vs. 6.8 ± 2.6 ng/ml, both P < 0.005). The MMP-2 and TIMP-2 levels were increased in remission when compared to the controls (MMP-2: 242 ± 50 ng/ml vs. 212 ± 26 ng /ml, TIMP-2: 82 ± 14 ng/ml vs. 68 ± 93 ng/ml) and to the active AAV (MMP-2: 242 ± 50 vs. 219 ± 54 ng/ml, TIMP-2: 82 ± 14 ng/ml vs. 73 ± 15 ng/ml, all P < 0.005). MMP-3, MMP-7, TIMP-1, and PAPP-A correlated with serum creatinine. The serum levels of MMPs, TIMPs and PAPP-A are all altered in AAV. MMP-2, MMP-7 and TIMP-2 appear to be promising markers in distinguishing active AAV from remission. MMP-3, MMP-7, TIMP-1, and PAPP-A are associated with kidney function in AAV. Further studies are needed to delineate the exact roles of circulating MMPs, TIMPs and PAPP-A in patients with AAV. [ABSTRACT FROM AUTHOR]

Purpose of Review: ANCA-associated vasculitides (AAV) are a group of rare diseases characterized by blood vessel inflammation and the presence of circulating anti-neutrophil cytoplasmic antibodies recognizing proteinase-3 (PR3) (PR3-ANCA) or myeloperoxidase (MPO), MPO-ANCA. Recent Findings: Historically, ANCAs have been used as biomarkers for disease associations and increases of ANCA levels as predictors of relapse in patients with AAV. Summary: In this review, we will summarize and highlight the most recent developments for using ANCA as predictive biomarkers and review some of the important disease-specific features in patients with AAV. [ABSTRACT FROM AUTHOR]

Aim: Anti‐neutrophil cytoplasmic antibodies (ANCA) have a role in the diagnostic workup of ANCA‐associated vasculitis. However, the clinical significance of positive ANCA in the absence of vasculitis is yet to be determined. Therefore, we sought to investigate the clinical spectrum and rate of patients with a positive ANCA without evidence of vasculitis. Methods: Retrospective analysis of patients positive for cytoplasmic ANCA (C‐ANCA) and proteinase 3 (PR3) or P‐ANCA and myeloperoxidase (MPO) between 2007 and 2016 in the Chaim Sheba Medical Center, Israel. The proportion of patients who had no evidence of vasculitis among all patients with a positive C‐ANCA/PR3 or P‐ANCA/MPO was calculated according to tertiles of enzyme‐linked immunosorbent assay (ELISA) antibody levels. Results: Among 113 patients who tested positive for C‐ANCA/PR3 or P‐ANCA/MPO, 68 (60.1%) had no evidence of vasculitis. ELISA antibody titers were significantly higher among patients with vasculitis than those without (6.2 vs 3.2, for C‐ANCA/PR3 and 5.4 vs 2.6 for P‐ANCA/MPO, P < 0.05). The proportion of patients without vasculitis among all patients with a positive C‐ANCA/PR3 and among all patients with a positive P‐ANCA/MPO declined in parallel to the increases in ELISA antibody level tertiles (96%, 57% and 22% in the 1st, 2nd and highest tertiles, respectively, for patients with C‐ANCA/PR3 patients and 100%, 66% and 20% in the 1st, 2nd and highest tertiles, respectively, for patients with P‐ANCA/MPO). Conclusion: A significant proportion of patients with a positive C‐ANCA/PR3 or P‐ANCA/MPO do not have evidence of vasculitis, particularly those with low‐medium ELISA antibody titers. Using a higher threshold of ANCA titers may be required to improve specificity. [ABSTRACT FROM AUTHOR]

Introduction Granulomatosis with Polyangiitis (GPA) is a small vessel vasculitis characterized by a necrositing granulomatous inflammation of the upper and lower respiratory tracts and focal/proliferative glomerulonephritis. In more than 70% of the cases, the presenting symptoms are head and neck manifestations that are often misdiagnosed as infectious or allergic in etiology. Objective The present study provides an analysis of head and neck manifestations in a series of patients diagnosed with GPA. It also evaluates their medical and surgical treatment and provides a review of the relevant literature. Methods A retrospective analysis of 19 patients diagnosed with GPA at a public tertiary care hospital between 2006 and 2017 was performed. Results A total of 19 patients were included in the present study, and 16 of them presented head and neck manifestations. Sinonasal symptoms were the most common, affecting 56% of the patients, followed by laryngotracheal (31.25%) and ear (25%) symptoms. In 7 patients, sinonasal symptoms were the first manifestation of the disease (43.75%). Four patients underwent surgery at some stage of the disease. Conclusions Head and neck involvement is common in GPA and may stand for the first or the only manifestation of the disease. The otolaryngologists play a central role in the diagnosis and long-term treatment of these patients, and they have to keep this pathology in mind when treating patients with ENT symptoms that do not respond as expected to the treatment. [ABSTRACT FROM AUTHOR]

We describe the case of a 61-year-old woman who presented with progressive respiratory symptoms and imaging demonstrating multiple opacities in the right lung with hilar and mediastinal lymphadenopathy suggestive of multifocal adenocarcinoma. Subsequent biopsies were consistent with focal changes of organising pneumonia (OP) and no evidence of malignancy. She was treated with steroids for cryptogenic OP with limited response. There was clinical and radiological progression with new lung nodules, mediastinal and thoracic spinal canal infiltration. There was ongoing concern that clinical findings represented disseminated malignancy. Following further investigation and multidisciplinary respiratory and rheumatology review, a diagnosis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) -- granulomatosis with polyangiitis (GPA) was confirmed. The case highlighted the multisystem nature of GPA with unusual dural and large vessel aortic and pulmonary trunk involvement. [ABSTRACT FROM AUTHOR]

