CD27+CD38hi B Cell Frequency During Remission Predicts Relapsing Disease in Granulomatosis With Polyangiitis Patients

Borstel, Anouk von; Land, Judith; Abdulahad, Wayel H.; Rutgers, Abraham; Stegeman, Coen A.; Diepstra, Arjan; Heeringa, Peter; Sanders, Jan-Stephan

doi:10.3389/fimmu.2019.02221

Cited by 32 publications

(35 citation statements)

References 37 publications

(46 reference statements)

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“…The ANCA test is useful in monitoring patients with persistently elevated ANCA, as those with a reappearance of ANCA or an increase in ANCA levels have an increased likelihood of relapse, although restarting or intensifying therapy based on ANCA alone is not recommended. This aligns with an association between earlier relapse and a higher frequency of memory B cells 163 , while a higher plasmablast percentage during remission is also predictive of relapse 164 . The acute-phase markers C-reactive protein and erythrocyte sedimentation rate are of limited use in evaluating disease activity due to their lack of specificity.…”

Section: Biomarkerssupporting

confidence: 81%

ANCA-associated vasculitis

Kitching

Anders

Basu

et al. 2020

Nat Rev Dis Primers

591

507

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The anti-neutrophil cytoplasmic antibody (ANCA)associated vasculitides (AAVs) are diseases characterized by inflammation of blood vessels, endothelial injury and tissue damage. The three types of small-vessel vasculitis, namely granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic GPA (EGPA; previously known as Churg-Strauss syndrome), feature a loss of tolerance to neutrophil primary granule proteins, most often leukocyte proteinase 3 (PR3; also known as myeloblastin) or myeloperoxidase (MPO) (Table 1). The vessels involved in AAV are typically capillaries, arterioles and venules but small arteries and veins may also be affected. Autoimmunity is documented clinically by serum ANCAs to PR3 (PR3-ANCA) or MPO (MPO-ANCA), which are generally associated with the main syndromic AAV presentations (box 1). AAVs collectively represent one of several types of autoimmune vasculitis (Fig. 1). GPA and MPA can involve small blood vessels in any organ or tissue but commonly affect the upper and lower respiratory tract and the kidneys (box 2). Patients with AAV typically present with severe organ-threatening or life-threatening disease, although less severe presentations also occur. GPA is predominantly associated with PR3-ANCA and its clinical features typically include sinonasal disease, lower respiratory tract involvement with pulmonary haemorrhage and granulomatous inflammation, and glomerulonephritis. MPA is usually associated with MPO-ANCA and clinical features include more severe renal disease and some of the manifestations of GPA but without granulomatous inflammation. EGPA is characterized by asthma, eosinophilia and, in many (but not all) cases, vasculitis. EGPA is less common than GPA or MPA and, in some cases, is associated with ANCAs, mainly MPO-ANCA (Table 1). Although categorized as a form of AAV, EGPA has less overlap with the other AAVs than that between GPA and MPA with regard to its genetic, pathogenetic, and clinical features and its management and is typically considered a separate entity. Improvements in treatment and prognosis for patients with AAV have resulted from the translation of both preclinical and clinical research findings. Here, we provide an updated overview of the clinical and

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Section: Biomarkerssupporting

confidence: 81%

ANCA-associated vasculitis

Kitching

Anders

Basu

et al. 2020

Nat Rev Dis Primers

591

507

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“…Although B cell count and ANCA titer increase are shown to be associated with relapse [35,36], these are not recommended for monitoring treatment [3]. Von Borstel et al have reported CD27 + CD38 hi B cell frequencies during remission were associated with the risk for relapse in GPA patients, suggesting more specific cell subsets may potentially be markers associated with disease relapse [37]. We showed that changes in plasma cells were strongly correlated with the reactivation of CNS disease.…”

