Antineutrophil Cytoplasmic Autoantibodies Research Articles

Combination Therapy With Rituximab and Cyclophosphamide for Remission Induction in ANCA Vasculitis

IntroductionRemission induction in antineutrophil cytoplasmic autoantibody (ANCA) vasculitis may be complicated by slow response to treatment and toxicity from glucocorticoids. We describe outcomes with a novel remission induction regimen combining rituximab with a short course of low-dose, oral cyclophosphamide and an accelerated prednisone taper.MethodsPatients were included in this retrospective study if they had newly diagnosed or relapsing ANCA vasculitis with a Birmingham Vasculitis Activity Score for Wegener Granulomatosis (BVAS-WG) ≥3 and received a standardized remission induction regimen. The primary outcome was complete remission, defined as a BVAS-WG of 0 and a prednisone dose of ≤7.5 mg/d.ResultsWe identified 129 patients who met the inclusion criteria, 31% of whom also received plasma exchange (PLEX) for rapidly progressive glomerulonephritis (RPGN) or diffuse alveolar hemorrhage. Seventy percent of patients had myeloperoxidase (MPO)-ANCA and 9% had relapsing disease. Median time to complete remission was 4 months (interquartile range [IQR] 3.9–4.4), and by 5 months 84% of patients were in complete remission. Prednisone was tapered to discontinuation as tolerated, such that the median prednisone dose at 8 months was 0 mg/d (IQR 0–2.5). In patients with RPGN, proteinase 3–ANCA was associated with a greater increase in eGFR at 6 months compared with MPO-ANCA (16 vs. 5.6 ml/min per 1.73m2; P = 0.028). During the year following remission, 1 major relapse occurred over 122 patient-years. Serious infections occurred more frequently in patients receiving PLEX and were associated with increasing age and diffuse alveolar hemorrhage. Four deaths occurred, 3 of which were associated with serious infections.ConclusionCombination therapy was efficacious, allowed for rapid tapering of high-dose glucocorticoids and was well tolerated.

The Epidemiology of Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis in Olmsted County, Minnesota: A Twenty-Year US Population-Based Study.

To estimate the annual incidence, prevalence, and mortality of antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) and its subsets, granulomatosis with polyangiitis (Wegener's) (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (EGPA), in a US-based adult population. All medical records of patients with a diagnosis of, or suspicion of having, AAV in Olmsted County, Minnesota from January 1, 1996 to December 31, 2015 were reviewed. AAV incidence rates were age- and sex-adjusted to the 2010 US white population. Age- and sex-adjusted prevalence of AAV was calculated on January 1, 2015. Survival rates observed in the study cohort were compared with expected rates in the Minnesota population. Of the 58 incident cases of AAV in Olmsted County during the study period, 23 (40%) were cases of GPA, 28 (48%) were cases of MPA, and 7 (12%) were cases of EGPA. Overall, 28 (48%) of the patients with AAV were women and 57 (98%) were white. The mean ± SD age at diagnosis was 61.1 ± 16.5 years. Thirty-four patients (61%) had myeloperoxidase (MPO)-ANCAs, and 17 (30%) were positive for proteinase 3 (PR3)-ANCAs; 5 (9%) were ANCA-negative. The annual incidence of AAV was 3.3 per 100,000 population (95% confidence interval [95% CI] 2.4-4.1). The incidence rates of GPA, MPA, and EGPA were 1.3 (95% CI 0.8-1.8), 1.6 (95% CI 1.0-2.2), and 0.4 (95% CI 0.1-0.6), respectively. The overall prevalence of AAV was 42.1 per 100,000 (95% CI 29.6-54.6). The mortality rate among AAV patients overall, and among patients with EGPA, those with MPA, and those with MPO-ANCAs, was increased in comparison to the Minnesota general population (each P < 0.05), whereas mortality rates among patients with GPA, those with PR3-ANCAs, and ANCA-negative patients did not differ from that in the general population. The annual incidence of AAV in Olmsted County, Minnesota over the 20 years of the study was 3.3 per 100,000, with a prevalence of 42.1 per 100,000, which is substantially higher than the rates reported in other areas worldwide. The incidence of GPA was similar to that of MPA. Patients with MPA and those with EGPA, but not patients with GPA, experienced higher rates of mortality than that in the Minnesota general population. MPO-ANCAs were a marker of poor survival in this population of patients with AAV.

