• Fri. Nov 15th, 2024

Older age, delayed initial improvement after immunotherapy, and respiratory failure may be associated with poor outcomes

Byacusticavisual

Oct 3, 2024

Older age, delayed initial improvement after immunotherapy, and respiratory failure may be associated with poor outcomes. strong class=”kwd-title” Keywords: GABABR encephalitis, immunotherapy, tumour treatment, CD19+B cell percentage, prognosis Introduction Since the discovery of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in 2007,1 a series of autoantibodies against neuronal cell surface or synaptic proteins, such as anti-leucine-rich glial inactivating protein 1 (LGI-1) antibodies and AS-1517499 anti–aminobutyric acid B (GABAB) receptor antibodies, have been discovered in succession.2 In contrast to the classic paraneoplastic neurological syndrome, B cell-based humoral immunity plays an important role in the pathogenesis. Small-cell AS-1517499 lung cancer was detected in twelve patients. Among the patients who died because of tumours, patients who received tumour treatment lived longer than patients who did not receive tumour treatment (P=0.025). All four surviving patients who received tumour treatment had good outcomes (mRS2). The median serum CD19+B cell percentage in sixteen patients were 20.00% and 13.42% prior first-line immunotherapy and at the last follow-up (P 0.01). After a maximum follow-up of 54 months (median: 12; range: 3C54), eleven patients (55%) had a poor prognosis (mRS 2). Predictors of a poor prognosis were older age (P=0.031), delayed initial improvement after immunotherapy ( 4 weeks) (P=0.038) and respiratory failure (P=0.038). Conclusion Aggressive immunotherapy and tumour treatment contribute to improvements in neurological function and a better prognosis of patients with GABABR encephalitis. The serum CD19+B cell percentage may be an indicator of disease activity. Older age, delayed initial improvement after immunotherapy, and respiratory failure may be associated with poor outcomes. strong class=”kwd-title” Keywords: GABABR encephalitis, immunotherapy, tumour treatment, CD19+B cell percentage, prognosis Introduction Since the discovery of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in 2007,1 a series of autoantibodies against neuronal cell surface or synaptic proteins, such as anti-leucine-rich glial inactivating protein 1 (LGI-1) antibodies and anti–aminobutyric acid B (GABAB) receptor antibodies, have been discovered in succession.2 In contrast to the classic paraneoplastic neurological syndrome, B cell-based humoral immunity plays an important role in the pathogenesis. Due to the pathogenic effects of specific antibodies, patients respond well to immunotherapy.3 GABAB receptors (GABABRs) are G protein-coupled receptors involved in the regulation of glutamate signalling and play an important role in neurotransmitter transmission and synaptic AS-1517499 stability.4 GABABR encephalitis was first reported in 2010 2010. 5 These antibodies have a mode of action similar to the NMDAR antibodies by altering the receptor density, and clinical manifestations are similar to NMDAR encephalitis, with prominent cognitive decline, memory problems, psychotic episodes and seizures. Patients with GABABR encephalitis have also been reported to develop coexisting (or overlapping) autoantibodies, such as antibodies targeting voltage-gated calcium channels (VGCCs), glutamic acid decarboxylase 65 (GAD65), and sex determining region Y-box 1 (SOX1).6,7 Approximately 50% of patients have tumours, 92% of which are small-cell lung cancer (SCLC).8 The five-year survival rate of patients with SCLC is less than 10%,9 which affects the prognosis of patients. Due to the rarity of this disease, few studies have focused on it, and the understanding of this disease is limited. This retrospective study aimed to examine the effects of immunotherapy and tumour treatment on patients with GABABR encephalitis, to determine the percentage of serum lymphocytes at different stages of the disease, and to identify factors related to disease prognosis. Methods AS-1517499 Patients Study cases came from a series of 624 patients who presented to the Provincial Hospital Affiliated to Shandong University from December 2015 to April 2020. The patients included fulfilled the following criteria in the study:10 (1) acute or subacute onset ( 3 months); (2) symptomatic manifestations of encephalitis; (3) GABABR antibody positivity in serum and/or cerebrospinal fluid (CSF); and (4) no intracranial infectious, traumatic, toxic, metabolic, intracranial neoplastic or demyelinating diseases. All patients were tested for cell surface antigen antibodies against the GABAB receptor, NMDA receptor, AMPA receptor, LGI1 and CASPR2 receptor by cell-based assay (CBA) on human embryonic kidney (HEK 293) cells transfected with plasmids in serum and CSF. Classic paraneoplastic autoantibodies (anti-Hu, -Yo, -Ri, -CV2/CRMP5, -amphiphysin and -Ma2/Ta) were also detected by immunoblot assay in serum. All samples were sent to EUROIMMUN Medical Diagnostics in Hangzhou, China for testing. The study was approved by the Research Ethics Committee of Shandong Provincial Hospital Affiliated to Shandong University. Assessment of Clinical Information The demographic characteristics, clinical manifestations, results of auxiliary examinations, treatment strategies and prognosis were collected by professional neurologists through a review of data collected during hospitalization and telephone and outpatient follow-up. All patients were analysed using continuous electroencephalography (EEG) monitoring (24 h), brain magnetic resonance imaging (MRI) and CSF assays. Contrast-enhanced computed tomography (CT) was performed to assess the presence of Rabbit Polyclonal to WIPF1 tumours. GABABR antibody titres were categorized as weakly positive ( 1:10), positive ( 1:100) and strongly positive (1:100). Treatment and Follow-Up Patients received first-line immunotherapy,.