anti-GBM Levels Research Articles

B-107 Serodiagnosis of Anti-glomerular Basement Membrane Disease Using a Newly Developed Chemiluminescence Immunoassay

Abstract Background Autoantibodies against the glomerular basement membrane (GBM) are important markers in the diagnosis and monitoring of autoimmune glomerulonephritides. Fast and reliable detection of these autoantibodies is crucial as anti-GBM disease can progress rapidly with fatal outcome. Here, we investigated the diagnostic performance of a newly developed, standardized anti-GBM chemiluminescence immunoassay (ChLIA). Methods The diagnostic performance of the EUROIMMUN Anti-GBM ChLIA (IgG), processed on the EUROIMMUN RA Analyzer 10, was assessed using sera from 67 clinically characterized anti-GBM disease patients and 221 disease controls. Results were compared with those obtained by the EUROIMMUN Anti-GBM ELISA (IgG). Inter-assay concordance, measurement range and interference were determined in a subset of samples. Results The ChLIA reached 100% sensitivity at a specificity of 98.6%, while the ELISA was less sensitive (89.6%) and more specific (100%). High qualitative concordance between both assays was evidenced by positive and negative agreement rates of 100% and 95.6%, respectively, and a kappa score of 0.901. The ChLIA showed linearity within a measurement range of 3.8–517.3 CU/mL. Coefficients of variation were calculated as 1.2%–3.3% (intra-lot) and 1.6%–4.2% (inter-lot). No interference was observed for hemolyzed, lipemic or icteric samples. Conclusion These validation results demonstrate a high quality of the novel Anti-GBM ChLIA. Given its excellent performance compared to the corresponding ELISA, it represents a promising alternative tool for accurate anti-GBM assessment in routine diagnostic settings with the advantage of rapid turnaround time and fully automated random-access processing. Future studies will address the assay’s suitability for monitoring anti-GBM levels during follow-up.

Clinicopathological characteristics and predictors of poor outcome in anti-glomerular basement membrane disease – a fifteen year single center experience

Introduction Anti-glomerular basement membrane (anti-GBM) disease is a small vessel vasculitis affecting the renal and lung capillary beds. We aim to study the clinicopathological characteristics and predictors of poor outcome of this disease in our population. Materials and methods This is a 15 year retrospective, single center observational study of Indian cohort. Patients with biopsy proven anti-GBM disease were studied. Results Anti-GBM disease was found in 0.5% of the total cases. The mean age at presentation was 46.7 years. Compared to renal limited disease those with pulmonary-renal syndrome had a higher frequency of hypertension, oliguria, percentage of crescents, interstitial inflammation and glomerulosclerosis. Double positive (anti-GBM and ANCA antibodies) patients showed more of glomerulosclerosis, tubular atrophy/interstitial fibrosis (IFTA) as well as periglomerular granulomas on biopsy. Patient survival at one year was 40.4% and death censored renal survival was 9.7%. Factors affecting the dialysis dependency at presentation were oligoanuria (p = .04), creatinine levels >5.7 mg/dl (p = .003), and high mean anti-GBM titers (p = .008). Atypical cases accounted for 8.3% of these patients. Oligoanuria (HR = 5.0, p = .05), high serum creatinine (HR = 1.55, p = .05), severe glomerulosclerosis (HR = 1.09, p = .03), and IFTA (HR = 2, p = .04) were associated with poor renal outcome. Advanced age (HR = 1.92, p = .03), high serum creatinine (HR = 1.9, p = .04) and high anti-GBM titers (HR = 1.01, p = .03) were associated with poor patient survival. Conclusions Anti-GBM is a rare disease with poor prognosis and varied presentations. Patients with pulmonary-renal syndrome showed severe disease whereas double positive had more of chronic changes. The predictors of poor prognosis include advanced age, oliguria, serum anti-GBM levels, serum creatinine levels, degree of glomerulosclerosis and IFTA. Atypical anti-GBM cases should be kept in mind while evaluating renal biopsies.