Systemic vasculitides (SV) are a heterogeneous group of acute and chronic diseases, the most important pathomorphological sign of which is inflammation and necrosis of the vascular wall. The basis for the classification of SV is their etiology and pathogenesis, the type of affected vessels and the pattern of inflammation, predominant organ involvements, clinical manifestations, a genetic predisposition, and demographic characteristics. To diagnose vasculitis is a difficult task due to a broad spectrum of its clinical manifestations that depend on the predominant size of affected vessels, the involved organs and systems, and the magnitude of the inflammatory process. There are no specific laboratory tests for most forms of SV; nonspecific inflammatory measures and activated autoimmune reactions are noted to be higher. Screening for SV determines the levels of anti-neutrophil cytoplasmic antibodies (ANCA), cryoglobulins, anti-glomerular basement membrane antibodies, and anti-complement C1q antibodies. However, biopsy with its specimen being pathomorphologically characterized, as well as current noninvasive or minimally invasive diagnostic techniques remain relevant because of a large number of seronegative variants of vasculitis. The ANCA-associated vasculitis management algorithm developed by the British Society of Rheumatology has been presented in 2015. The timely diagnosis and treatment at the onset of SV is the basis for quality of life and survival improvement.

Introduction: Anti-glomerular basement membrane (anti-GBM) disease is a rare organ-specific autoimmune disease. The overall and renal outcomes of patients have mostly been reported in small-sized cohorts. We aimed to study the clinical profile, overall survival, and renal survival of anti-glomerular basement membrane disease patients at our center., Methods: We conducted a retrospective analysis of the data regarding the clinical profile and renal survival of patients diagnosed with anti-GBM disease from October 2019 to March 2022, having a minimum follow-up of 12 months., Results: There were 15 patients in the study, with the mean age of presentation being 51.6 ± 13.7 years. The median duration of symptoms onset to the nephrologist opinion was 15 (10-23) days. The extrarenal manifestations were seen in the respiratory, otorhinolaryngological, and neurological systems. The mean serum anti-GBM titers were 154.5 (14.9-263.5) U/mL. Serum anti-GBM titers were present in 13/15 (86.6%) patients, and 12/13 (92.3%) patients had above the reference range. Anti-neutrophil cytoplasm antibody (ANCA) levels were assessed in 12/15 (80%) patients, and 9/12 (75%) had higher levels. Renal biopsy was available in 14 patients with more than 50% crescents. Along with crescents, necrotizing lesions, rupture of the Bowman's capsule, and granulomatous lesions were also seen. Among the initial therapies, the steroid pulse was given to 13 (86.6%) patients, whereas membrane plasmapheresis was given to 8 (53.3%) patients. Inj. cyclophosphamide and inj. rituximab were given to 8 (53.3%) and 4 (26.6%) patients, respectively. No difference was seen in clinical characteristics, renal biopsy features, treatment received, and outcomes with ANCA positivity except for age, where patients who were ANCA positive were older compared to patients who were ANCA negative. One-year renal and patient survival was seen in 4 (26.6%) and 6 (40%) patients, respectively., Conclusion: Most patients of anti-GBM disease have active sediments, raised creatinine, and non-specific symptomatology. There is poor renal and patient outcome as most patients present with advanced renal failure., Competing Interests: The authors declare no conflict of interest related to this manuscript., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Our aim was to evaluate the pathogenic role of anti-neutrophil cytoplasmic antibodies (ANCAs) in patients with IgA nephropathy (IgAN). A total of 2390 patients with biopsy-confirmed IgAN were analyzed retrospectively. Thirty-five IgAN patients with ANCA and 40 IgAN patients without ANCA were enrolled. According to the Birmingham Vasculitis Activity Score (BVAS) items, the ANCA-positive patients were further divided into two subgroups which with or without systemic symptoms. The cumulative renal survival rate was calculated using Kaplan-Meier analysis. Comparisons between groups were made using the log rank test. Among the 35 ANCA-positive patients, 14 (40%) had systemic symptoms. Compared with ANCA-positive patients without systemic symptoms, ANCA-positive patients with systemic symptoms had a shorter duration of disease (1.0 [IQR, 0.3-6.8] vs. 6.0 [IQR, 2.0-21.0], P = 0.011); showed worse renal function with lower levels of eGFR (24.2 [IQR, 11.7-74.9] vs. 100.1 [IQR, 59.6-130.2] mL/min/1.73 m2, P = 0.002), serum albumin (30.4 [IQR, 27.4-34.8] vs. 41.5 [IQR, 35.1-44.4] g/L, P = 0.001), and hemoglobin (96.1 ± 21.5 vs. 118.2 ± 22.4 g/L, P = 0.006); and presented relatively higher incidences of rapidly deteriorating kidney function (28.6 vs. 0.0%, P = 0.039) and moderate-to-severe tubular atrophy (78.6 vs. 23.8%, P = 0.001). Kaplan-Meier analysis had shown that ANCA-positive patients with systemic symptoms had lower cumulative renal survival rate compared with both ANCA-positive patients without systemic symptoms and ANCA-negative patients (log rank = 14.40, P < 0.001). Evaluation of systemic symptoms is a simple, readily available clinical tool to predictive the pathogenic role of ANCA in IgAN. [ABSTRACT FROM AUTHOR]