Alterations in circulating lymphoid cell populations in systemic small vessel vasculitis are non-specific manifestations of renal injury.

Innate lymphocyte populations, such as innate lymphoid cells (ILCs), γδ T cells, invariant natural killer T (iNK T) cells and mucosal-associated invariant T (MAIT) cells are emerging as important effectors of innate immunity and are involved in various inflammatory and autoimmune diseases. The aim of this study was to assess the frequencies and absolute numbers of innate lymphocytes as well as conventional lymphocytes and monocytes in peripheral blood from a cohort of anti-neutrophil cytoplasm autoantibody (ANCA)-associated vasculitis (AAV) patients. Thirty-eight AAV patients and 24 healthy and disease controls were included in the study. Patients with AAV were sampled both with and without immunosuppressive treatment, and in the setting of both active disease and remission. The frequencies of MAIT and ILC2 cells were significantly lower in patients with AAV and in the disease control group compared to healthy controls. These reductions in the AAV patients remained during remission. B cell count and frequencies were significantly lower in AAV in remission compared to patients with active disease and disease controls. Despite the strong T helper type 2 (Th) preponderance of eosinophilic granulomatosis with polyangiitis, we did not observe increased ILC2 frequency in this cohort of patients. The frequencies of other cell types were similar in all groups studied. Reductions in circulating ILC2 and MAIT cells reported previously in patients with AAV are not specific for AAV, but are more likely to be due to non-specific manifestations of renal impairment and chronic illness. Reduction in B cell numbers in AAV patients experiencing remission is probably therapy-related.

An Atypical Cause of Hemoptysis

SESSION TITLE: Fungal Infections 1 SESSION TYPE: Affiliate Case Report Poster PRESENTED ON: Tuesday, October 31, 2017 at 01:30 PM - 02:30 PM INTRODUCTION: Cryptococcus presenting as an endobronchial mass lesion is rare. We present an unusual case of pulmonary cryptococcosis in an immunocompetent patient encountered in clinical practice. CASE PRESENTATION: Patient is a 48y/o AAF with a past medical history notable for cough variant asthma, and hypertension. She had a persistent cough for many years. Initial imaging performed for work-up of her chronic cough was unremarkable. Full pulmonary function test were normal. Ig E levels were elevated at 255 kU/L with immunocap testing revealing high levels of reactivity to dust mites, animal dander and grasses. The patient was managed with formoterol/ mometasone and an albuterol rescue inhaler as needed with variable compliance. She presented for re-evaluation after she noted a change in her cough for several months. Her cough had initially been dry but had become productive a small amount of blood tinged sputum. She was seen in the emergency department shortly after the onset of hemoptysis and was told that she had pneumonia. She was discharged on a 7 day course of levofloxacin without a significant improvement in her symptoms. CT scan of the chest performed 3 months after the onset of symptoms showed a right lower lobe mass like consolidation (Figure 1). The patient continued to experience a chronic cough with intermittent hemoptysis, describing it as “puddles of blood in my phlegm” more frequently in the morning. At that time, she also complained of worsening dyspnea with exertion, polyarthralgias and fatigue. Antinuclear antibody, antineutrophil cytoplasmic autoantibodies and rheumatoid factor were negative. Fiberoptic bronchoscopy revealed an endobronchial mass obstructing the one of the right lower lobe medial basilar subsegments. Bronchoalveolar lavage demonstrated budding yeasts, positive fungal stains and endobronchial biopsy of the mass had innumerable intracellular yeast forms with a clear capsule suggestive of Cryptococcus (figure 2). Patient was started on itraconazole. DISCUSSION: The clinical presentation of Cryptococcus is highly variable and often related to the burden of exposure, virulence factor or quality of immune response[1]. In the immunocompetent host primary infection is usually asymptomatic. These patients are usually identified incidentally by abnormal chest imaging or on biopsy of a lung mass or on cultures of lung specimens obtained for other reasons[2,3]. Cough is the most common pulmonary symptom if the patient is symptomatic. CONCLUSIONS: Pulmonary cryptococcosis has a wide range of presentations and should be considered as a cause of chronic cough even in immunocompetent patients. Reference #1: Jarvis JN1, Harrison TS. Pulmonary cryptococcosis. Semin Respir Crit Care Med. 2008 Apr;29(2):141-50. doi: 10.1055/s-2008-1063853. Reference #2: Lindell RM1, Hartman TE, Nadrous HF, Ryu JH. Pulmonary cryptococcosis: CT findings in immunocompetent patients. Radiology. 2005 Jul;236(1):326-31. DISCLOSURE: The following authors have nothing to disclose: Valentina Amaral, Kala Davis-McDonald No Product/Research Disclosure Information

