Anti-factor VIII (FVIII) antibody development poses a significant challenge in hemophilia A (HA) patients receiving FVIII protein replacement therapy. There is an urgent need for novel therapeutic strategies to inhibit the production of anti-FVIII inhibitory antibodies (inhibitors) in HA. This study aimed to investigate a combination monoclonal antibody (mAb) therapy targeting CXCL13 and CD20 on the development of anti-FVIII antibodies in a HA murine model, along with the underlying mechanisms involved. Specifically, mAbs targeting mouse CD20 (18B12) with an IgG2a backbone and mouse CXCL13 (2C4) with an IgG1 backbone were synthesized. HA mice with FVIII inhibitors were established, and the results revealed that the combination therapy of anti-mCD20 with α-mCXCL13 significantly suppressed anti-FVIII antibody development and induced FVIII tolerance. Furthermore, this combination therapy led to a marked reduction of peripheral and splenic follicular helper T cells and an enhancement of regulatory T cell induction, along with sustained depletion of bone marrow and splenic plasma cells in HA mice with preexisting FVIII immunity. Thus, the concurrence of blockage of CD20 and neutralization of CXCL13 hold promise as a therapeutic strategy for HA patients with inhibitors.

2024-07-26·Medicine

Coexistence of double seropositivity for MPO antibody and anti-GBM antibody in ANCA-associated vasculitis concurrent with multiple myeloma: A case report

Article

作者: Han, Seungyeup ; Choe, Misun ; Yang, Jaeseok ; Kim, Yaerim ; Lee, Hyeonjeong ; Kwon, Jinykung ; Shin, Hyeongchan ; Heo, Mihwa ; Jin, Kyubok ; Paek, Jin Hyuk

Rationale:Immune-mediated vasculitis with 2 or more autoantibodies, for example, anti-proteinase-3, combined with anti-myeloperoxidase (MPO) or anti-glomerular basement membrane (GBM) antibodies, is extremely unusual. Furthermore, the coexistence of autoimmune vasculitis and hematological malignancies is uncommon. Herein, we describe a case of double-seropositive anti-neutrophil cytoplasmic antibody (ANCA) vasculitis with multiple myeloma.Patient concerns:A 79-year-old Asian man presented with persistent leg edema and kidney dysfunction. His kidney function rapidly decreased, and serologic test results showed higher titers of the anti-MPO antibody (54.7 IU/mL) and anti-GBM antibodies (>200 IU/mL). Additionally, the clinical features showed the possibility of monoclonal gammopathy with anemia and hyperglobulinemia. We performed kidney and bone marrow biopsy. Serum protein electrophoresis and immunofixation revealed no significant differences, but the results of the bone marrow smear were compatible with those of myeloma with 15% plasmacytosis. However, kidney biopsy showed diffuse crescentic glomerulonephritis without deposition of the immune complex or kappa/lambda chain.Diagnoses and Interventions:Finally, the patient was diagnosed with double-seropositive ANCA-associated glomerulonephritis and multiple myeloma. Given the patient’s performance status, we initiated low-dose steroid pulse therapy, followed by conservative management.Outcomes:While the pulmonary lesions showed improvement, the kidney function did not regain its previous state, prompting the initiation of kidney replacement therapy by hemodialysis. There has been a decrease in the levels of anti-GBM and anti-MPO antibodies since the initial diagnosis.Lessons:This case elucidates the complex interplay between ANCA-associated glomerulonephritis and hematologic malignancy and emphasizes the need for a nuanced treatment strategy considering its multifaceted clinical presentation.

2023-12-12·Annals of Medicine

Application of thyroglobulin and anti-thyroglobulin antibody combined with emission computed tomography in the adjuvant diagnosis of differentiated thyroid carcinoma

Article

作者: Li, Jialong ; Li, Yungeng ; Zhang, Laney ; Lin, Chenghe ; Jiao, Benzheng ; Jiang, Nan

PURPOSEThyroid nodules are a kind of common endocrine system disease, with approximately 5% of them developing into malignant lesions, the most common of which belong to differentiated thyroid carcinoma (DTC). Accurate differential diagnosis using reliable methods and targeted treatment of benign and malignant thyroid nodules are of great significance to improve patient outcomes. This study mainly investigates the diagnostic value of thyroglobulin (Tg) and anti-thyroglobulin antibody (anti-TgAb) combined with emission computed tomography (ECT) in the adjuvant diagnosis DTC.METHODSAll the data of 387 histopathologically diagnosed DTC patients (observation group) and 151 patients with nodular goiter (control group) admitted between June 2019 and June 2021 were collected and retrospectively analyzed. Serum Tg and anti-TgAb levels were detected in all subjects. In addition, all patients in the observation group underwent thyroid ECT, and the results were compared with the pathological findings. The receiver operating characteristic (ROC) curve was drawn to analyze the diagnostic performance of Tg, TgAb and thyroid ECT, either alone or in combination, in patients with thyroid cancer (TC).RESULTSThe consistency test showed that Tg (Kappa-value = 0.370) and anti-TgAb (Kappa-value = 0.393) had generally consistent efficiency with pathological findings in the diagnosis of DTC; ECT (Kappa-value = 0.625) and the combined diagnosis of the three (Kappa-value = 0.757) showed higher consistency than the pathological diagnosis, of which the combined diagnosis contributed to an even higher consistency. The combined diagnosis of Tg, anti-TgAb, and thyroid ECT outperformed either of these alone in DTC diagnosis, with a sensitivity of 91.5%, a specificity of 86.1%, and an accuracy of 90%.CONCLUSIONSThe combination of Tg. anti-TgAb, and RNI can effectively improve the diagnostic accuracy of DTC and reduce the missed diagnosis rate, which has important reference significance for clinical diagnosis and treatment of TC.

项与 Anti-Hemophilia Antibody ( Beijing Neoletix Biological ) 相关的新闻（医药）

2023-05-30

·EndPoints

Pfizer’s once-a-week hemophilia antibody reduces bleeding in PhIII study

Pfizer’s once-a-week antibody treatment for hemophilia A and B helped reduce bleeding events in patients compared to their usual treatment of blood clotting factor infusions, the pharma company announced Tuesday morning. The open-label Phase III study included 116 people with hemophilia who were first treated for six months with either regular or on-demand infusions of factor VIII or IX — the clotting factors that patients with hemophilia A and B are missing. Then, both groups switched over to once-a-week treatment with Pfizer’s antibody marstacimab for one year. Unlock this article along with other benefits by subscribing to one of our paid plans.