P0485ASSOCIATION BETWEEN ANTI-GBM TITERS AND KIDNEY INFLAMMATION MEASURED BY A NEW ACTIVITY SCORE

Abstract Background and Aims Anti-glomerular basement membrane (anti-GBM) disease is an aggressive and rare glomerulopathy characterized by rapidly progressive loss of kidney function, leading to end stage kidney disease (ESKD) in a significant amount of cases. The main objective of our study was to determine whether anti-GBM titer correlated with the rate of activity in renal biopsy and long-term kidney survival in patients with anti-GBM, hence identifying patients who would potentially benefit from more intensive treatments. Method A retrospective analysis was performed on the cases of anti-GBM from our center that had both a positive biopsy and serology, from 2007 to 2019. Epidemiological data, anti-GBM levels on admission, kidney function at admission, discharge and follow-up, treatment and kidney biopsy findings were collected. All biopsies were reevaluated by a single, blinded pathologist and nephrologist. Based on a recent study by van Daalen et al, a chronicity and activity histopathological score was developed. The score was divided in glomerular and interstitial sections. In the glomerular section, a sclerotic pattern (>50% of glomeruli) was given 0 points in activity and 3 in chronicity, a mixed pattern was given 1 point in activity and chronicity, and a crescentic pattern (>50% with cellular crescents) was given 3 points in activity and 0 in chronicity. In the interstitial section, the presence of fibrosis and atrophy was given between 0 and 3 points in chronicity and the presence of tubulitis or interstitial infiltrate were given points in activity (0 to 1 and 0 to 3 respectively). The presence of neutrophils in the infiltrate was given one extra point in activity. Spearman correlation was performed between anti-GBM levels and our biopsy score. Results Twelve cases were identified, with a median Anti-GBM titer at admission of 292 U/mL (IQR 40-1517). Ten patients were treated with cyclophosphamide, 1 with rituximab plus cyclophosphamide and 1 with only rituximab. All patients received treatment with metilprednisona and plasma exchange with a median number of sessions of 8 (range: 6-12). Only one patient was not in ESKD during follow-up (35 months), so correlation with long-term kidney survival could not be performed. On the other hand, high antibody titers correlated with more activity on biopsy (correlation coefficient 0.592, p= 0.042) and less chronicity (correlation coefficient -0.657, p= 0.02). Conclusion These results suggest that patients who present with higher titers have more acute inflammation and less chronicity in renal parenchima, and therefore could benefit from more intensive treatment that changes the natural history of this aggressive disease. It would be interesting to study this score in larger and multicentric cohorts in order to produce more definitive conclusions.

Hepatitis C-associated glomerulonephritis masquerading as Goodpasture’s syndrome

Anti-glomerular basement membrane (GBM) autoantibodies are associated with Goodpasture’s syndrome, characterised by lung and kidney involvement. We report a case with clinical disease demonstrating discrepant anti-GBM antibody results between assay platforms. A 39-year-old male presented with an eight-week history of haemoptysis and acute renal impairment, on a background of active hepatitis C infection. Creatinine was 256 μmol/L with haemoproteinuria, hypocomplementaemia, and positive anti-GBM level (65 U/mL Phadia ELiA; reference range >10 U/mL) which was confirmed on repeat testing. Treatment for Goodpasture’s syndrome was initiated with plasma exchange (PLEX) and intravenous cyclophosphamide. However, renal biopsy performed in parallel to treatment did not demonstrate characteristic linear GBM binding on direct immunofluorescence. Findings were instead consistent with hepatitis C-associated glomerulonephritis. ANCA by immunofluorescence was negative. Anti-PR3, anti-MPO and anti-CCP tested retrospectively by Phadia ELiA methods were also positive, raising suspicion for an interfering factor. Pre-treatment sera tested for anti-GBM antibodies via indirect immunofluorescence (INOVA primate kidney) and chemiluminescence assay (INOVA BIO-FLASH) were negative. Unfortunately, pre-treatment cryoglobulins had not been tested. However, testing 6 months after presentation confirmed type 2 cryoglobulins, and anti-GBM levels had normalised. Cryoglobulins or another interfering factor may have caused platform-specific assay interference, affecting anti-GBM and other autoantibody detection on the same platform.

Maternal, pregnancy and fetal outcomes in de novo anti-glomerular basement membrane antibody disease in pregnancy: a systematic review.