Cystic fibrosis (CF) is an inflammatory lung disease. Platelets have an emerging role in inflammation, however previous studies of platelet activation in CF have generated conflicting results. In this study, we determined platelet function in CF patients and correlated platelet activation to establish clinical and laboratory parameters. Twenty-two patients, aged 20.7 to 54.4 (mean 34.0, SD 9.45) years and with a mean FEV1%pred (forced expiratory volume in one second, % of predicted) of 72 (SD 21.4, range 32–110) were recruited. A combination of platelet assays was used: platelet aggregation, platelet activation and platelet-leukocyte complex formation. Platelets from CF patients exhibited significantly increased aggregation when stimulated ex-vivo, a tendency towards increased platelet upregulation of CD62P, but no increase of GPIIb/IIIa activation (PAC-1). Platelet-monocyte complex (PMC) formation was significantly increased in CF patients compared to controls, while platelet-neutrophil complex formation was not. In the CF group, platelet aggregation correlates with levels of anti-neutrophil cytoplasmic antibodies (ANCA) with specificity for bactericidal/permeability-increasing protein (BPI), BPI-ANCA (r = 0.56). The formation of PMCs correlates with lung function decline (1-FEV1%), CRP and BPI-ANCA (r = 0.61, 0.55, 0.5). We therefore confirm the presence of increased platelet activation in CF patients, and determine that further evaluation of platelet activation in relation to prognostic factors in CF is warranted. [ABSTRACT FROM AUTHOR]

Autoimmune hepatitis (AIH) is a progressive, chronic liver disease characterized by unresolving hepatocellular inflammation of autoimmune origin. The clinical spectrum may vary from asymptomatic presentation, to non-specific symptoms such as fatigue, arthralgias, nausea and abdominal pain, to acute severe liver disease. AIH is characterized by the presence of interface hepatitis and portal plasma cell infiltration on histological examination, hypergammaglobulinemia, and positive autoantibodies. AIH is associated with other autoimmune diseases and its course is often accompanied by various non-specific hematological disorders. However, the coexistence of autoimmune neutropenia (AIN) is infrequent. We present a case of a female patient diagnosed with type 1 AIH and agranulocytosis on presentation. A diagnosis of AIN was established, based on the patient's sex, the underlying liver disease, the absence of alternative causes, the presence of atypical anti-neutrophil cytoplasmic antibodies in patient's serum and the favorable and dosedependent treatment of both pathologic entities with corticosteroids and mycophenolate mofetil. [ABSTRACT FROM AUTHOR]

Background: Rapidly progressive glomerulonephritis (RPGN) is characterized by a rapid deterioration of renal function and by extracapillary proliferation in >50% of glomeruli. The most common type of RPGN is “pauci-immune” glomerulonephritis caused by anti-neutrophil cytoplasmic antibodies-associated vasculitis (AAV). Summary: The incidence of AAV increases with age and pauci-immune glomerulonephritis is the most common diagnosis found in renal biopsies in the elderly population. Age was identified as an independent negative risk factor for both death and end-stage renal disease in AAV, and the mortality of older patients was uniformly higher than in younger patients in all retrospective studies. Early diagnosis may be difficult particularly in elderly patients with renal-limited disease but is important for the good outcome of the patients. Immunosuppressive treatment options include cyclophosphamide or rituximab combined with corticosteroids with or without plasma exchange in case of severe disease. Data from randomized trials are completely missing for patient aged >75 years. Based on retrospective studies, elderly patients seem to respond to immunosuppressive drugs just as younger patients are able to, but they are at a higher risk of adverse events. Key Messages: RPGN is relatively common in the elderly patients. Immunosuppressive treatment in older patients with AAV or RPGN may be useful but needs to be strictly individualized with all the risks taken into consideration. Further studies are needed to examine the role of novel therapeutic options in the elderly population with RPGN. [ABSTRACT FROM AUTHOR]

As the population worldwide ages, the epidemic of kidney disease will also increase. Anti-neutrophil cytoplasmic antibodies (ANCA) positive rapidly progressive positive glomerulonephritis (RPGN) is the most common etiology for biopsied patients among the very elderly. Its pathological features and clinical course are well described, though there is still debate about the mechanism of injury involved in individual patients. From very ancient times, the cornerstone of treatment historically has been high-dose cyclophosphamide and a lengthy course of high-dose corticosteroids. Although this regimen has diminished the immediate mortality rate of RPGN, its intermediate and long-term adverse effects are not insignificant. Attempts to minimize toxicity and improve efficacy have been made through the years to allow physicians some options for therapy. Lower cumulative cyclophosphamide regimens, shorter corticosteroid courses, and the introduction of rituximab have modified the armamentarium for treatment of ANCA positive RPGN. As progress is made in understanding the molecular pathogenesis of this disease, new targets will be found for potential therapeutic attack. The complement system is an area of active interest for all glomerular diseases at this time. Indeed, animal studies and preliminary human studies suggest that targeting the complement system can ameliorate the course of ANCA-positive RPGN. Hopefully, as the population ages, we will see more and safer therapeutic options to treat this once rapidly fatal disease. [ABSTRACT FROM AUTHOR]

Autoimmune liver diseases (AILD) are a group of immunologically induced hepatic disorders that can lead to liver cirrhosis and end-stage liver disease. Extra-hepatic involvement and association with rheumatic diseases (such as Sjögren’s syndrome, systemic sclerosis and rheumatoid arthritis) are well known, whereas the coexistence of AILD with small-vessel vasculitis in the same patients have been only occasionally reported. In the present paper we report four such cases and an extensive review of the literature. Clinical features of autoimmune-liver diseases associated with small-vessel vasculitis are discussed, as well as possible common pathogenic pathways including HLA genomics, costimulatory molecules and autoantibodies. In conclusion, knowledge about this association can help physicians in recognising and treating an aggressive disease which could otherwise result in severe and multiple organ damage, compromising the overall prognosis and the indication to liver transplantation.