Sniffles, Hemoptysis, and Headache That Just Would Not Go Away

SESSION TITLE: Pulmonary Manifestations of Systemic Disease 4 SESSION TYPE: Affiliate Case Report Poster PRESENTED ON: Tuesday, October 31, 2017 at 01:30 PM - 02:30 PM INTRODUCTION: Granulomatosis with polyangiitis (GPA), previously recognized as Wegener’s granulomatosis, is part of group of antineutrophil cytoplasmic autoantibody (ANCA) associated vasculitides (AAV). Some of the clinical criteria for diagnosis include: nasal, or oral inflammation, chest radiographs with the presence of nodules/infiltrates, abnormal urinary sedimentation with microscopic hematuria, and lastly granulomatous inflammation on biopsy of an affected artery. CASE PRESENTATION: A 63 year old hispanic female with a past medical history of hypertension, type II diabetes mellitus who presented for a 3 month history of left sided facial droop, and headache. Patient reported that headache was initially holofrontal, but progressed to include left ear, and subsequent blurry vision. Patient was prescribed cefdinir, and prednisone taper for presumed infection. Patient had associated dysphagia, 20 pound weight loss, low grade fevers, night sweats, intermittent episodes of hemoptysis, and persistent vaginal bleeding for the preceding 2 weeks. On exam, she was afebrile and HEENT exam was significant for left sided facial droop, poor dentition, and cervical lymphadenopathy. Gynecology noted patient to have large cervical mass. Patient started on broad spectrum intravenous antibiotics. CT head/sinus/neck/chest were remarkable for 1 cm intra-axial lesion in right putamen, chronic right maxillary sinusitis, with prominent lymph nodes within anterior cervical, mediastinal regions, left parotid abscess, and multiple spiculated cavitary/noncavitary lung lesions. 2D echocardiogram had no vegetations. Erythrocyte sedimentation rate was 94 and C-reactive protein was elevated 26.87. Patient was started on oral prednisone taper, and antibiotics for Bell’s palsy, and parotiditis. Patient received lumbar puncture with cerebral spinal fluid pleocytosis. Bronchoscopy noted fungating mass with necrotic base, and negative cultures. Cervical mass biopsy noted necrotic cells with no mention of malignancy. Autoantibody to proteinase-3 (PR-3 (c-ANCA)) level was 17.4 (reference range <0.1). Urinalysis was significant for proteinuria, hematuria, and glycosuria. Patient was started on high dose methylprednisone, and plasmapheresis with slight improvement in Bell’s palsy, and systemic symptoms. DISCUSSION: Positive C-ANCA is detected in > 85% of patients with active disease. GPA generally presents in older Caucasian adults (40-65 years old) with no gender predominance. If left untreated GPA has a poor prognosis with up to 90% mortality rate. CONCLUSIONS: GPA has been seldom described in literature with symptom presentation including: progressive ipsilateral peripheral facial nerve paralysis, parotiditis, mononeuritis multiplex, cervical granulomas, hemoptysis, along with progressive kidney injury. Reference #1: Falk RJ, Gross WL, Guillevin L, et al. Granulomatosis with polyangiitis (Wegener's): an alternative name for Wegener's granulomatosis. Ann Rheum Dis. 2011;70(4):704. DISCLOSURE: The following authors have nothing to disclose: Emmanuel Bassily, Daniel Mathew, Vindya Gunawardena, Jibran Khan, Sean Verma, Chak Sriaroon No Product/Research Disclosure Information

Genetic loci of Staphylococcus aureus associated with anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides

