Welcome to the Autoimmunity 2021 Congress Calendar
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SYSTEMIC VASCULITIS: NEW TREATMENT APPROACHES
INTERNATIONAL CONSENSUS ON ANCA TESTING BEYOND SYSTEMIC VASCULITIS
Abstract
Background and Aims
ANCA positivity is a distinctive laboratory feature of ANCA-associated vasculitis. However, ANCA can be detected by antigen-specific immunoassays or indirect immunofluorescence (IIF) in patients with other autoimmune, inflammatory, infectious or neoplastic diseases. The aim was to issue a Consensus Statement on ANCA testing and interpretation beyond systemic vasculitis.
Methods
This Consensus Statement was prepared by a group of experts, including specialists in internal medicine, rheumatologists, nephrologists, gastroenterologists, hepatologists, pulmonologists, and clinical laboratory immunologists, based on the results of a comprehensive search in PubMed for disorders that can be associated with positive ANCA test results.
Results
Evidence suggests that ANCA may have diagnostic, clinical, and/or diagnostic relevance beyond systemic vasculitis. Testing for proteinase-3 ANCA and myeloperoxidase-ANCA should be performed in any patient with clinical features suggesting ANCA-associated vasculitis and in patients with anti-GBM disease, idiopathic interstitial pneumonia, and infective endocarditis complicated by nephritis, whereas routine ANCA testing is not recommended in connective tissue diseases, autoimmune liver diseases, inflammatory bowel diseases, infections, and/or various forms of malignancy. ANCA testing may be justified in patients with suspected autoimmune hepatitis type 1, who do not have conventional disease-related autoantibodies, or in patients with inflammatory bowel diseases in case of diagnostic uncertainty to discriminate ulcerative colitis from Crohn’s disease. In these cases, ANCA should be tested by IIF since target antigens are not yet well characterized
Conclusions
ANCA testing is clinically relevant not only in patients with manifestations suggesting systemic vasculitis, but also in patients with certain other disorders, particularly in patients with anti-GBM disease or idiopathic interstitial pneumonia.
THE ASSOCIATION BETWEEN GIANT CELL ARTERITIS AND HEMATOLOGIC MALIGNANCIES
CLINICAL ASSOCIATIONS OF RENAL INVOLVEMENT IN ANCA-ASSOCIATED VASCULITIS
Abstract
Background and Aims
Renal involvement in anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis is associated with significant morbidity and higher mortality rates. This study examined clinical manifestations associated with renal involvement in ANCA-associated vasculitis within a large, international cross-sectional cohort.
Methods
Univariate and multivariate analyses were performed to identify clinical factors associated with renal disease, which was defined as i) a serum-creatinine > 30% above normal and a fall in creatinine-clearance > 25%; or ii) haematuria attributable to active vasculitis.
Results
The study cohort include 1230 patients from 31 countries; 723 (58.8%) presented with renal involvement: microscopic polyangiitis (82.2%), granulomatosis with polyangiitis (58.6%), and eosinophilic granulomatosis with polyangiitis (26.4%). The following clinical and laboratory factors were more common among patients with renal disease: age (p=0.001), fever (p<0.001), fatigue (p=0.005), weight loss (p=0.001), polyarthritis (p=0.036), petechiae/purpura (p=0.022), pulmonary haemorrhage (p=0.014), gastrointestinal symptoms (p=0.002), seizures (p=0.016), lower serum albumin (p<0.001), higher CRP (p=0.038), low serum C3 at baseline (p=0.015), myeloperoxidase- (p<0.001) and proteinase 3-ANCA (p=0.020). The following clinical factors were less common among patients with renal disease: mononeuritis multiplex (p=0.041), proptosis/exophthalmos (p=0.001), nasal polyps, septal defect/perforation (p<0.001 each), respiratory distress/pulmonary fibrosis/asthma (p<0.001), and wheeze/obstructive airway disease (p<0.001).
Conclusions
In this large international study, several clinical and laboratory factors were identified as associated with renal involvement in ANCA-associated vasculitis.
BIRMINGHAM VASCULITIS ACTIVITY SCORE AND DISEASE EXTENT INDEX AS A DISEASE ASSESSMENT TOOLS IN CRYOGLOBULINEMIC VASCULITIS
Abstract
Background and Aims
The Birmingham Vasculitis Activity Score (BVAS) and Disease Extent Index (DEI) are used in the assessment of vasculitis. The aim of this study was to evaluate the BVAS and DEI in patients with differing degrees of disease severity and different etiologies of cryoglobulinemic vasculitis (CV).
Methods
The BVAS and DEI were evaluated at initial presentation and after a follow up period of 6 to 120 months in patients with mild CV (44), severe CV (49), essential mixed cryoglobulinemia (34), non-infectious cryoglobulinemia (38) and hepatitis C virus (HCV)-related cryoglobulinemia (17). The correlations between BVAS and DEI with different serological parameters were examined.
Results
Both the BVAS and DEI were significantly higher in patients with severe CV (p<0,01). There was a correlation observed between a patient’s BVAS and cryoglobulin concentration (p<0,01) and decreased complement levels (p<0,01). The DEI correlated with decreased complement levels (p<0,01). After the follow up period, the BVAS was significantly lower (p<0,01) in both severe and a mild form of CV. There was no difference in either BVAS or DEI in patients with different etiologies of CV. After the follow up period, patients with HCV-related cryoglobulinemia had a significantly higher BVAS and DEI.