Autoantibody (autoAb) production in patients with systemic autoimmune diseases is a hallmark of disease entity, activity and prognosis. Although a large number of autoAbs have been discovered to date, there is a limited number of autoAbs whose pathogenic roles have been clearly determined. However, intriguing evidence has recently been provided of possible pathogenic roles for anti-neutrophil cytoplasmic Abs (ANCAs) against myeloperoxidase (MPO) in ANCA-associated vasculitides (AAV) and for anti-citrullinated protein Abs (ACPAs) in rheumatoid arthritis (RA). Of note, these autoAbs are thought to display both direct and indirect effects on organ failure. Additionally, some autoAbs have been reported to play pathogenic roles in brain damage in patients with neuropsychiatric systemic lupus erythematosus (NPSLE), which is one of the most refractory autoimmune disorders. Thus the binding of autoAbs to a certain sequence of the N-methyl-D-aspartate receptor subunit NR2 (anti-NR2 Abs) may directly induce hippocampal neuronal injury. On the other hand, anti-U1 ribonucleoprotein (RNP) Abs might be pathogenic by inducing neurotoxic inflammatory mediators intrathecally. Such autoAb measurements are also clinically meaningful for treatment selection.

Skin lesions are frequent manifestations of underlying systemic conditions, including systemic autoimmune vasculitis. In particular, anti-neutrophil cytoplasmic antibodies (ANCA) are associated with distinct forms of vasculitis characterized by inflammatory cell infiltration of the walls of small and medium-sized vessels leading to vascular destruction and tissue necrosis. ANCA-associated vasculitis is rare and systemic diseases, which can be classified based on different distribution of vascular inflammation and presence or absence of granulomatosis and asthma. Despite their diversities, ANCA-associated vasculitis, namely microscopic polyangiitis, granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis, can all display a broad variety of cutaneous manifestations, which can appear during the course of the disease or even as first sign at the time of onset. Different skin manifestations might coexist in the same patient and occur in different occasions during the course of the vasculitis. Thus, a deep knowledge of the spectrum of skin lesions as part of ANCA-associated vasculitis is mandatory for a correct diagnostic process, whenever cutaneous vasculitis is suspected. Due to this broad variety of manifestations, the diagnosis of skin involvement in ANCA-associated vasculitis is very challenging and it must be supported by a detailed medical history, accurate physical examination, specific histopathological analysis of skin biopsy and the presence of ANCA serology. In this review, we focus on the cutaneous manifestations that can develop in the context of ANCA-associated vasculitis, detailing the clinical features, the histopathological aspects as well as the direct immunofluorescence studies for each of the three conditions. Moreover, we acknowledged the differential diagnoses that must be ruled out in the diagnostic process and the main therapeutic approaches available for treatment of ANCA-associated vasculitis. [ABSTRACT FROM AUTHOR]

Objective. The objective of this multicentre study was to improve the clinical interpretation of PR3- and MPO-ANCAs as an adjunct for the diagnosis of ANCA-associated vasculitis (AAV) by defining thresholds and test result intervals based on predefined specificities and by calculating test result interval-specific likelihood ratios (LRs). Methods. Eight different PR3- and MPO-ANCA immunoassays from seven companies were evaluated using 251 diagnostic samples from AAV patients and 924 diseased controls. Results. Thresholds for antibody levels were determined based on predefined specificities (95, 97.5, 99 and 100%) and used to delimit test result intervals. Test result interval-specific LRs were determined. For all assays, the LR for AAV increased with increasing antibody level. For all but one immunoassay, high antibodies levels (associated with LR>55) were found in a substantial fraction (>65%) of patients. The area under the curve (AUC) of receiver operating characteristics analysis of a diagnostic approach in which positive results were confirmed by IIF or another immunoassay was not substantially higher than the AUC of performing immunoassay only. The highest AUC was found when immunoassay was combined with another immunoassay or with IIF. Conclusion. To diagnose AAV based on PR3- and MPO-ANCA, it is useful to define thresholds for antibody levels and to assign test result interval-specific LRs. Higher antibody levels are associated with a higher likelihood for disease. Such information improves clinical interpretation. [ABSTRACT FROM AUTHOR]

Background Testing for autoantibodies to myeloperoxidase (MPO) and proteinase 3 (PR3) is part of anti-neutrophil cytoplasmic antibodies (ANCA) test that aids the diagnosis of a number of autoimmune diseases including small-vessel vasculitis. We characterized the differences between two automated immunoassays at three facilities for measuring MPO- and PR3-ANCA autoantibodies. Methods 117 serum samples were analyzed for MPO and PR3 autoantibodies. The INOVA QUANTA Lite® IgG assay (INOVA Diagnostics) were performed at two facilities and the Bio-Plex® 2200 Vasculitis Panel (Bio-Rad) were performed at a third reference lab. The results were compared both qualitatively (between INOVA QUANTA Lite® and Bio-Plex® methods) and quantitatively (between two sites performing INOVA QUANTA Lite® assays). Results Comparison of the INOVA QUNATA Lite® assays at two different facilities (n = 36) demonstrated high concordance (97.2% for MPO and 94.4% for PR3) and quantitative correlation (R 2 = 0.973 for MPO and R 2 = 0.935 for PR3). Conversely, INOVA QUNATA Lite® and Bio-Plex® methods showed poor concordance at 70.4% for MPO (n = 81; 95% CI: 59.7% to 79.2%) and at 76.5% for PR3 (n = 81; 95% CI: 66.2% to 84.4%). Conclusion This study demonstrated low concordance between two methods for MPO-ANCA and PR3-ANCA measurements. Given the discrepancies, the performance of different autoantibody immunoassay methods should be taken into consideration when evaluating MPO-ANCA and PR3-ANCA results. [ABSTRACT FROM AUTHOR]

