Autoantibody-associated Vasculitis Research Articles

An unusual form of kidney injury without glomerulonephritis in microscopic polyangiitis: a case report

BackgroundMicroscopic polyangiitis (MPA), a kind of antineutrophil cytoplasmic autoantibody associated vasculitis (AAV), predominantly affects small-sized vessels. MPA is a significant cause of the pulmonary-renal syndrome. Pauci-immune necrotizing and crescentic glomerulonephritis is the typical renal histological feature of AAV. Tubulointerstitial lesions may occur and mostly form with inflammatory cell infiltration in the interstitium. However, a few cases reported only tubulointerstitial involvement without glomerular lesions in patients with MPA.Case presentationWe present an MPA case, a 70-year-old male patient diagnosed with acute kidney injury accompanying the dialysis requirement. Only acute tubulointerstitial nephritis was revealed in kidney biopsy without evidence of glomerular injury. Also, interstitial pulmonary fibrosis was determined on computerized tomography, and myeloperoxidase antineutrophil cytoplasmic autoantibody was positive. Consequently, we have considered the main diagnosis as MPA. We did not prefer a standard tubulointerstitial nephritis treatment regimen due to the presence of life-threatening systemic vasculitis. Treatment was established like crescentic glomerulonephritis. Induction therapy consisted of pulse steroid, cyclophosphamide, and plasmapheresis. Unfortunately, severe SARS-CoV-2 infection caused death during induction therapy in this case.ConclusionsThe lack of glomerular injury and solely interstitial inflammation is atypical regarding AAV involvement in the kidney. This diversity might be initially considered as only a simple histological elaboration. However, it is a significant entity for guiding the treatment of AAV.

SARS-CoV-2 Vaccine Response in Patients With Antineutrophil Cytoplasmic Autoantibody–Associated Vasculitis

The development of COVID-19 vaccines and mass vaccination is a landmark achievement of modern medicine. Management of patients with antineutrophil cytoplasmic autoantibodies–associated vasculitis (AAV) during the pandemic has been challenging. Immunosuppressive medications to control vasculitis are associated with severe COVID-19 infection and may impair immune response to the vaccine.

A comparative analysis of different biofluids using Raman spectroscopy to determine disease activity in ANCA‐associated vasculitis

AbstractIdentifying persistent or relapsing disease in anti‐neutrophil cytoplasmic autoantibody‐ associated vasculitis (AAV) remains a clinical challenge with an unmet need for a reliable biomarker of multisystem disease. In this study, we confirm for the first time that Raman spectroscopy offers a novel cost‐effective candidate biomarker to discriminate active disease from remission in AAV with excellent accuracy. Spectrochemical interrogation of plasma and serum samples demonstrated equal ability to discriminate disease activity with good group separation on PC1 direction and a high degree of accuracy on validation testing using blind predictive modelling: F‐score 80% for plasma (specificity 93.3%, sensitivity 70%, AUC 0.95) and 80% for serum (specificity 80%, sensitivity 80%, AUC 0.92). Similar findings were seen on analysis of paired remission samples following successful remission‐induction therapy. A larger study with longitudinal data is required to validate these findings with the potential to aid patient care.

Clinical Use of Complement, Inflammation, and Fibrosis Biomarkers in Autoimmune Glomerulonephritis

IntroductionComplement activation, inflammation, and fibrosis play central roles in the mechanisms of injury in autoimmune glomerulonephritis (GN) but they are seldom assessed in epidemiologic studies. The measurement of urinary biomarkers of these pathways of injury could parallel disease activity and add clinical value beyond proteinuria.MethodsWe performed a prospective cohort study of 100 patients with focal and segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), IgA nephropathy (IgAN), lupus nephritis (LN), anti-neutrophil cytoplasmic autoantibody–associated vasculitis (AAV), and membranoproliferative GN (MPGN) followed for 33 (18–54) months. Repeated urinary samples were collected throughout their follow-up to determine proteinuria, urinary sC5b-9, monocyte chemoattractant protein–1 (MCP-1), and transforming growth factor–beta 1 (TGF-β1), expressed as creatinine ratios. We identified 177 periods of active and inactive disease based on current remission definitions for each disease.ResultsUrinary sC5b-9, MCP-1, and TGF-β1 were present in each disease. In periods leading to a remission, the reduction of urinary sC5b-9 was 91%, greater than for proteinuria with 76%. During inactive periods, those who did not experience a relapse maintained lower levels of biomarkers compared with those who relapsed. At that time, the increase in urinary sC5b-9 was significantly greater than the rise in proteinuria (8.5-fold increase compared with 3.2-fold) and urinary MCP-1 and TGF-β1. Using current remission definitions for each disease, thresholds for each biomarker were determined using receiver operating characteristic curves. Individuals who averaged levels below these cutoffs during their follow-up had better renal outcomes.ConclusionIn autoimmune glomerular diseases, urinary sC5b-9, MCP-1, and TGF-β1 are present and parallel disease activity and outcomes. Urinary sC5b-9 appears to be a more discerning marker of immunologic remissions and relapses.

