Presence Of Antineutrophil Cytoplasmic Autoantibodies Research Articles

The Presence of ANCA in IgA Crescentic Nephropathy Does Not Lead to Worse Prognosis with Intensive Rescue Treatment

Immunoglobulin A nephropathy (IgAN) is the most common glomerulonephritis worldwide. The concomitant presence of both crescentic proliferation and anti-neutrophil cytoplasmic autoantibodies (ANCA) in this pathology represents a rare coincidence. However, it is not clear to what extent the presence of ANCA (IgA or IgG) in these patients could have any clinical significance. The aim of the current work is to describe the presence of ANCA (IgA or IgG) in patients with IgAN and crescentic proliferation and its possible clinical implications. We retrospectively recruited all patients in our center with a histological diagnosis of IgAN with crescentic proliferation between January 2013 and December 2020. The main demographic and clinicopathologic data, fundamental histological characteristics, as well as the treatments implemented and main kidney outcomes, were collected and analyzed at a 6 and 12-month follow-up. Between January 2013 and December 2020, a total of 17 adults were diagnosed with concomitant crescentic proliferation through a kidney biopsy of IgAN. Five (29.4%) patients showed ANCA, three (60%) showed IgA-ANCA and two (40%) showed IgG-ANCA. All ANCA-positive patients had some degree of crescentic proliferation. At diagnosis, the mean age of patients was 48 years old (range: 27-75). Nine of them were women (52%) and the most common clinical presentation was hypertension (71%). At the time of biopsy, the mean serum creatinine and proteinuria were 2.2 mg/dL (DS 1.42) and 3.5 g/mgCr (DS 1.22), respectively, with no statistical differences between ANCA-positive and -negative patients. Histological analyses showed that 11 out of the 12 (91%) ANCA-negative IgAN patients displayed less than 25% cellular crescents, whereas 100% of ANCA-positive IgAN patients displayed more than 25% cellular crescents (p = 0.04). Notably, five (30%) patients displayed fibrinoid necrosis, with four of them (80%) being IgAN-ANCA-positive (p = 0.01). Only one ANCA-negative patient needed renal replacement therapy (RRT) upon admission (5%). The mean serum creatinine and proteinuria were 1.94 mg/dL (DS 1.71) and 1.45 g/gCr (DS 1.78), respectively, within 6 months of immunosuppressive therapy. At 12-month follow-up, the mean creatinine was 1.57 mg/dL (DS 1). Four (23.5%) patients needed RRT at the end of the follow-up and four (23.5%) patients died. Probably due to the limited number of IgAN-ANCA-positive and IgAN-ANCA-negative patients, no significant differences were found between the clinical and laboratory characteristics. IgAN-ANCA-negative patients seemed to display less extracapillary proliferation than IgAN-ANCA-positive patients, who tended to show significantly higher fibrinoid necrosis. There were no differences regarding renal prognosis and patient survival after aggressive immunosuppressive therapy within 6 and 12 months when comparing the two samples.

Vasculitis in Cystic Fibrosis.

Cystic fibrosis (CF) is an autosomal-recessive multi-organ disease characterized by airways obstruction, recurrent infections, and systemic inflammation. Vasculitis is a severe complication of CF that affects 2–3% of CF patients and is generally associated with poor prognosis. Various pathogenic mechanisms may be involved in the development of CF-related vasculitis. Bacterial colonization leads to persistent activation of neutrophilic granulocytes, inflammation and damage, contributing to the production of antineutrophil cytoplasmic autoantibodies (ANCAs). The presence of ANCA may on the other hand predispose to bacterial colonization and infection, likely entertaining a vicious circle amplifying inflammation and damage. As a result, in CF-associated vasculitis, ongoing inflammation, immune cell activation, the presence of pathogens, and the use of numerous medications may lead to immune complex formation and deposition, subsequently causing leukocytoclastic vasculitis. Published individual case reports and small case series suggest that patients with CF-associated vasculitis require immune modulating treatment, including non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, hydroxychloroquine, and/or disease-modifying anti-rheumatic drugs (DMARDs). As immunosuppression increases the risk of infection and/or malignancy, which are both already increased in people with CF, possible alternative medications may involve the blockade of individual cytokine or inflammatory pathways, or the use of novel CFTR modulators. This review summarizes molecular alterations involved in CF-associated vasculitis, clinical presentation, and complications, as well as currently available and future treatment options.