Aim Anti-neutrophil cytoplasmic antibodies ( ANCA) are associated with small vessel vasculitis now termed ' ANCA associated vasculitis' ( AAV). ANCAs are reported in diverse diseases where they have no clinical utility. We carried out an audit in a clinical immunology laboratory and assessed if use of ordering practices could have improved utility of ANCA. Methods All samples received for ANCA testing during 2014 were tested by indirect immunofluorescence ( IIF) and automated enzyme-linked immunosorbent assay ( ELISA). Clinical records of all samples positive by one or more assays were retrieved. We assessed the effect of applying proposed test ordering guidelines on performance of the tests. Results Of 1590 samples, 108 (6.8%) had a positive result by at least one method. IIF showed perinuclear pattern in 72 (21 were antinuclear antibody positive), cytoplasmic in 22, six had atypical pattern and eight were negative. By ELISA anti-myeloperoxidase antibodies were present in 33 samples, anti-proteinase 3 in 24, while five sera had both antibodies. ELISA and IIF were concordant in 45 samples. Twenty-seven patients had AAV of which 23 were both ELISA and IIF positive. Among these 27 with AAV all had at least one ordering criteria, while in 81 patients without AAV but with positive test, 38 had no ordering criteria. Conclusion Reduction in false positive can be achieved by considering only those samples as ANCA positive that test positive both on IIF and ELISA and by following ordering guidelines before requesting ANCA testing, and by use of ordering criteria by clinicians. [ABSTRACT FROM AUTHOR]

Résumé La consommation de cocaïne est un piège étiologique récurrent dans le champ des vascularites systémiques. Dès les années 1990 a été soulevée la possibilité de survenue de lésions ORL mimant une granulomatose avec polyangéite localisée accompagnées d’anticorps anti-cytoplasme des polynucléaires neutrophiles (ANCA), dirigés contre la protéinase 3 (PR3) et la human neutrophil elastase (HNE). Plus récemment, la cocaïne coupée au lévamisole a été responsable, en Amérique du Nord puis dans le reste du monde, de multiples cas de vasculopathie cutanées voire systémiques associées à des ANCA, avec fréquemment une double positivité, anti-myéloperoxydase et anti-PR3, et d’autres auto-anticorps. Les particularités cliniques et immunologiques de ces tableaux toxiques doivent être connues. La physiopathologie de ces affections reste imparfaitement élucidée mais pourrait nous permettre de mieux comprendre les mécanismes de la rupture de tolérance à l’œuvre dans les vascularites à ANCA classiques. Cocaine use is a multifaceted diagnostic pitfall in the field of systemic vasculitides. The fact that Cocaine-Induced Midline Destructive Lesions (CIMDL) can be associated with Anti-Neutrophil Cytoplasmic Antibodies (ANCA) and mimic localized granulomatosis with polyangitis is known for decades. In these cases ANCA target Proteinase 3 (PR3) and Human Neutrophil Elastase. More recently, levamisole adulterated cocaine has been implicated in a peculiar clinico-biological syndrome combining cutaneous vasculopathy and sometimes glomerulonephritis, and ANCA positivity with frequent double positivity (PR3 and myeloperoxydase). Clinician should be aware of the clinical and immunological hints to these diagnoses. The pathogenesis of such drug-induced auto-immune syndromes is poorly understood. Its studying may shed new light on the potential mechanism involved in tolerance breakdown in conventional ANCA-associated vasculitides. [ABSTRACT FROM AUTHOR]

Neutrophil extracellular traps (NETs) are chromatin filaments decorated with enzymes from neutrophil cytoplasmic granules. Anti-neutrophil cytoplasmic antibodies (ANCAs) bind to enzymes from neutrophil cytoplasmic granules and are biomarkers for the diagnosis of systemic vasculitides. ANCA diagnostics are based on indirect immunofluorescence (IIF) of ethanol-fixed neutrophils. IIF shows a cytoplasmic staining pattern (C-ANCA) due to autoantibodies against proteinase 3 (PR3) or a perinuclear staining pattern (P-ANCA) due to autoantibodies against myeloperoxidase (MPO). The distinct ANCA-staining patterns are an artifact of ethanol fixation. Here, we tested NETs as a substrate for the detection of ANCAs in human sera. We observed that P-ANCAs specifically stained NETs, while C-ANCAs targeted the cell bodies of netting neutrophils. The distinct ANCA-staining patterns were caused by the presence of MPO, but not PR3, in NETs. Using NETs as a substrate for IIF, we characterized ANCAs in sera of patients with ANCA-associated vasculitis (AAV). Furthermore, we inhibited serine proteases by diisopropylfluorophosphate to prevent chromatin unfolding and the release of NETs and thus generated neutrophils with MPO-positive nuclei and PR3-positive cytoplasm, which resembled the appearance of ethanol-fixed neutrophils. In conclusion, our data suggest that NETs are selectively loaded with antigens recognized by P-ANCAs and netting neutrophils provide a physiological substrate for ANCA detection in patients with AAV. [ABSTRACT FROM AUTHOR]

Anti-neutrophil cytoplasmic antibodies (ANCA) appear to play an important role in the pathogenesis of ANCA-associated vasculitis (AAV). However, ANCA alone are not sufficient to generate disease, and some evidence suggests that infectious triggers may serve as inciting events for AAV disease activity. Antibodies of the immunoglobulin (Ig)M isotype often serve as markers of recent infection, and IgM ANCA have been identified previously in patients with AAV, although the frequency and clinical relevance of IgM ANCA is not well established. We sought to characterize IgM ANCA more clearly by creating a novel enzyme-linked immunosorbent assay (ELISA) for IgM antibodies to proteinase 3 [IgM proteinase 3 (PR3)-ANCA], which we applied to two large, clinically well-characterized trial cohorts of patients with granulomatosis with polyangiitis and microscopic polyangiitis. In the first cohort, IgM PR3-ANCA occurred with a frequency of 15·0%, and were associated with a higher degree of disease severity and a trend towards a higher rate of alveolar haemorrhage (29·6 versus 15·7%, P = 0·10). Analysis of follow-up samples in this cohort showed that the presence of IgM PR3-ANCA was transient, but could recur. In the second cohort, IgM PR3-ANCA occurred with a frequency of 41·1%, and were also associated with a higher degree of disease severity. A higher rate of alveolar haemorrhage was observed among those with IgM PR3-ANCA (45·3 versus 15·8%; P < 0·001). The association of transient IgM PR3-ANCA with an acute respiratory manifestation of AAV suggests a possible link between an infectious trigger and AAV disease activity. [ABSTRACT FROM AUTHOR]