Anti-neutrophil cytoplasmic autoantibodies associated vasculitis – Clinical profile and outcomes

Background: Studies on antineutrophil cytoplasmic autoantibodies-associated vasculitis (AAV) from India are scarce. The aim of the present study was to characterize the profile of AAV and experience with rituximab in ocular granulomatous with polyangiitis (GPA) in our cohort. Methods: Clinical, laboratory, and treatment details of AAV from January 2010 to May 2017 were noted. Continuous variables were reported as mean and standard deviation (SD). In GPA, clinical variables between survivors and nonsurvivors were compared using independent sample t -test and Fisher's exact test. Cox regression analysis was done to estimate the hazard ratios. Our cohort of GPA was compared with other large single-center cohorts from India, USA, Germany, and France. Results: Thirty-one patients were diagnosed to have AAV. Seventeen were females. GPA was most common phenotype (23/31). Mean (SD) age at onset was 39.8 (15.7) years. Median (IQ) time to diagnosis was 6 (22) months. The most common manifestations in GPA were ocular ( n = 20) and lower respiratory tract ( n = 13). Mean (SD) Birmingham Vasculitis Activity Score (BVAS) at disease onset was 9.4 (6.9). Pulse methylprednisolone with cyclophosphamide was used as induction regime followed by maintenance with azathioprine. Rituximab was given to four patients with refractory GPA. Six patients succumbed to illness. Remission was achieved in 19/25 survivors. Mean (SD) BVAS at disease onset was significantly higher in nonsurvivors (17.6 ± 10.2) compared to survivors (9.4 ± 4.9) ( P = 0.018). Higher proportion of renal involvement was seen in nonsurvivors ( P = 0.03). There was three-fold increased mortality with renal and lung involvement. In addition, the risk of death increases by 1.13 fold with each point increase in BVAS score. Conclusion: Ocular involvement was higher in our GPA cohort. Baseline BVAS, renal, and lung involvement predicts poor prognosis in GPA. Sustained remission with rituximab was seen in all patients with refractory ocular disease.

The elusive optimal induction strategy for vasculitis

A recently published study on therapy for antineutrophil cytoplasmic autoantibody-associated small vessel vasculitis has provided answers but not clarity towards defining how best to treat patients with vasculitis. How do we use recent advances in knowledge to optimally influence our patients' outcomes without causing harm in the process?

True vasculitis in lupus nephritis

Vascular lesions are encountered frequently in renal biopsy specimens of patients with systemic lupus erythematosus (SLE) and can present in a variety of morphologic forms. True renal lupus vasculitis (TRLV) is one of the rare vascular lesions associated with lupus nephritis that has been infrequently reported in the medical literature. The primary focus on glomerular pathology and collective classification of the vascular lesions under lupus vasculopathy is one of the reasons why this form of inflammatory vasculitis has been under-recognized as a separate disease entity. Here we have comprehensively reviewed the literature on renal vascular involvement in SLE for a better understanding of the epidemiology, morphologic features, pathogenesis, clinical course and treatment of TRLV. It can be morphologically differentiated from other forms of renal vascular lesions in lupus nephritis, i.e. arteriosclerosis, uncomplicated vascular immune deposits, non-inflammatory necrotizing vasculopathy, and thrombotic microangiopathy. Despite close similarities with antineutrophil cytoplasmic autoantibody associated vasculitis (AASV), there are certain morphological differences that warrant a thorough investigation of the possible pauci-immune mechanism of pathogenesis. The vasculitis follows a severe clinical course in general with rapid progression to renal failure, although favorable outcomes have been reported in certain cases. The standard use of steroids and cytotoxic drugs has yielded variable results in the treatment of TRLV. Current treatment modalities being used in lupus nephritis and AASV have been compared in this article with focus on drugs acting on the inflammatory cells implicated in TRLV pathogenesis.

Imatinib mesylate, a new kid on the block for the treatment of anti-neutrophil cytoplasmic autoantibodies-associated vasculitis?

Persistent T cell activation is a common finding in anti-neutrophil cytoplasmic autoantibodies (ANCA)-associated systemic vasculitis (AAV) patients. Because imatinib, a selective inhibitor of the ABL, ARG, PDGFR and c-KIT tyrosine kinases, inhibits T cell activation, this study was conducted to evaluate the potential use of imatinib for the treatment AAV patients refractory to conventional therapy. In particular, we investigated the inhibition of T cell activation by this drug and its efficacy on activated T cells from anti-neutrophil cytoplasmic autoantibodies (ANCA)-associated systemic vasculitides (AASV) patients. T cell stimulation has been induced by anti-CD3/anti-CD28 antibodies or by phorbol myristate acetate (PMA)/ionomycin. T cell proliferation was analysed by tritiumthymidine incorporation. Cell cycle progression was determined by propidium iodide staining using fluorescence activated cell sorter (FACS) analysis and by RNAse protection assay (RPA). Cytokine levels were assessed by enzyme-linked immunosorbent assay. T cell proliferation was inhibited significantly by imatinib, due most probably to cell cycle arrest in the G1-phase. This was paralleled by inhibition in the expression of cyclin-dependent kinases 1 and 2 mRNA. The expression of CD25 in naive and memory T cells was decreased significantly by imatinib in activated T cells. Similarly, conversion from naive to memory T cells after T cell activation was impaired by imatinib. Imatinib did not influence interleukin-2 and tumour necrosis factor-alpha production but increased interferon-gamma production. These observed effects of imatinib were similar in T cells from AASV patients and from healthy individuals. Imatinib might be an alternative therapeutical option for AASV patients refractory to conventional therapy.

Diagnostic Classification. of Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitides

Antineutrophil cytoplasmic autoantibodies (ANCA) are in the circulation of patients with a variety of clinically and pathologically distinctive forms of necrotizing vasculitis. Some patients have classic manifestations of well-recognized clinicopathologic syndromes, such as Wegener's granulomatosis, microscopic polyarteritis nodosa, and Churg-Strauss syndrome, but many patients are difficult to assign to a diagnostic category. The Ad Hoc Nomenclature Committee of The Third International Workshop on ANCA is attempting to identify a working classification system for ANCA-associated vasculitides. This system takes into account the many shared clinical and pathologic features, and relies on prerequisite positive and negative findings for diagnostic categorization.