Wegener's Granulomatosis Research Articles

Correction to: Nation-wide cohort study of remission induction therapy using rituximab in Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis: Effectiveness and safety in the first 6 months.

Correction to: Nation-wide cohort study of remission induction therapy using rituximab in Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis: Effectiveness and safety in the first 6 months.

Comparison of different ANCA detection methods in a predominantly MPO-ANCA-associated vasculitis cohort

We compared different antineutrophil cytoplasmic antibody (ANCA) detection methods using a predominantly myeloperoxidase (MPO)-ANCA-associated vasculitis cohort. Stored sera from 147 patients with untreated ANCA-associated vasculitis (AAV), including microscopic polyangiitis and granulomatosis with polyangiitis (n = 115 and 32, respectively), and 124 disease controls were tested for P-ANCA and C-ANCA with immunofluorescence (IIF), and for MPO-ANCA and proteinase 3 (PR3)-ANCA with different antigen-specific immunoassays: direct enzyme-linked immunosorbent assay (ELISA), chemiluminescent enzyme immunoassay (CLEIA), third-generation fluorescent enzyme immunoassay (FEIA), and latex turbidimetrical immunoassay (LTIA). In addition, MPO-ANCA and PR3-ANCA titers were calibrated using certified reference materials (CRMs). The sensitivities and specificities for AAV diagnoses were 95% and 94% (IIF), 86% and 98% (ELISA), 93% and 94% (CLEIA), 92% and 96% (FEIA), and 68% and 88% (LTIA). Dual IIF/antigen-specific immunoassay testing reduced diagnostic accuracies from 94% to 93%. The quantitative agreement between ANCA levels measured using CLEIA and FEIA and calibrated using CRMs was not good. In conclusion, this study demonstrated the high performance of antigen-specific immunoassays for AAV diagnosis in a predominantly MPO-ANCA-associated vasculitis cohort and suggested that the benefit of dual IIF/antigen-specific immunoassay testing is limited. Standardizing ANCA measurements using different immunoassays was difficult, even when using CRMs.

Serum Glial Fibrillary Acidic Protein Can Predict Cross-Sectional Vasculitis Activity by Reflecting Renal Involvement in Patients with Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

Background and Objectives: Glial fibrillary acidic protein (GFAP) is a type III intermediate filament protein primarily produced by cells in the central nervous system (CNS) and other major organs such as the kidneys. This study investigated whether serum GFAP could be used to estimate cross-sectional vasculitis activity presented via the Birmingham vasculitis activity score (BVAS) in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Materials and Methods: This study included 74 patients with AAV. Clinical and laboratory data at diagnosis including BVAS and C-reactive protein (CRP) were reviewed. During follow-up, all-cause mortality and end-stage kidney disease (ESKD) were considered poor outcomes. Serum GFAP was measured from sera collected and stored at diagnosis. Results: The median age of the 74 patients was 63.5 years. Serum GFAP was inversely correlated with the cross-sectional BVAS (r = -0.373) and CRP (r = -0.320). It was also significantly correlated with general (r = -0.237) and renal (r = -0.335) manifestations among BVAS systemic items, and furthermore, among minor items of renal manifestation, correlating with sum scores for proteinuria (r = -0.409) and haematuria (r = -0.305). Additionally, compared with patients with serum GFAP > 194.9 pg/mL, those with serum GFAP ≤ 194.9 pg/mL showed a higher risk for progression to ESKD (relative risk 3.150) and a significantly lower cumulative ESKD-free survival rate. Conclusions: This study demonstrated the clinical potential of serum GFAP at diagnosis for predicting not only cross-sectional vasculitis activity through the anticipation of the extent of renal involvement but also future progression to ESKD in patients with AAV.

8220 Panhypopituitarism due to Granulomatosis with Polyangiitis - Wegener's Granulomatosis. A Very Rare Cause of Panhypopiturism: A Case Report