Conclusions
A correlation was found between BVAS, cryoglobulin concentration and decreased complement levels. The patients with severe CV showed significant decrease in their BVAS after the follow up period. The patients with HCV-related cryoglobulinemia demonstrated a significantly higher BVAS and are seven times less likely to present a decrease in BVAS during the treatment period (OR 6,801; CI 95%).
VARIABILITY OF CLINICAL CHARACTERISTICS AND OUTCOMES OF PATIENTS WITH ANCA-ASSOCIATED VASCULITIDES IN A LATIN-AMERICAN HOSPITAL
Abstract
Background and Aims
ANCA-associated vasculitis (AAV) are necrotizing vasculitis, predominantly affecting small vessels, and associated with ANCA specific for myeloperoxidase (MPO-ANCA) or proteinase 3 (PR3-ANCA), with a very varied clinical spectrum. This study aimed to describe the clinical characteristics of patients with ANCA-associated vasculitis (AAV) in the first disease presentation and the ultimate clinical control. Besides to determine serological characteristics, treatment, and outcomes.
Methods
A total of 68 patients with AAV diagnosed between January 2011 and June 2019, in a high-complexity Hospital in Cali - Colombia was retrospectively analyzed. The activity was established using the Birmingham Vasculitis Activity Score (BVAS).
Results
Altogether, 60.2% had granulomatosis with polyangiitis (GPA), 19.1% microscopic polyangiitis (MPA), and 17,6% eosinophilic granulomatosis with polyangiitis (EGPA). The mean age at diagnosis was 50,3 ± 15,4 years in GPA, 50,2 ± 14,5 years in MPA, and 49,2 ± 14,7 years in EGPA. Arthralgia and ear-nose-throat (ENT) symptoms were the most common at disease onset (Figure 1). The initial BVAS was 12 (3-18) in GPA patients. Outcomes were variable, 11 patients with end-stage chronic renal failure, and five patients requiring renal transplantation.
Conclusions
The prevalence of AAV and the clinical characteristics in Latin-American patients are unknown; for that reason, these studies are necessaries.
THE PATHOGENIC ROLE OF CIRCULATING HASHIMOTO'S THYROIDITIS-DERIVED TPO POSITIVE IGG ON FETAL DEVELOPMENT IN NAÏVE MICE: RESULTS OF PRELIMINARY STUDY
Abstract
Background and Aims
Antibody-mediated-autoimmune-diseases such as autoimmune thyroid diseases (ATD), systemic-lupus-erythematosus (SLE) and antiphospholipid-syndrome (APS), often are associated with abnormalities of fetal development and recurrent fetal loss. One of the ATD is Hashimoto's thyroiditis which recently showed association with complications of pregnancy with increased levels of circulating autoantibodies reactive with epitopes on thyroid tissue such as thyroid peroxidase (aTPO). In retrospective study of sera analyses in patients with Hashimoto's thyroiditis, all patients had elevated circulating aTPO autoantibodies, whereas about 50% of patients with circulating autoantibodies targeting thyroglobulin or thyroid stimulating hormone antibodies (anti-TSH).We assessed the potential of human anti-TPO highly positive IgG, derived from patients with Hashimoto's thyroiditis sera, to cause directly complications of pregnancy in murine experimental model.
Methods
Naïve ICR female mice, were infused with aTPO, or control IgG. Pregnancy development was followed.Results
Infusion of aTPO-IgG showed increased fetal loss and embryo small for date, (p<0.001) in comparison to mice passively transferred with commercial IgG, or PBS. Moreover, the aTPO-IgG subjected mice, showed reduced weight of embryos and placentae (p=0.001). Histopathological examination revealed delay in fetal development in 50% cases of aTPO- IgG treated mice. Importantly, pathological changes in the transition zone, state of glycogen cells and significant structural changes in the labyrinth part of placenta were observed in all aTPO-IgG samples.Conclusions
Our study shows for the first time, a direct proof of concept, on the pathogenic role of aTPO-IgG in induction of murine fetal loss, association of fetal loss in patients with Hashimoto's thyroiditis.THE VALUE OF ANTI-NEUTROPHIL CYTOPLASMIC ANTIBODIES (ANCA) TESTING FOR THE DIAGNOSIS OF ANCA-ASSOCIATED VASCULITIS, A SYSTEMATIC REVIEW AND META-ANALYSIS
Abstract
Background and Aims
The testing of anti-neutrophil cytoplasmic antibodies (ANCA) takes an important place in the diagnostic workup to ANCA-associated vasculitis (AAV). Nowadays, it is recommended to screen for the presence of PR3 and MPO specific antibodies first using immunoassay, without the need for ANCA measurement by indirect immunofluorescence (IIF).
Methods
A literature search was performed to assess the diagnostic test value of ANCA IIF and PR3- and MPO-antibody immunoassay to diagnose AAV.
Results
This meta-analysis shows that the c-ANCA testing by IIF has a pooled sensitivity of 75.2% and a pooled specificity of 98.4%. For PR3-antibody immunoassay, the pooled sensitivity depended on the immunoassay method used, and ranged from is 79.8% to 86.6%, whereas the pooled specificity ranged from 96.8% to 98.3%. For both p-ANCA IIF and MPO-antibody immunoassay (all methods) sensitivity varied considerably showing pooled values of respectively 46.3% and 58.1%, whereas respective pooled specificity was 91.4% and 95.6%.
Conclusions
These findings support the 2017 international consensus that primary anti-PR3 and anti-MPO screening by immunoassay, based on superior immunoassay sensitivity without the need for IIF ANCA testing, improves the diagnostic workup of AAV