The proteinase 3 (PR3)-positive anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) granulomatosis with polyangiitis (GPA) has been associated with chronic nasal S. aureus carriage, which is a risk factor for disease relapse. The present study was aimed at comparing the genetic make-up of S. aureus isolates from PR3-ANCA-positive GPA patients with that of isolates from patients suffering from myeloperoxidase (MPO)-ANCA-positive AAV, and isolates from healthy controls. Based on a DNA microarray-based approach, we show that not only PR3-ANCA-positive GPA patients, but also MPO-ANCA-positive AAV patients mainly carried S. aureus types that are prevalent in the general population. Nonetheless, our data suggests that MPO-ANCA-associated S. aureus isolates may be distinct from healthy control- and PR3-ANCA-associated isolates. Furthermore, several genetic loci of S. aureus are associated with either PR3-ANCA- or MPO-ANCA-positive AAV, indicating a possible role for pore-forming toxins, such as leukocidins, in PR3-ANCA-positive GPA. Contrary to previous studies, no association between AAV and superantigens was detected. Our findings also show that a lowered humoral immune response to S. aureus is common for PR3-ANCA- and MPO-ANCA-positive AAV. Altogether, our observations imply that the presence or absence of particular virulence genes of S. aureus isolates from AAV patients contributes to disease progression and/or relapse.

Changes in CD73, CD39 and CD26 expression on T-lymphocytes of ANCA-associated vasculitis patients suggest impairment in adenosine generation and turn-over

Extracellular adenosine, generated via the concerted action of CD39 and CD73, contributes to T-cell differentiation and function. Adenosine concentrations are furthermore influenced by adenosine deaminase binding protein CD26. Because aberrant T-cell phenotypes had been reported in anti-neutrophil cytoplasmic auto-antibody (ANCA)-associated vasculitis (AAV) patients, an impaired expression of these molecules on T-cells of AAV patients was hypothesized in the present study. While in AAV patients (n = 29) CD26 was increased on CD4+ lymphocytes, CD39 and CD73 were generally reduced on patients’ T-cells. In CD4+ cells significant differences in CD73 expression were confined to memory CD45RA- cells, while in CD4- lymphocytes differences were significant in both naïve CD45RA+ and memory CD45RA- cells. The percentage of CD4-CD73+ cells correlated with micro-RNA (miR)−31 expression, a putative regulator of factor inhibiting hypoxia-inducible factor 1 alpha (FIH-1), inversely with serum C-reactive protein (CRP) and positively with estimated glomerular filtration rate (eGFR). No correlation with disease activity, duration, and ANCA profile was found. It remains to be assessed if a decreased CD73 and CD39 expression underlies functional impairment of lymphocytes in AAV patients. Likewise, the relations between frequencies of CD4-CD73+ cells and serum CRP or eGFR require further functional elucidation.

Autoimmune Thyroiditis and Glomerulopathies.

Autoimmune thyroiditis (AIT) is generally associated with hypothyroidism. It affects ~2% of the female population and 0.2% of the male population. The evidence of thyroid function- and thyroid autoantibody-unrelated microproteinuria in almost half of patients with AIT and sometimes heavy proteinuria as in the nephrotic syndrome point to a link of AIT with renal disease. The most common renal diseases observed in AIT are membranous nephropathy, membranoproliferative glomerulonephritis, minimal change disease, IgA nephropathy, focal segmental glomerulosclerosis, antineutrophil cytoplasmic autoantibody (ANCA) vasculitis, and amyloidosis. Different hypotheses have been put forward regarding the relationship between AIT and glomerulopathies, and several potential mechanisms for this association have been considered. Glomerular deposition of immunocomplexes of thyroglobulin and autoantibodies as well as the impaired immune tolerance for megalin (a thyrotropin-regulated glycoprotein expressed on thyroid cells) are the most probable mechanisms. Cross-reactivity between antigens in the setting of genetic predisposition has been considered as a potential mechanism that links the described association between ANCA vasculitis and AIT.