Abstract Disclosure: T.D. Bertolacini da Silva: None. V.S. da Silva: None. P.R. Fiorin: None. J.S. Freire: None. C.G. Braga: None. M. Canzian: None. C. Machado: None. Background: Granulomatosis with Polyangiitis (GPA) is a necrotizing granulomatous vasculitis and pituitary involvement is less than 1%. We report a case of pituitary involvement, with CDI, and later panhypopituitarism. Clinical Case: A 43-year-old man was admitted in a hospital due to a headache 3 months ago. CT showed an expansive lesion in posterior fossa and hydrocephaly. Submetted for withdrawal of a Schwannoma and peritoneal shunt, with ipsilateral peripheral facial paralysis. After 1 year, started with polyuria and polydipsia, CDI was diagnosed and DDAVP started. Pituitary MRI showed a small rounded image in the sella turcica, cystic, 0.8 x 0.5 x 0.8cm. After 6 months, readmitted on hospital after trauma in surgical scar, with abscess, accomplished debridement and started oxacillin, with good controls of electrolytes and diuresis: Na 144 mmol/L (137-145 mmol/L). Readmitted after 2 months for surgical wound infection, on that occasion hyponatremia was diagnosed. Other tests were requested: TSH < 0.0015 uIU/mL (0.49-5.58 uIU/mL/mL), free T4 0.68 ng/dL (0.89-1.53 ng/dL), repeated TSH 0.036 uIU/mL and free T4 0.63 ng/dL, central hypothyroidism has been confirmed and levothyroxine started. Pituitary MRI was repeated with enlarged adeno-pituitary: 1.9 x 1.7 x 1.1cm, extension to the suprasellar cistern, compression, and superior displacement of the optic chiasm. Other tests: GH 0.173 ng/mL (< 3 ng/mL), IGF1 66 ng/mL (58-219 ng/mL), testosterone < 7.30 ng/dL (12-59 ng/dL), LH 0.1 mIU/mL (1.9-12.5 mIU/mL), prolactin 0.66 ng/mL (2.1-17.7 ng/mL), ACTH 6.66 pg/mL (< 46.0 pg/mL), confirmed pan-hypopituitarism. After 1-month patient started with petechiae and persisted with hyponatremia, SIADH hypothesis made. Chest CT showed a solid pulmonary nodule, spiculated, 2.6 x 2.1 x 1.8cm, first biopsy was inconclusive. After repeating the chest CT there was persistence the pulmonary nodule 4.2 x 5.8 x 4.4cm. Videothoracoscopy was perfomed and anatomopathological confimed GPA and C-ANCA positive. The patient received prednisone, ivermectin, pulse therapy (methylprednisolone) and cyclophosphamide. After 8 months admitted on hospital due to pneumonia and exogenous Cushing's syndrome, new tests were requested: pituitary MRI showed a hypocontrasting and heterogeneous on the sellar cavity 0.4 x 0.7 x 1.0cm, showing reduction of the lesion after treatment of the rheumatological disease. Patient also received treatment with Rituximab and the last pituitary MRI: hypocontrasting lesion, sometimes with a cystic appearance in the sellar cavity. Currently, in use: testosterone replacement, desmopressin prednisone, levothyroxine, rosuvastatin/ezetimib, cholecalciferol, colchicin and ibandronate sodium. He presented with an improved quality of life. Conclusion: GPA should be considered in cases of CDI and hypopituitarism when sellar disorders were discarded, and if a vasculitis is suspected. Presentation: 6/1/2024

Urine epidermal growth factor as a biomarker for kidney function recovery and prognosis in glomerulonephritis with severe kidney function impairment.

Prognostication in glomerulonephritis with severe kidney function impairment is critical for evaluating the benefit-to-risk ratio of immunosuppression. We hypothesized that the urine biomarker epidermal growth factor (EGF) could have good discrimination powerto identify subjects who might ultimatelyrecover kidney function. We included 82 subjects with glomerulonephritis and severe kidney function impairment at admission (estimated glomerular filtration rate [eGFR] ≤ 30mL/min/1.73m2): 58 with lupus nephritis (LN) and 24 with ANCA-associated vasculitis (AAV). Thirty-five subjects requiredkidney replacement therapy (KRT) at presentation. Urine epidermal growth factor was measured and corrected by urine creatinine (uEGF/Cr) and the population was analyzed by uEGF/Cr tertiles. The primary outcome was time to recovery of eGFR ≥ 30mL/min/1.73m2 and time to recovery of kidney function with dialysis independence in those with initial KRT. Forty-four (54%) participants met the primary outcome of recovery of eGFR ≥ 30mL/min/1.73m2. The 6-month recovery rates were 93%, 57%, and 0% for participants in the highest, middle, and lowest uEGF/Cr tertile, respectively. Recovery of thekidney function was faster and ledto a higher post-therapy eGFR in the highest uEGF/Cr tertile. In the ROC analysis,uEGF/Cr was a predictor of recovery with an area under the curve (AUC) of 0.92 (95% CI 0.87-0.98), and a cutoff of 2.60ng/mg had 100% sensitivity to detect patients who recovered kidney function. In the subgroup of participants with initial KRT,the cut-off of uEGF/Cr of 2.0ng/mg had 100% sensitivity to detect participants who recovered kidney function with dialysis independence by 6months. Urine EGF/Cr is a promising biomarker to aid in the prediction of recovery of kidney function in glomerulonephritis with severe kidney function impairment.