ANCA-associated vasculitis in a 14 years-old patient: a clinical case

Background. ANCA-associated systemic vasculitis is a rare childhood disease. Antineutrophil cytoplasmic autoantibodies (ANCA)-related vasculitises include microscopic polyangiitis, granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis. Their rarity often leads to a late diagnosis, rapid disability and high mortality in patients due to aggressive respiratory, pulmonary lesion and renal failure.Clinical Case Description. The patient suffered from a recurrent bronchoobstructive syndrome with signs of respiratory failure, obscure origin fever and chronic rhinitis with nasal bleeding for 6 months. The patient was diagnosed with obstructive bronchitis (putative bronchial asthma debut), received antibacterial therapy and inhalation bronchodilators without stable improvement during the entire period. Skin haemorrhages and arthralgia stimulated diagnostic research to establish ANCA-associated systemic vasculitis (presence of proteinase 3-specifi c ANCAs in titre 1/80). CT lung scanning revealed frosted glass foci of reduced pulmonary pneumatisation and signs of bilateral bronchoobstruction. Immunosuppressive therapy with glucocorticosteroids (methylprednisolone pulse therapy No. 3, 1000 mg intravenously on alternate days, subsequent per os administration of 1 mg/kg/day) and cyclophosphamide (500 mg intravenously once per 28 days) was prescribed. This led to the positive dynamics with eliminated fever and skin haemorrhages, as well as essentially reduced signs of respiratory failure.Conclusion. Diagnosis of systemic vasculitis is often complicated and long-term due to commonly non-specifi c debut symptoms of autoimmune disorders. In the described case, the fi rst 6 months of illness displayed intoxication and bronchoobstruction with signs of respiratory failure. Haemorrhagic rashes, arthralgias and the presence of ANCAs are proxy to vasculitis. Standard immunosuppressive therapy for ANCA-associated vasculitis improved the patient’s condition.

The net effect of ANCA on neutrophil extracellular trap formation

The formation of neutrophil extracellular traps induced by antineutrophil cytoplasmic autoantibodies has been implicated in the pathogenesis of antineutrophil cytoplasmic autoantibody-associated vasculitis. Kraaij etal. now provide evidence that excessive neutrophil extracellular trap formation invitro induced by sera from patients with antineutrophil cytoplasmic autoantibody-associated vasculitis is associated with active disease but is not dependent on the presence of antineutrophil cytoplasmic autoantibodies.

Refining phenotypes in ANCA-associated vasculitis

As granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) share histopathologic and clinical features, including the presence of antineutrophil cytoplasmic autoantibodies (ANCAs), patients with these syndromes are commonly labelled as having ANCA-associated vasculitis (AAV) and are subjected to similar treatments. A recent study suggests that dividing AAV into five classes based on disease phenotype provides better prognostic information than the classic division into GPA and MPA.

Pathogenesis of Lung Vasculitis

Vasculitides that affect the lung represent a diverse group of diseases with various systemic clinical manifestations, and include microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA, formerly Wegener granulomatosis), Churg-Strauss syndrome (CSS), and anti-glomerular basement membrane (anti-GBM) disease (Goodpasture syndrome). The etiologies of these diseases remain largely unknown. Although the pathogenic mechanisms of each differ, these diseases overlap by the presence of anti-neutrophil cytoplasmic autoantibodies in the vast majority of patients with MPA and GPA, and a substantial minority of patients with CSS and anti-GBM disease. This article reviews the current understanding of the pathogenesis of these four disease entities.

ANCA-Associated Lung Fibrosis

The possible link between pulmonary fibrosis, anti-neutrophil cytoplasmic autoantibody (ANCA) positivity, and vasculitis is poorly understood. During the past 6 years, five retrospective case-control studies have been published. These studies suggest that pulmonary fibrosis (PF) is an underestimated manifestation of ANCA-associated vasculitis. Common clinical characteristics include older age (around 70 years), constant positivity of myeloperoxidase (MPO)-ANCA and the poor prognosis of the pulmonary disease. The diagnosis of PF often predates the development of vasculitis. There are no significant differences of pulmonary function parameters, bronchoalveolar lavage analysis, or high-resolution computed tomographic (HRCT) findings between ANCA-associated PF and idiopathic pulmonary fibrosis (IPF). The high mortality rate of ANCA-associated PF indicates that a search for ANCAs should be performed at diagnosis in every patient with PF because the presence of ANCAs increases the risk of development of vasculitis and should promote specific monitoring of patients with positive MPO-ANCA.