Vascular Diseases of the Kidney

A number of local and systemic disease processes affect the renal vascular tree. Although the underlying mechanisms may differ, vascular diseases of the kidney all characteristically cause varying degrees of vessel obstruction, eventually leading to an impairment of renal blood flow. Acute impairment in renal function occurs in most vascular diseases of the kidney. This chapter discusses the major vascular diseases of the kidney, categorized according to the size of the affected vessel. Large-vessel diseases described are renal artery stenosis from atherosclerosis and fibromuscular dysplasia, Takayasu arteritis, and renal vein thrombosis. Medium-size-vessel diseases described are polyarteritis nodosa and Kawasaki disease. Small-vessel diseases described are those traditionally associated with glomerulopathy, including rapidly progressive glomerulonephritis and Henoch-Schönlein purpura; thrombotic microangiopathy, including thrombotic thrombocytopenic purpura, hemolytic-uremic syndrome, preeclampsia, antiphospholipid syndrome, systemic sclerosis, and malignant hypertension; sickle cell disease; and atheroembolic disease. Tables describe the American College of Rheumatology classification criteria for Takayasu arteritis and induction therapy for rapidly progressive glomerulonephritis. Figures show an overview of vascular disease of the kidney; an arteriogram of renal artery stenosis demonstrating an ostial lesion; light microscopy showing typical crescentic glomerulonephritis; purpuric eruptions in small vessel vasculitides, Henoch-Schönlein purpura, hypersensitivity vasculitis, and antineutrophil cytoplasmic autoantibody–associated disease; light microscopy showing the characteristic onion-skin lesion in scleroderma renal crisis; electron microscopy showing a glomerular capillary with thrombotic thrombocytopenic purpura; injection microradioangiograms comparing the vasa recta of a normal kidney with that in a patient with sickle cell disease; and a light microscopy that reveals an atheroembolus lodged in a small renal artery and occlusion of the vascular lumen. This chapter contains 151 references.

Vascular Diseases of the Kidney

A number of local and systemic disease processes affect the renal vascular tree. Although the underlying mechanisms may differ, vascular diseases of the kidney all characteristically cause varying degrees of vessel obstruction, eventually leading to an impairment of renal blood flow. Acute impairment in renal function occurs in most vascular diseases of the kidney. This chapter discusses the major vascular diseases of the kidney, categorized according to the size of the affected vessel. Large-vessel diseases described are renal artery stenosis from atherosclerosis and fibromuscular dysplasia, Takayasu arteritis, and renal vein thrombosis. Medium-size-vessel diseases described are polyarteritis nodosa and Kawasaki disease. Small-vessel diseases described are those traditionally associated with glomerulopathy, including rapidly progressive glomerulonephritis and Henoch-Schönlein purpura; thrombotic microangiopathy, including thrombotic thrombocytopenic purpura, hemolytic-uremic syndrome, preeclampsia, antiphospholipid syndrome, systemic sclerosis, and malignant hypertension; sickle cell disease; and atheroembolic disease. Tables describe the American College of Rheumatology classification criteria for Takayasu arteritis and induction therapy for rapidly progressive glomerulonephritis. Figures show an overview of vascular disease of the kidney; an arteriogram of renal artery stenosis demonstrating an ostial lesion; light microscopy showing typical crescentic glomerulonephritis; purpuric eruptions in small vessel vasculitides, Henoch-Schönlein purpura, hypersensitivity vasculitis, and antineutrophil cytoplasmic autoantibody–associated disease; light microscopy showing the characteristic onion-skin lesion in scleroderma renal crisis; electron microscopy showing a glomerular capillary with thrombotic thrombocytopenic purpura; injection microradioangiograms comparing the vasa recta of a normal kidney with that in a patient with sickle cell disease; and a light microscopy that reveals an atheroembolus lodged in a small renal artery and occlusion of the vascular lumen. This chapter contains 151 references.

Identification of Functional and Expression Polymorphisms Associated With Risk for Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis.

ObjectiveTo identify risk alleles relevant to the causal and biologic mechanisms of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV).MethodsA genome‐wide association study and subsequent replication study were conducted in a total cohort of 1,986 cases of AAV (patients with granulomatosis with polyangiitis [Wegener's] [GPA] or microscopic polyangiitis [MPA]) and 4,723 healthy controls. Meta‐analysis of these data sets and functional annotation of identified risk loci were performed, and candidate disease variants with unknown functional effects were investigated for their impact on gene expression and/or protein function.ResultsAmong the genome‐wide significant associations identified, the largest effect on risk of AAV came from the single‐nucleotide polymorphism variants rs141530233 and rs1042169 at the HLA–DPB1 locus (odds ratio [OR] 2.99 and OR 2.82, respectively) which, together with a third variant, rs386699872, constitute a triallelic risk haplotype associated with reduced expression of the HLA–DPB1 gene and HLA–DP protein in B cells and monocytes and with increased frequency of complementary proteinase 3 (PR3)–reactive T cells relative to that in carriers of the protective haplotype. Significant associations were also observed at the SERPINA1 and PTPN22 loci, the peak signals arising from functionally relevant missense variants, and at PRTN3, in which the top‐scoring variant correlated with increased PRTN3 expression in neutrophils. Effects of individual loci on AAV risk differed between patients with GPA and those with MPA or between patients with PR3‐ANCAs and those with myeloperoxidase‐ANCAs, but the collective population attributable fraction for these variants was substantive, at 77%.ConclusionThis study reveals the association of susceptibility to GPA and MPA with functional gene variants that explain much of the genetic etiology of AAV, could influence and possibly be predictors of the clinical presentation, and appear to alter immune cell proteins and responses likely to be key factors in the pathogenesis of AAV.