Pneumatosis cystoides intestinalis in granulomatosis with polyangiitis: a case report.

This study aims to investigate the clinical manifestations, imaging features, and treatment considerations in the rare occurrence of pneumatosis cystoides intestinalis (PCI) within the context of granulomatosis with polyangiitis (GPA). We present the case of a 71-year-old Chinese woman diagnosed with GPA, who, despite exhibiting fatigue, knee pain, and nasosinusitis, remained asymptomatic for PCI. Regular follow-up revealed laboratory and imaging evidence indicative of clinical relapse. The patient received GPA treatment but was not specifically managed for PCI. Serial abdominal CT scans were performed to monitor the progression of PCI. Radiological diagnosis confirmed the presence of gas within the colon wall, indicating pneumatosis cystoides intestinalis. Notably, the patient remained asymptomatic for abdominal complaints. Despite ongoing GPA treatment, a follow-up CT scan 2months later revealed persistent gas within the colon wall, suggesting a persistent state of PCI. Patient consent was obtained for the publication of this case report, and ethical approval was not obtained as this study constitutes a retrospective review. This case underscores the importance of recognizing pneumatosis cystoides intestinalis as a potential complication in GPA patients, even in the absence of typical abdominal symptoms. Further research is warranted to elucidate the underlying mechanisms and optimal management strategies for this rare association. Key points • Rare association: This case report sheds light on the uncommon occurrence of pneumatosis cystoides intestinalis (PCI) within the context of granulomatosis with polyangiitis (GPA), adding to the understanding of the spectrum of manifestations of GPA. • Clinical manifestations: Despite being diagnosed with GPA and experiencing symptoms such as fatigue, knee pain, and nasosinusitis, the patient remained asymptomatic for PCI, emphasizing the importance of vigilant clinical monitoring in GPA patients. • Imaging features: Radiological imaging, including serial abdominal CT scans, played a crucial role in diagnosing and monitoring the progression of PCI in the absence of typical abdominal complaints, highlighting the utility of imaging modalities in detecting silent manifestations of gastrointestinal complications in GPA. • Treatment considerations: The case highlights the challenge of managing PCI in GPA patients, especially when asymptomatic, and raises questions about the optimal management strategies for such rare associations, underscoring the need for further research in this area.

B-074 Comparative Evaluation of Clinical Utility between Indirect Immunofluorescence and Immunoassay Methods for Antineutrophil Cytopalsmic Antibody Detection

Abstract Background ANCA testing is essential for the diagnosis of vasculitis, commonly using indirect immunofluorescence(IIF) and immunoassay(IA) methods. Recent guidelines recommend IA as the primary test for suspected GPA and MPA, but actual practice varies among physicians. Here, we retrospectively analyzed ANCA test results, focusing on new cases of ANCA-associated vasculitis, and compared the utility of IIF and IA to guide appropriate test selection. Methods From January 2022 to July 2023, 24 new cases of ANCA-associated vasculitis were diagnosed. We checked whether ANCA testing was performed and the results, and compared the turnaround time(TAT) and costs. IIF ANCA tests were performed on a computer-based automated instrument(Helios), and IA ANCA tests were performed on automated instruments(Alegria, Phadia 250) with MPO antigen and PR3 antigen tested simultaneously in a bundled prescription. Results Among the 24 cases, there were 6 GPA, 7 MPA, 7 EGPA, and 4 ANCA-associated GN, with varying diagnostic sensitivities. GPA and EGPA had different ANCA positivity rates than previously reported, suggesting potential ethnic variations in ANCA expression and positivity rates. The test sequence and results, summarized in Table 1, showed 21 out of 22 cases had identical concordance between methods, with an excellent concordance rate (kappa value=0.83). TAT for IIF was 3,452 minutes, and for IA was 1,491 minutes for the whole period, but IA TAT increased to 2,748 minutes after implementing a days-of-the-week testing system. Test costs, with a relative value score of 118.99 for IIF and 156.05 for IA, indicated IA cost approximately 2.6 times higher, considering the bundled prescription of both antigens for IA ANCA testing. Conclusions Evaluating the utility of both methods for ANCA detection, our study highlights high inter-method agreement in ANCA-associated vasculitis. Considering overall cost and turnaround time, IIF ANCA testing remains effective as a screening test, demonstrating standalone effectiveness.

The real-world use and effectiveness of avacopan in routine practice for the treatment of ANCA vasculitis. First experiences in Spain.