Unexpectedly difficult intubation caused by subglottic stenosis in Wegener’s granulomatosis

A 76-year-old woman was scheduled to undergo abdominal aortic repair for progressive abdominal aortic aneurysm. After inducing general anesthesia, the 7.5-mm internal diameter (ID) tracheal tube could not be advanced below the level of the vocal cords because of resistance, and intubation was re-attempted several times using smaller tubes. An otolaryngologist was consulted and subglottic stenosis of unknown origin was suggested. The aortic repair was cancelled and tracheostomy was performed instead. She was diagnosed with Wegener's granulomatosis 46 days after the operation because she developed symptoms of renal dysfunction, hemoptysis, gastrointestinal bleeding, and presence of anti-neutrophil cytoplasmic autoantibodies (c-ANCA). The patient was treated with steroids but died 89 days after the operation because of pulmonary bleeding and renal dysfunction. Tracheal stenosis is a rare presenting feature of Wegener's granulomatosis that usually occurs late in the disease; however, anesthesiologists around the world need to bear in mind that the disease can present airway symptoms and can be the cause of airway obstruction.

Is Presence of ANCA in Crescentic IgA Nephropathy a Coincidence or Novel Clinical Entity? A Case Series

There are few anecdotal reports of circulating antineutrophil cytoplasmic autoantibodies (ANCAs) in patients with immunoglobulin A (IgA) nephropathy. Retrospective case series. We studied 8 patients with crescentic IgA nephropathy associated with ANCAs against myeloperoxidase (n = 5) and proteinase 3 (n = 3) followed up for 2.4 +/- 1.7 years. They were compared with 26 patients with IgA nephropathy with > 10% crescentic glomeruli, but negative for ANCAs. We analyzed clinical and histologic features of patients and their response to treatment. Screening for ANCAs was performed using indirect immunofluorescence, and positive results were verified using enzyme-linked immunosorbent assay. All patients with crescentic IgA nephropathy and positive for ANCAs, compared with only one-third of ANCA-negative patients, presented with the clinical syndrome of rapid progressive glomerulonephritis. ANCA-positive patients reached a higher peak serum creatinine level within the first 3 months (4.2 +/- 2.2 vs 2.5 +/- 1.9 mg/dL; estimated glomerular filtration rate, 19.3 +/- 10.2 vs 45.9 +/- 30.1 mL/min/1.73 m(2)). ANCA-positive patients with IgA nephropathy had a higher percentage of crescentic glomeruli (54.3% +/- 18%) compared with ANCA-negative patients with crescentic IgA nephropathy (34.5% +/- 26%). ANCA-positive patients were treated using cyclophosphamide and corticosteroids. Kidney function improved in all these patients: serum creatinine level decreased from the peak of 4.2 +/- 2.2 to 1.7 +/- 0.7 mg/dL at the end of follow up (estimated glomerular filtration rate, 19.3 +/- 10.2 to 44.6 +/- 11.1 mL/min/1.73 m(2)). In contrast, no significant improvement was achieved in ANCA-negative patients. Patients with IgA nephropathy, crescents, and positive for ANCAs represent a clinical entity with a diverse more exaggerated clinical and histologic picture. However, disease in these patients responded well to aggressive immunosuppressive therapy.