Section: Discussionmentioning

confidence: 71%

Longitudinal immune cell monitoring identified CD14++ CD16+ intermediate monocyte as a marker of relapse in patients with ANCA-associated vasculitis

et al. 2020

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Background: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an autoimmune disease that affects small-to medium-sized blood vessels. Despite treatments having been improved, patients often experience disease relapses. It remains unclear how the immune cells involve in the development of vasculitis and how they fluctuate over the course of treatment. In this study, we aimed to identify the immune subsets and serum cytokines associated with disease relapse by comprehensive immuno-phenotyping in AAV patients. Methods: We reviewed consecutive patients (n = 29) from Keio University Hospital who had been newly diagnosed with AAV from January 2015 to February 2019 and chronologically followed until 52 weeks. Numbers of circulating T cells, B cells, monocytes, and granulocytes were analyzed by flow cytometry (FACS). Serum levels of cytokines were measured by electrochemiluminescence enzyme immunoassay. Clinical information was obtained from patients' records and association with time-course changes in immuno-phenotypes and serum levels of cytokines were assessed. Results: Comprehensive immuno-phenotyping data from 161 samples from 29 AAV patients at diagnosis; at weeks 4, 12, 24, and 52 of treatment; and at time of major relapse were examined. FACS analysis from patients with relapse revealed that CD14 ++ CD16 + intermediate monocytes and plasma cells concomitantly changed associated with disease relapse, which were independent from treatment regimen, ANCA status, or disease phenotype. In particular, the number of CD14 ++ CD16 + intermediate monocytes at relapse was significantly higher than that in remission or in healthy controls. Serum cytokine measurement revealed that changes of monocyte-derived proinflammatory cytokines such as IL-1β, IL-6, IL-8, and TNF-α were associated with disease status. Conclusions: Chronological changes in CD14 ++ CD16 + intermediate monocyte counts can be a marker of disease relapse in AAV patients.

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“…Persistent positive-ANCAs (22), CD27-CD38hi B-cell frequency (23) and non-standardized glucocorticoid therapy are key risk factors for a poor prognosis. Although endobronchial involvement may improve symptoms, further studies are required to investigate whether the incomplete excision of the lesion can cause a relapse of the existing granulomata development (24).…”

Section: Discussionmentioning

confidence: 99%

Main tract stenosis complicated by granulomatous with polyangiitis: A case report

Zhou

Zhang

et al. 2020

Exp Ther Med

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Granulomatosis with polyangiitis (GPA) is a rheumatic auto-immune disease involved in vasculitis. It is rarely reported that anti-neutrophil cytoplasmic antibodies (ANCAs) associated with GPA would cause main tract stenosis. The current report documents a 54-year-old woman, with a history of severe cough, presented with wheezing and shortness of breath. Although she was treated with cephalosporin antibiotics for half a month, the symptoms were not alleviated. Accordingly, laboratory testing, radiology and pathology was performed at the Department of Respiratory and Critical Care Medicine, Huashan Hospital. Blood samples were tested negative for ANCAs. Chest CT revealed stenosis of the main trachea and uneven thickening of the tracheal wall. Nasal sinuses CT scanning indicated thickening of the nasal mucosa. Pathological analysis demonstrated chronic granulomatous inflammation with focal lesions. According to the classification criteria of ACR/EULAR provisional 2017, the patient was diagnosed with the ANCAs-negative GPA. Following treatment with oral prednisone only for 6 months, obstruction of main tract was significantly improved. This case study is of interest for the promotion a potentially novel therapeutic intervention for GPA associated with the absence ANCA of in clinic.

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CD27+CD38hi B Cell Frequency During Remission Predicts Relapsing Disease in Granulomatosis With Polyangiitis Patients

Cited by 32 publications

References 37 publications

ANCA-associated vasculitis

ANCA-associated vasculitis

Longitudinal immune cell monitoring identified CD14++ CD16+ intermediate monocyte as a marker of relapse in patients with ANCA-associated vasculitis

Main tract stenosis complicated by granulomatous with polyangiitis: A case report

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