Th17 and Treg lymphocytes as cellular biomarkers of disease activity in Granulomatosis with Polyangiitis.

Granulomatosis with Polyangiitis (GPA) (formerly known as Wegener's granulomatosis) is a vasculitis of unknown etiology affecting predominantly small- to medium-sized vessels, usually involving the upper and lower respiratory tract and kidneys. Anti-neutrophil cytoplasmic autoantibodies are probably the initial cause of the inflammatory process that leads to the typical necrotizing lesions. In this issue of the European Journal of Immunology, Szczeklik etal. [Eur. J. Immunol. 2017. 47: 724-733] report some interesting findings on the possible involvement of T-cell subsets in the pathogenesis of the disease. This prospective study, performed on a large cohort of patients, identifies Th17 lymphocytes as the possible pathogenic subset of GPA, and Treg cells as the possible suppressors of the inflammatory process. These two subsets in peripheral blood could be used as cellular biomarkers of disease activity, and this would result particularly useful in the follow-up of patients once the immunosuppressive treatment has been initiated.

Onset of Microscopic Polyangiitis in Binephrectomied Patient on Chronic Hemodialysis-Case Report.

Microscopic polyangiitis (MPA) is one of the causes of the pulmonary-renal syndrome associated with elevated non-specific markers of inflammation and antineutrophil cytoplasmic autoantibody (ANCA) positivity in 50-75%. De novo occurrence of the disease in patients on chronic hemodialysis (HD) has not been described. We presented patient who developed MPO-ANCA-associated MPA with lung and musculoskeletal involvement after 4 years on regular HD due to bilateral nephrectomy. After excluding the other causes of MPO-ANCA positivity, diagnosis was confirmed even without renal biopsy. Patient received standard immunosuppression therapy and he is still in remission after 27 months. The onset of immune-mediated disease could be observed even after introduction of renal replacement therapy, which may be a diagnostic problem. Early recognition and traditional immunosuppressive regiment may provide successful outcome.

Neutrophil extracellular traps in neuropathy with anti-neutrophil cytoplasmic autoantibody-associated microscopic polyangiitis

To clarify the roles of neutrophils in anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitic neuropathy, we studied neutrophil extracellular traps (NETs) in peripheral nerve vasculitis. Stored nerve samples from 17 patients with microscopic polyangiitis (MPA) were immunohistochemically analyzed using antibodies for citrullinated histone H3 (citH3) and various neutrophil enzymes. We defined merged citH3 and extracellularly released myeloperoxidase (MPO) as NET formation. We also compared NET formation between MPO-ANCA-positive/negative MPA and rheumatoid arthritis (RA)-associated vasculitic neuropathy. NETs were identified mostly in vasculitic small arterioles of 6 of 12 MPO-ANCA-positive MPA patients, and their frequency was higher (p<0.05) than in ANCA-negative patients. NETs were not found in vasculitic neuropathy with RA or patients with chronic inflammatory demyelinating polyradiculoneuropathy. NETs were also observed in the peripheral nervous system of MPA patients as well as in the lung and kidney. These results suggest that NETs may be involved in the pathogenesis of MPA neuropathy.