Activation, Apoptosis, and Clearance of Neutrophils in Wegener's Granulomatosis

Wegener's granulomatosis (WG) is strongly associated with the presence of antineutrophil cytoplasmic autoantibodies (ANCAs). Within WG these ANCAs are usually (80-90%) directed against the azurophilic enzyme proteinase 3, the so called PR3-ANCA. A pathophysiological role for these autoantibodies, supported by numerous in vitro and in vivo studies, is specifically based on their capacity to bind and activate neutrophils and potentially may damage vessels. In this review, the pathogenic potential of different developmental stages of the neutrophil in the pathogenesis of WG is discussed. After release from the bone marrow into the circulation, neutrophils can be primed by TNFalpha and become attached to locally activated endothelium. Once attached to the endothelium, ANCAs can fully activate these primed neutrophils. In this activation process, the degree of activation after stimulation with PR3-ANCAs associates with the level of PR3 expression on the membrane of the neutrophil. Following activation, infiltrated neutrophils become apoptotic with further membrane expression of PR3. In WG patients, clearance of apoptotic neutrophils can be disturbed due to the opsonization of PR3-expressing apoptotic neutrophils with PR3-ANCAs, thereby perpetuating inflammation by the release of proinflammatory cytokines during clearance; or it may favor autoimmunity by PR3 presentation in an inflammatory environment. Furthermore, the presence of ANCAs and the release of the vessel-related pentraxin PTX3 may lead to the persistence of late apoptotic neutrophils in tissues, thereby inducing leukocytoclastic lesions that are characteristic in patients with WG. All together, alive neutrophils as well as apoptotic neutrophils play a key role in different inflammatory phenomena seen in patients suffering from WG.

Occupational exposure in ANCA-positive patients: A case-control study

Antineutrophil cytoplasmic autoantibodies (ANCA) are valuable biomarkers for the diagnosis and follow-up of small vessel vasculitis. The role of ANCA has not yet been fully established, but genetic, infectious, and/or environmental factors may increase susceptibility to these diseases. We performed an epidemiologic study to investigate whether the presence of ANCA was associated with silica or any other form of occupational exposure, regardless of the underlying disease. All consecutive ANCA-positive patients recorded at the institution's Laboratory of Immunology between 1990 and 2000 were included. Patients hospitalized in a unit of internal medicine matched for age and gender were selected as controls (two controls/case). Qualitative and semiquantitative professional exposure and smoking habits were analyzed by five experts blind to the diagnosis. Univariate analysis showed that patients who reported dust exposure had a 2.6 greater risk of being ANCA-positive (P= 0.007) (odds ratio 2.6; 95% CI 1.3 to 5.3) and individuals with professional exposure to silica had a 3.4 higher risk of being ANCA-positive (P= 0.03) (odds ratio 3.4; 95% CI 1.1 to 9.9). None of the other environmental factors or smoking habits were different between ANCA-positive patients and controls. There was no difference in silica exposure between patients with cytoplasmic ANCA (c-ANCA), perinuclear ANCA (p-ANCA), or atypical ANCA. Semiquantitative analysis showed a dose effect of silica exposure with a nearly sevenfold greater risk of being ANCA-positive compared to controls (P= 0.02) (odds ratio 6.9; 95% CI 1.3 to 35.1). These results support the hypothesis that the presence of ANCA in plasma might at least partially be related to occupational exposure.

Selective killing of B-cell hybridomas targeting proteinase 3, Wegener's autoantigen.

Wegener's granulomatosis (WG) is a rare disease characterized by granulomatous lesions, small vessel vasculitis and the presence of anti-neutrophil cytoplasmic autoantibodies (C-ANCAs) in the sera of affected patients. Their main target antigen is proteinase 3 (PR3), a neutrophil and monocyte-derived neutral serine protease. Since the standard treatment of this severe autoimmune disease, with cyclophosphamide and corticosteroids, is associated with potential side-effects, the development of a more specific immunotherapeutic agent is warranted. The key role of ANCA in the pathogenesis of vasculitis and the effectiveness of anti-CD20 antibodies in patients with refractory WG points towards the importance of B cells in WG. We thus evaluated a new approach to selectively eliminate PR3-specific autoreactive B cells by targeting the B-cell receptor. For this purpose we used a bifunctional recombinant fusion protein consisting of the antigen PR3 and a toxin. The cytotoxic component of this novel fusion protein was the ribonuclease angiogenin, a human toxin with low immunogenicity. The toxin was stabilized by exchanging the catalytically relevant histidine in position 44 with glutamine to eliminate the autoproteolytic activity. PR3H44Q was fused either to the N terminus or to the C terminus of angiogenin. The recombinant proteins were expressed in 293T cells. Binding assays demonstrated the appropriate size and recognition by anti-PR3 antibodies. Using TUNEL technology, we demonstrated that these autoantigen toxins kill proteinase 3-specific B-cell hybridomas selectively by inducing apoptosis. The data indicate that autoantigen-toxins are promising tools in the treatment or co-treatment of autoimmune diseases in which the antigen is known.