ANCA-associated vasculitis (AAV) are chronic diseases with relapses that associate organic damage because of the disease and its treatment. Avacopan is a new treatment indicated for AAV. We present the first experiences with avacopan in Spain as part of an Early Access program. Patients with AAV who started avacopan between June 2022-September 2023 were included. For comparison, a historical cohort of patients diagnosed with AAV around the same time and treated without avacopan was also included. 29 patients treated with avacopan were analyzed. Twelve patients (41.4%) were male, median age was 56 years. Most of patients were ANCA MPO positive (21/29, 72.4%). The most frequently affected organ was the kidney (23/29, 79.31%), with a mean eGFR of 23.2 ml/minMedian follow-up was 456.8 ± 181.7 days with a remission rate of 86.2%. eGFR increased from 23.2 ± 11.2-38.38 ± 18.55 ml/min after 12 months of diagnosis.2 patients had Adverse Events related to avacopan as severe neutropenia and a gastrointestinal affectation , 13 infections were reported and 1 death.Patients treated with avacopan received a significantly lower cumulative dose of prednisone at 6 and 12 months (p-values of 0.02 and <0.01, respectively) compared with historical controls. The evolution of GFR at 1 year of follow-up and the incidence of relapse were similar in both groups. The combination of avacopan in clinical practice presents a good safety profile and provides added value by contributing to the control of AAV activity, increase GFR, and removal of steroids.

C ANCA Antibodies and Infective Endocarditis -Friends Or Foes?

Abstract The differential diagnosis between granulomatosis with polyangiitis (GPA) and infective endocarditis (IE) is crucial. Both diseases show clinical similarities and serologic c-ANCA overlap. We present the case of a 45-year-old patient with inflammatory and anemic syndrome, c-ANCA positivity and initial respiratory and renal symptoms that raised the suspicion of GPA. Subsequent evolution revealed severe valve involvement and the presence of Streptococcus gallolyticus in blood cultures, confirming the diagnosis of infective endocarditis. Antibiotic treatment and surgical intervention were crucial for the patient’s recovery. This case demonstrates the importance of imaging and microbiological examinations for the correct differentiation of these diseases and the importance of a multidisciplinary approach.

Anti-neutrophil CytoplasmAntibody-Associated Vasculitis as Paraneoplastic Glomerular Disease

Anti-neutrophil CytoplasmAntibody-Associated Vasculitis as Paraneoplastic Glomerular Disease

ANCA-Associated Vasculitis with Atypical Findings of Renal Medullary Angiitis

ANCA-Associated Vasculitis with Atypical Findings of Renal Medullary Angiitis

Elicitation of Physician Opinions of the Impact of Dynamic Changes in Biomarkers on Perceived Relapse Propensity in ANCA-Associated Vasculitis: Impact of Individual Expert and Patient Characteristics

Elicitation of Physician Opinions of the Impact of Dynamic Changes in Biomarkers on Perceived Relapse Propensity in ANCA-Associated Vasculitis: Impact of Individual Expert and Patient Characteristics

Clinical Phenotype Identifies Individuals with ANCA-Associated Vasculitis Who Do Not Require Kidney Biopsies for Diagnosis of Kidney Involvement

Clinical Phenotype Identifies Individuals with ANCA-Associated Vasculitis Who Do Not Require Kidney Biopsies for Diagnosis of Kidney Involvement

Rare Coincidence or Secondary Process: Membranous Nephropathy with ANCA-Associated Vasculitis

Rare Coincidence or Secondary Process: Membranous Nephropathy with ANCA-Associated Vasculitis

Outcomes after Kidney Transplantation in ANCA-Associated Vasculitis

Outcomes after Kidney Transplantation in ANCA-Associated Vasculitis

Urinary Complements as a Predictor of Kidney Outcomes in Patients with ANCA-Associated Vasculitis

Urinary Complements as a Predictor of Kidney Outcomes in Patients with ANCA-Associated Vasculitis

Siglec-9 and Its Ligand in ANCA-Associated Vasculitis

Siglec-9 and Its Ligand in ANCA-Associated Vasculitis

Rare Biopsy Findings of IgA and C3 on Immunofluorescence in ANCA-Associated Vasculitis

Rare Biopsy Findings of IgA and C3 on Immunofluorescence in ANCA-Associated Vasculitis

Acute Rejection and Relapse of Native Disease in Kidney Transplant Recipients with ESKD from ANCA-Associated Vasculitis: Insights from a Single-Center Study

Acute Rejection and Relapse of Native Disease in Kidney Transplant Recipients with ESKD from ANCA-Associated Vasculitis: Insights from a Single-Center Study

Long-Term Kidney Outcomes in ANCA-Associated Vasculitis in a Mexican Hispanic Cohort

Long-Term Kidney Outcomes in ANCA-Associated Vasculitis in a Mexican Hispanic Cohort