Chronic pulmonary infection is a hallmark of cystic fibrosis (CF) and requires continuous antibiotic treatment. In this context, Pseudomonas aeruginosa ( Pa ) is of special concern since colonizing strains frequently acquire multiple drug resistance (MDR). Bactericidal/permeability-increasing protein (BPI) is a neutrophil-derived, endogenous protein with high bactericidal potency against Gram-negative bacteria. However, a significant range of people with CF (PwCF) produce anti-neutrophil cytoplasmic antibodies against BPI (BPI-ANCA), thereby neutralizing its bactericidal function. In accordance with literature, we describe that 51.0% of a total of 39 PwCF expressed BPI-ANCA. Importantly, an orthologous protein to human BPI (huBPI) derived from the scorpionfish Sebastes schlegelii (scoBPI) completely escaped recognition by these autoantibodies. Moreover, scoBPI exhibited high anti-inflammatory potency towards Pa LPS and was bactericidal against MDR Pa derived from PwCF at nanomolar concentrations. In conclusion, our results highlight the potential of highly active orthologous proteins of huBPI in treatment of MDR Pa infections, especially in the presence of BPI-ANCA., Competing Interests: JH, MT, MW, KE, HS, DP, SB, NG, CB No competing interests declared, AG, SB The University of Regensburg is applying for a patent (PCT/EP2022/087280) covering parts published in this manuscript with André Gessner and Sigrid Bülow as inventors, (© 2023, Holzinger et al.)

Granulomatosis with polyangiitis (GPA) is a necrotizing vasculitis of small and medium-sized vessels comprising inflammation of the vessel wall and perivascular and extravascular granulomas, frequently presenting in the form of chronic sinusitis. We report the case of a 27-year-old man who presented with very painful acute frontal sinusitis that was managed medically and surgically. The symptoms rapidly recurred despite treatment and CT scan demonstrated diffuse thickening of the sinus mucosa. Anti-proteinase 3 ANCA were positive. Biopsy of a pulmonary nodule confirmed the diagnosis of GPA. The patient was treated with corticosteroids in combination with rituximab, resulting in improvement of the clinical, laboratory and CT signs. In the presence of persistent, acute, localized sinusitis despite appropriate treatment, associated systemic signs and/or the presence of other signs suggestive of GPA, the ENT surgeon must request a targeted work-up. In the absence of treatment, GPA can be fatal within a few months. However, with currently available treatment, remission is obtained in 80% of cases with a 75% 10-year survival rate. [ABSTRACT FROM AUTHOR]

Background: Anti-neutrophil cytoplasmic antibodies are serological markers of primary systemic vasculitis. Antigen-specific tests such as ELISA to detect antibodies directed against the myeloid enzymes, MPO and PR3 are essential in addition to screening by indirect immunofluorescence. Study was undertaken to 1) evaluate the diagnostic value of ANCA measurement by IIF, coupled with reflex anti-PR3 (for c-ANCA) and anti- MPO (for p-ANCA) ELISA for ANCA positive specimens, and 2) evaluate the utility of testing specimens simultaneously by all 3 tests, i.e. IIF, MPO and PR3 ELISA. Methods: The study was a retrospective study performed at a CAP and NABL accredited private reference laboratory in Mumbai in a community setting. A total of 23,920 serum specimens from patients with suspected small vessel vasculitis were tested for ANCA by IIF over a period of 5½ years. Of these, 855 specimens (3.57%) (Group I) had a pre request for anti-MPO or anti-PR3 ELISA following a positive IIF-pANCA pattern or IIF cANCA pattern respectively. Group II comprised another 52 specimens which had a pre-request for all 3 tests i.e. IIF, MPO and PR3 ELISA simultaneously, irrespective of the IIF positivity. Results: ANCA seroprevalence was 31.11% in group I with predominant p- ANCA pattern (65.41%). p-ANCA was more frequent in females and c-ANCA in males. Anti-MPO and anti-PR3 positivity was 23.56% and 36.95% respectively, highlighting the non-specific nature of IIF-ANCA. Anti-MPO & anti-PR3 positivity was lower in females (21.10% and 31.70%, respectively) as compared to males (27.69% and 41.17%, respectively). Simultaneous performance of the three tests in Group II did not yield any significant advantage over reflex testing. Conclusion: Utility of reflex testing of IIF-ANCA positive specimens to MPO/PR3 ELISA is re-inforced in the Indian population. However, test requests for using the reflex algorithm are low. Prescribers must thus be encouraged to follow the reflex algorithm for patient benefit.