Recurrence of ANCA-positive glomerulonephritis immediately after renal transplantation

Recurrence of crescentic necrotizing glomerulonephritis after renal transplantation is rare. Successful renal transplantation in patients with antineutrophil cytoplasmic autoantibody (ANCA) glomerulonephritis has been reported. The presence of ANCA at transplantation does not appear to increase the rate of relapse after kidney allografting. Therapy with cyclophosphamide and corticoids usually is effective. We report a case of recurrent perinuclear ANCA crescentic necrotizing glomerulonephritis immediately after renal transplantation that was treated successfully by cyclophosphamide, plasma exchange, and intravenous polyvalent immunoglobulin.

Recombinant Protein to Analyze Autoantibodies to Proteinase 3 in Systemic Vasculitis

The presence of antineutrophil cytoplasmic autoantibodies with specificity for proteinase 3 (PR3-ANCA) usually is detected by enzyme-linked immunosorbent assay (ELISA) with purified PR3 as a substrate. We studied the technical performance of direct and capture ELISA using a recombinant proteolytically inactive form of PR3 produced in the baculovirus expression system for the detection of PR3-ANCA in 114 patients with systemic vasculitis at diagnosis. We found that ELISA using recombinant PR3 produced in insect cells is a promising alternative for ELISA with native PR3. We found a correlation between tests using recombinant or native PR3, as well as correlation of the ELISA results with ANCA titers measured by the indirect immunofluorescence technique. However, the specificity for ANCA-associated vasculitis of ELISA with recombinant PR3 was lower than ELISA using native PR3. Compared with the direct assay, capture ELISA is a more sensitive method for PR3-ANCA detection, with both native and recombinant PR3, and its results depend on the monoclonal antibody used to capture the antigen.

Prevalence of antineutrophil cytoplasmic autoantibodies in patients with tuberculosis

To determine the prevalence of antineutrophil cytoplasmic autoantibodies (ANCA) in sera of patients with tuberculosis compared with healthy control subjects and a group of patients with atopic asthma. The presence of ANCA was examined in patients with tuberculosis, and in asthmatic patients and healthy subjects as control groups, by means of indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assay (ELISA) to detect anti-proteinase 3 (PR3-ANCA) and antimyeloperoxidase (MPO-ANCA) antibodies. ANCA were present in 20 (44.4%) of 45 tuberculosis patients by IIF (16 c-ANCA, four p-ANCA) and in 18 (40%) patients by ELISA (15 PR3-ANCA, three MPO-ANCA). High odds ratios for ANCA positivity were observed for tuberculosis patients when compared with both control groups. ANCA results were not related to the category of tuberculosis, stage of disease, presence of concomitant diseases or pharmacotherapy. As many clinical similarities between tuberculosis and Wegener's granulomatosis exist, we propose that a positive ANCA test in patients living in countries with a high prevalence of tuberculosis must be carefully interpreted as indicative of systemic vasculitis, especially when no signs of extrapulmonary involvement occur.

Proteinase 3 gene polymorphisms and Wegener's granulomatosis

Wegener's granulomatosis (WG) is a rare systemic autoimmune disease characterized by small-vessel vasculitis leading to organ damage and the presence of antineutrophil cytoplasmic autoantibodies (ANCAs). ANCAs were shown to be involved in the pathogenesis of the disease by increasing adhesion of polymorphonuclear cells (PMNs) to endothelial cells and through activation of primed PMN. The main autoantigen of ANCA in WG is proteinase 3 (PR3), a neutrophil- and monocyte-derived neutral serine protease. The association of WG with individuals continuously expressing a high level of PR3 on the surface of PMNs suggests that PR3 variants or altered regulation of PR3 expression might be directly involved in the pathogenesis of the disease. We screened the entire coding and promoter sequences of the PR3 gene for polymorphisms by means of polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP). Allelic, genotypic, and haplotype frequencies were compared between 79 WG patients and a cohort of 129 healthy controls. Seven single-nucleotide polymorphisms (SNPs), one amino acid change (Val119Ile), one 84 bp insertion/deletion, and a microsatellite were identified. An association with WG could be demonstrated for the A-564G polymorphism in the PR3 promoter affecting a putative transcription factor-binding site. This study excludes certain PR3 epitope variants as autoantigenic stimuli in WG, since the Val119Ile polymorphism showed no differences between patients and controls. Overexpression of PR3, however, might predispose the patient to the development of autoimmune ANCA-associated vasculitis.