BackgroundOutside of pregnancy, anti-glomerular basement membrane (GBM) antibody disease is associated with significant morbidity and mortality. However, there is limited knowledge regarding de novo anti-GBM disease in pregnancy.MethodsA systematic review was performed to identify maternal, pregnancy and fetal outcomes in de novo anti-GBM disease in pregnancy. Studies were selected from PubMed, EMBASE, Cochrane Library databases and conference proceedings, without language restriction.ResultsData from eight patients were derived from seven case reports and one unpublished case. Most (6/8) patients presented after the first trimester. During pregnancy, acute kidney injury (5/8), anemia (5/8), hematuria (8/8) and proteinuria (8/8) were common. When hemodialysis was required antepartum (5/8), renal function recovery to independence of renal replacement was unlikely (2/5). While pulmonary involvement was common (5/8), no permanent damage was reported (0/8). The majority of cases ended in live births (6/8) although prematurity (6/6), intrauterine growth restriction (2/6), small for gestational age (4/6) and complications of prematurity (1/6) were common. When anti-GBM levels were tested in the living newborn, they were detectable (2/5), but no newborn renal or lung disease was reported (0/6). Complications in pregnancy included gestational diabetes (3/8), hyperemesis gravidarum (2/8) and preeclampsia (2/8).ConclusionsLive births can be achieved in de novo anti-GBM disease in pregnancy, but are commonly associated with adverse maternal, pregnancy and fetal outcomes. Only with awareness of common presentations, and management strategies can outcomes be optimized.

PReS-FINAL-2299: Novel biomarkers for the assessment of pediatric systemic lupus erythematosus nephritis (preliminary report)

Results The pSLE nephritis patients had significantly higher serum levels of anti-NCS [median: 48.89 (IQR: 31.4880.81) U/ml versus 12.5 (11.5-27.8) U/ml, p < 0.001], anti-C1q [22.75 (12.77-56.4) U/ml versus 12.5 (12.512.5) U/ml, p < 0.001], anti-GBM [3.88 (2.25-6.94) U/ml versus 2.2 (2.2-2.4) U/ml, p = 0.002] and HMGB1 [9.9 (5.7-32.23) ng/ml versus 2.5 (2.5-2.5) ng/ml, p < 0,001], than the patients with nephritis of other causality. Serum anti-GBM levels were significantly higher in the pSLE nephritis patients compared to the pSLE patients without nephritis [3.88 (2.25-6.94) U/ml versus 2.25 (2.2-2.83) U/ml, p = 0.014], while this was not true for the rest of the biomarkers. In the pSLE nephritis patients no correlation was found between serum antiGBM levels and pSLE nephritis disease activity. Serum anti-NCS and anti-C1q levels were positively correlated with the ECLAM score in the pSLE patients as a whole (p = 0.002, rho = 0.492 and p = 0.007, rho = 0.461, respectively). Conclusion In this pure Caucasian Northern Greek pSLE population, high serum anti-GBM levels were found to be associated with the presence of nephritis, but not with the nephritis disease activity. Serum anti-GBM, anti-NCS, anti-C1q and HMGB1 may be used to differentiate patients with pSLE nephritis from patients with nephritis of other causality. Furthermore, serum anti-NCS and anti-C1q may be useful for the estimation of pSLE disease activity.

SAT0473 Novel Biomarkers for the Assessment of Pediatric Systemic Lupus Erythematosus Nephritis (Preliminary Report)

BackgroundNephritis is the most common severe manifestation of pediatric Systemic Lupus Erythematosus (pSLE) and the major predictor of poor prognosis. Research for the detection of novel and accurate biomarkers, predictive...

Asymptomatic Autoantibodies Associate with Future Anti-glomerular Basement Membrane Disease

The pathophysiology of anti-glomerular basement membrane (anti-GBM) disease before clinical presentation is unknown. The presence of anti-GBM, anti-proteinase 3 (PR3), and anti-myeloperoxidase (MPO) antibodies associate with the disease at the time of diagnosis, but little is known about the presence of these autoantibodies before diagnosis. We used serum samples from the Department of Defense Serum Repository to conduct a case-control study involving 30 patients diagnosed with anti-GBM disease and 30 healthy controls matched for the age, gender, race, and age of the serum samples. We analyzed a maximum of three samples from each subject: the most recent sample before diagnosis, the penultimate sample before diagnosis, and the oldest sample available; the average time between the most recent sample and diagnosis was 195 days (range, 4 to 1346 days). Elevated anti-GBM levels (≥3 U/ml) were present in four patients, all less than 1 year before diagnosis but in no controls. Detectable anti-GBM antibody levels (≥1 U/ml but <3 U/ml) in a single serum sample before diagnosis were more frequent in cases than controls (70% versus 17%, P < 0.001). Only study patients had detectable anti-GBM levels in multiple samples before diagnosis (50% versus 0%, P < 0.001). Almost all patients had detectable anti-PR3 and/or anti-MPO that preceded the onset of disease. Among patients with a clear antecedent antibody, anti-PR3 or anti-MPO always became detectable before the anti-GBM antibody. In summary, our data describe the subclinical formation of autoantibodies, which improves our understanding of the pathophysiology of anti-GBM disease.