Sjögren's syndrome is a chronic autoimmune disease, characterized by specific autoimmune antibodies anti-Ro and anti-La, and it can involve multiple organs, such as the kidneys, lungs, muscles, and nervous system. The most common renal complication of Sjögren's syndrome is tubulointerstitial nephritis, and glomerulonephritis is relatively uncommon. We report the case of an 86-year-old man presenting with recurrent fever, poor appetite, decreased salivary secretion, and body weight loss. Laboratory investigation revealed that serum creatinine was 4.2 mg/dL, proteinuria was 3+, and there was microscopic hematuria. Positive perinuclear anti-neutrophil cytoplasmic antibody, anti-Ro, and anti-La antibodies were detected. Renal biopsy showed crescentic glomerulonephritis with scanty immune complex deposition. The patient was diagnosed with primary Sjögren's syndrome complicated with rapidly progressive glomerulonephritis with positive anti-neutrophil cytoplasmic antibody. Unlike the patients of other case reports, our patient's renal function did not recover after immunosuppressant treatment, and he finally received long-term hemodialysis. Pauci-immune glomerulonephritis is a rare renal complication of Sjögren's syndrome, and progress to renal failure in such patients is possible.

Background: Advances in long-term parenteral nutrition via indwelling central venous catheter have improved the quality of life and mortality in patients with life-threatening gastrointestinal diseases complicated with severely impaired absorption. However, infection to central venous catheter is still a common and critical complication for such patients. We encountered two patients under long-term parenteral nutrition who developed glomerulonephritis associated with central venous catheter infection. Persistent bacterial infection in indwelling medical devices placed in the blood-stream such as a ventricular-atrial shunt is known to cause glomerulonephritis, a condition termed shunt nephritis. We reported the clinical manifestations, treatment and their pathological findings in the two patients with glomerulonephritis associated with central venous catheter infection. Case presentation: Both patients suffered from megacystis microcolon intestinal hypoperistalsis syndrome, a form of pseudo-Hirschsprung's disease. They had been receiving home parenteral nutrition via central venous catheter because of severe malabsorption. They presented proteinuria, hematuria, hypocomplementemia and positive PR3- antineutrophilic cytoplasmic antibody accompanied by Staphylococcus epidermidis infection in the central venous catheter. Their renal biopsy revealed membranoproliferative glomerulonephritis with positive C3 deposition. One of them recovered completely following the removal of catheter and administration of antibiotics, while another did not respond to the treatments. We then treated her with methylprednisolone pulse therapy followed by prednisolone. She responded well, and achieved complete remission. Conclusion: As central venous catheter infection-related glomerulonephritis has a similar etiology to shunt nephritis, removal of the catheter and administration of antibiotics is fundamental to the treatment. If a patient is resistant to such conventional therapy, additional steroid and/or immunosuppressive agent could be considered. Although the number of patients with classical shunt nephritis is decreasing since the ventricular-peritoneal shunt has become became the major procedure for hydrocephalus, central venous catheter infection-related glomerulonephritis may increase in the future due to a marked increase in the number of patients receiving long-term parenteral nutrition. Routine urinalysis should be considered in such patients for early detection of central venous catheter infectionrelated glomerulonephritis. [ABSTRACT FROM AUTHOR]

Anti-neutrophil cytoplasmic antibody-associated vasculitis is an uncommon inflammatory disease of small to medium-sized vessels that frequently presents with rapidly progressive glomerulonephritis and renal failure though it can affect any organ system. If untreated, the vast majority of patients will die within a year. Current treatments improve prognosis but affected patients remain at a substantially higher risk of death and adverse outcomes. We review the classification of the disease, our understanding of the pathogenesis and epidemiology, and propose future directions for research. We also evaluate the evidence supporting established treatment regimens and the progress of clinical trials for newer treatments to inform the design of future studies. [ABSTRACT FROM AUTHOR]

ANCA-associated vasculitides (AAV) are chronic autoimmune diseases characterized by inflammation and destruction of small vessels. Rituximab is now licensed for use as a remission-induction agent in the treatment of these disorders. During recent years, several non-controlled studies have suggested that rituximab may be of value in maintaining disease remission in AAV. In these series, 3 techniques have been tried: "watch-and-wait", repeated cycles in fixed intervals, or administration based on proposed biomarkers. More importantly, the results of the MAINRITSAN trial showed that this anti-CD20 agent is superior to azathioprine for preventing major relapses in AAV. This review summarizes current information regarding the effectiveness, timing, dosing, duration and safety o1f rituximab as a valid option for remission maintenance. [ABSTRACT FROM AUTHOR]

Objective. To study the role of deoxyribonuclease (DNase) I activity and ANCA in propylthiouracil (PTU)-induced lupus-like syndrome (LLS). Methods. We compared 36 SLE patients with 17 PTU-induced LLS patients diagnosed from 2008 to 2014. We studied ANCA profile (MPO, PR3, lactoferrin, CTG, elastase, bactericidal/permeability-increasing protein), anti-dsDNA, anti-ENA, anti-nucleosome, anti-histone, anti-C1q, anti-aCL, complement components, cryoglobulins and serum DNase I activity. Healthy persons and patients without LLS treated with PTU comprised the control groups. Twelve LLS patients were serologically and clinically followed for 4.1 (S.D. 2.0) years. Results. PTU-induced LLS patients less frequently had arthritis, renal and neurological manifestations, but more frequently had fever, purpura, urticarial-like vasculitis and ulceration (P<0.01). PTU-induced LLS patients more frequently had polyspecific ANCA (anti-MPO, anti-elastase and anti-PR3 were most commonly detected) (P<0.01). SLE patients more frequently had anti-dsDNA, anti-ENA, anti-nucleosome, anti-C1q (P<0.01) and anti-histone antibodies (P<0.05). PTU-induced LLS patients had lower DNase I activity than SLE patients and controls (P<0.01). Discontinuation of PTU increased DNase I activity, although it did not reach the levels of controls (P<0.01). After remission, MPO-ANCA decreased (P<0.01), but persisted for a long time. Conclusion. PTU, as a trigger, and low DNase I activity, as a predisposing factor, may lead to LLS. Polyspecific ANCAs are useful markers for differentiating SLE from PTU-induced LLS. Low DNase I activity might be an important prognostic biomarker for PTU-induced LLS. Monitoring of ANCA and DNase I activity may prevent long-lasting exposure to causal drugs, unnecessary immunosuppressive therapy and severe complications of LLS. [ABSTRACT FROM AUTHOR]