Alpha1-antitrypsin phenotypes and anti-neutrophil cytoplasmic auto-antibodies in inflammatory bowel disease.

Alpha1-antitrypsin (alpha1-AT) is encoded by a highly polymorphic gene with over 75 codominantly expressed alleles at the protease inhibitor (Pi) locus classified as normal, deficient, dysfunctional or null. The aim of this study was to determine in patients with inflammatory bowel disease: (i) the prevalence of anti-neutrophil cytoplasmic auto-antibodies (ANCA) and their antigen specificities; (ii) alpha1-AT Pi phenotypes; and (iii) possible associations between ANCA, disease activity and deficient alpha1-AT alleles. Study of 95 consecutive patients with ulcerative colitis (UC) and 63 patients with Crohn's disease (CD). Diagnosis and disease activity were determined by clinical, endoscopic and histological criteria. ANCA by indirect immunofluorescence (IIF) and Pi phenotyping by isoelectric focusing were performed for all patients. Positive IIF sera were tested in antigen-specific enzyme-linked immunosorbent assay: proteinase 3 (PR3), myeloperoxidase (MPO), lactoferrin (LF), lysozyme, human leucocyte elastase (HLE), cathepsin G and bactericidal/permeability increasing protein (BPI). Sixty-one patients with UC (64.2%) and only 11 with CD (17.5%) had ANCA (P < 0.001). Antigen specificities were PR3 (7/61), MPO (3/61), LF (6/61), HLE (1/63) and BPI (10/61) in UC, and PR3 (2/11) and BPI (2/11) in CD. Three PiZ alleles were found, matching the prevalence in the normal French control population. No relationship was found between the presence of ANCA, antibody specificity, disease activity and deficient alpha1-AT alleles. ANCA are more frequent in UC than CD and do not correlate with disease activity. ANCA and protease/antiprotease imbalance do not appear to modulate the clinical course of inflammatory bowel disease.

Antineutrophil cytoplasmic antibodies in primary sclerosing cholangitis: defined specificities may be associated with distinct clinical features

PURPOSE: The clinical significance of antineutrophil cytoplasmic autoantibodies (ANCA) in primary sclerosing cholangitis has not been established. We investigated whether analysis of the antigenic specificities of ANCA is useful for delineating clinical subsets of the disease. METHODS: Sixty-nine patients with primary sclerosing cholangitis were studied. The presence of ANCA was analyzed by indirect immunofluorescence. Antibodies directed against specific antigens—proteinase 3, myeloperoxidase, elastase, bactericidal/permeability-increasing protein, cathepsin G, and lactoferrin—were identified by enzyme-linked immunosorbent assay. RESULTS: ANCA were detected by indirect immunofluorescence in 46 (67%) patients. In antigen-specific enzyme-linked immunosorbent assays, 37 (55%) of the 69 patients had antibodies to one or more antigens: 32 (46%) had antibodies to bactericidal/permeability-increasing protein, 16 (23%) had antibodies to cathepsin G, and 15 (22%) had antibodies to lactoferrin. Only 3 patients had antibodies to proteinase 3. Antibodies to myeloperoxidase or elastase were not detected. Twenty (29%) patients had antibodies to different antigens simultaneously. ANCA as detected by indirect immunofluorescence were not significantly associated with the presence of cirrhosis nor with the coexistence of inflammatory bowel disease. However, antibodies to bactericidal/permeability-increasing protein and cathepsin G were both associated with the presence of cirrhosis, and antibodies to lactoferrin were more frequently detected in patients with primary sclerosing cholangitis in conjunction with ulcerative colitis than in those without inflammatory bowel disease. CONCLUSION: Defined specificities of ANCA in primary sclerosing cholangitis may be related to particular clinical features of the disease.

Presence of antineutrophil cytoplasmic autoantibodies in patients with systemic lupus erythematosus

Presence of antineutrophil cytoplasmic autoantibodies in patients with systemic lupus erythematosus

Presence of antineutrophil cytoplasmic autoantibodies in patients with systemic lupus erythematosus

Presence of antineutrophil cytoplasmic autoantibodies in patients with systemic lupus erythematosus