Granulomatose mit Polyangiitis

Granulomatosis with polyangiitis (GPA) is a potentially life-threatening, rare disease. The etiology is unknown. GPA is histomorphologically characterized by extravascular necrotizing granulomatous inflammation and a systemic necrotizing vasculitis of small to medium-sized vessels. Clinically, a pulmonary-renal syndrome with pulmonary infiltrates, alveolar hemorrhage and a rapidly progressive glomerulonephritis is seen in about 80% of the cases with generalized disease. GPA is associated with proteinase 3-specific anti-neutrophil cytoplasmic autoantibodies (PR3-ANCA). Treatment is guided by severity of organ involvement and disease activity. Cytostatic immunosuppressants or the monoclonal anti-CD20 antibody rituximab are applied.

The Effects of Plasma Exchange on Severe Vasculitis with Diffuse Alveolar Hemorrhage

Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis is a life-threatening disease characterized by rapidly progressive glomerulonephritis (RPGN) and diffuse alveolar hemorrhage (DAH). Glucocorticoids and immunosuppressants are commonly used to treat this disease but may induce irreversible side effects, particularly in elderly patients. We herein report the case of a 76-year-old woman with RPGN. After methylprednisolone pulse therapy, DAH occurred, and she required ventilatory support. After plasma exchange, her serum creatinine level improved, and she was discharged with home oxygen therapy. Immunosuppressive agents other than glucocorticoids were not required. In conclusion, plasma exchange with glucocorticoid therapy may be effective in treating severe ANCA-associated vasculitis in elderly patients.

The functional activities of complement factor H are impaired in patients with ANCA-positive vasculitis

Increasing evidences have demonstrated that the activation of the alternative complement pathway is crucial for the pathogenesis of anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). Our recent study found that circulating levels of complement factor H (FH), a key regulator of the alternative pathway, were associated with disease activity. In the current study, functional activities of FH were assessed to further explore the potential role of FH in the pathogenesis of AAV. We found that the two patients with ANCA-negative pauci-immune necrotizing crescentic glomerulonephritis exhibited relatively normal functional activities of FH. However, patients with ANCA-positive vasculitis exhibited deficient functional activities of FH, in terms of interaction with and the regulation of C3b, binding to mCRP and endothelial cells, and the protection of host cells against complement attack. Our findings indicate that functional activities of FH are deficient in patients with ANCA-positive vasculitis, potentially contributing to the disease development.

Cardiac manifestations in antineutrophil cytoplasmic autoantibody (ANCA) — associated vasculitides

Cardiac manifestations in antineutrophil cytoplasmic autoantibody (ANCA) — associated vasculitides

Pathogenesis and treatment of ANCA-associated vasculitis-a role for complement.

The antineutrophil cytoplasm autoantibody (ANCA)-associated vasculitides (AAV), although rare in childhood, can have devastating effects on affected organs, especially the kidney. In this review we present an update on the pathogenesis and treatment of ANCA vasculitis, with a particular emphasis on the role of the alternative pathway of complement. The rationale and evidence for the current treatment strategies are summarized. Targeting the activation of neutrophils by the anaphylatoxin C5a may serve as an additional therapeutic strategy, however the results of clinical studies are awaited.

Autoantibody profiles and their association with blood eosinophils in asthma and COPD

BackgroundAutoimmune involvement in the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD) has been proposed, and autoantibodies are a hallmark of autoimmunity. This study aimed to compare the autoantibody profiles of asthma and COPD, and the relationship between autoantibodies and features of these diseases. MethodsWe recruited 110 asthma patients and 92 COPD patients for a prospective study. Six autoantibody types were evaluated: antinuclear antibody, anti-cytoplasmic antibodies, rheumatoid factor, anti-cyclic citrullinated peptide antibody, myeloperoxidase–anti-neutrophil cytoplasmic autoantibody (MPO-ANCA) and proteinase 3-ANCA. Other clinical data were also recorded concurrently. ResultsAn antinuclear antibody titre of ≥1:160 presented only in asthma but not in COPD (10% vs. 0%, p = 0.0002). Eosinophil counts in blood were negative predictors of antinuclear antibody in asthma. Conversely, eosinophil counts in blood and immunoglobulin-E levels of ≥100 IU/mL were positively associated with rheumatoid factor in asthma but not in COPD. There was no relationship between antinuclear antibody or rheumatoid factor and disease severity. ConclusionsIt is possible that asthma tends to involve autoimmunity associated with antinuclear antibody more frequently than COPD because asthma is the more robust factor for antinuclear antibody positivity. Antinuclear antibody and rheumatoid factor are associated with eosinophilic responses, but they do not work as biomarkers for disease severity.