Objectives. Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a disease with significant ethnic differences. Reports on characteristics of Japanese granulomatosis with polyangiitis (GPA) patients are limited, and this study was undertaken to determine the characteristics of Japanese GPA patients. Methods. This was a retrospective chart study of 24 Japanese GPA patients. GPA was defined according to the European Medicines Agency algorithm. Results. The percentage of MPO-ANCA-positive patients was 33.3%, higher than the percentages reported in studies from Western countries. MPO-ANCA-positive GPA patients differed from PR3-ANCA-positive GPA patients in organs involved at diagnosis with MPO-ANCA-positive patients having nose and sinus involvement less frequently compared to PR3-ANCA-positive patients. Interstitial lung infiltrates were more common among MPO-ANCA-positive GPA patients compared to PR3-ANCA-positive GPA patients. Conclusion. Among Japanese GPA patients, the proportion of MPO-ANCA-positive patients is higher compared to reports from Western countries, and those patients are often different from the classical picture of GPA. [ABSTRACT FROM AUTHOR]

In this article, we present a case of a female patient suffering from granulomatosis and polyangiitis with active glomerular disease, who developed exacerbation of pulmonary vasculitis and palpable tumors of right breast. A possibility of neoplastic disease was excluded by histopathological examination of percutaneous biopsy specimen, revealing granulomatous inflammatory infiltrate, without any features of neoplasia. Moreover, both pulmonary and breast lesions subsided following intensification of immunosuppressive/antiinflammatory treatment. [ABSTRACT FROM AUTHOR]

Objective. We conducted a cross-sectional nationwide survey to determine eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (EGPA) prevalence and clinical features in Japan. Methods. Data for EGPA patients in 2008 were collected from 1,564 hospitals. In total, 965 patients were reported from 365 departments. In a second survey, clinical data for 473 patients were obtained. Results. We estimated that 1,866 (95% CI: 1,640-2,092) patients have EGPA in Japan (prevalence, 17.8/1,000,000). Of the 473 patients in the second survey, 315 fulfilled American College of Rheumatology (ACR) criteria or Lanham's criteria for EGPA. The mean age (± SD) of the 315 at onset was 55 ± 14 years, male to female ratio 1:2. 93% of patients had neurological manifestations, which were the organ system most frequently involved. Among 277 patients tested for myeloperoxidase (MPO)-/p anti-neutrophil cytoplasmic antibody (ANCA), 139 (50%) were positive, while only 6 of 238 were positive for proteinase3 (PR3)-/cANCA. MPO-ANCA-positive patients had renal involvement, mucous membrane or ophthalmological symptoms, and ENT symptoms more frequently, whereas cutaneous lesions and cardiovascular involvement were less common. Conclusion. The prevalence of EGPA and the frequency of MPO-/p-ANCA-positivity in Japanese EGPA patients were mostly similar to those of Western countries. However, female predominance and a high frequency of neurological manifestations characterized Japanese patients. [ABSTRACT FROM AUTHOR]

Abstract: Anti-endothelial cell antibodies (AECAs) have been reported to cause endothelial cell dysfunction, but their specific targets have never been identified in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs). Proteins from human umbilical vein endothelial cells (HUVECs) were separated by 2-dimensional electrophoresis (2-DE). 2-D immunoblots were used to compare serum IgG reactivities from 30 patients with AAV and 12 healthy controls (HCs). Proteins identified as target antigens by MALDI- TOF-TOF mass spectrometry included lamin A/C, vimentin, α-enolase, far upstream binding protein 2 (FUBP2) and protein disulfide-isomerase A3 precursor (PDIA3). Antibodies targeting lamin A, vimentin, α-enolase, FUBP2 and PDIA3 were identified in 57.1%, 64.3%, 35.7%, 50% and 0% of patients with microscopic polyangiitis and 8%, 3.3%, 7.2%, 0% and 6.7% of HCs respectively. IgG from patients with microscopic polyangiitis had stronger reactivity against HUVEC than other groups and HCs and induced stronger Erk phosphorylation in HUVECs than IgG from HCs. [Copyright &y& Elsevier]

Autoimmune liver diseases (AILD) are a group of immunologically induced hepatic disorders that can lead to liver cirrhosis and end-stage liver disease. Extra-hepatic involvement and association with rheumatic diseases (such as Sjögren's syndrome, systemic sclerosis and rheumatoid arthritis) are well known, whereas the coexistence of AILD with small-vessel vasculitis in the same patients have been only occasionally reported. In the present paper we report four such cases and an extensive review of the literature. Clinical features of autoimmune-liver diseases associated with small-vessel vasculitis are discussed, as well as possible common pathogenic pathways including HLA genomics, costimulatory molecules and autoantibodies. In conclusion, knowledge about this association can help physicians in recognising and treating an aggressive disease which could otherwise result in severe and multiple organ damage, compromising the overall prognosis and the indication to liver transplantation. [ABSTRACT FROM AUTHOR]

The use of diagnostic testing in the clinical practice of medicine has been a shifting landscape from the time that the first blood test was utilized. This is no different in the field of immunology and in particular rheumatology. As the field of immunology is relatively young, the clinical tests are not well established and therefore guidelines for use are still under debate. In this review, we seek to look at some of the key autoantibodies, as well as other tests that are available to diagnose suspected rheumatologic disease, and examine how to best use these tests in the clinic. In particular, we will focus on the anti-nuclear antibodies, anti-neutrophil cytoplasmic antibodies, complement, cryoglobulins, rheumatoid factor, and anti-citrullinated protein antibodies. [ABSTRACT FROM AUTHOR]