Retrospective analysis of efgartigimod use in patients with double-seronegative generalized myasthenia gravis: a case series.

The effect of treatment with efgartigimod in seronegative myasthenia gravis (MG) remains unclear. This retrospective study aimed to evaluate symptomatic changes and safety of treatment with efgartigimod in patients with generalized MG (gMG) double-seronegative for acetylcholine receptor antibody and muscle-specific kinase antibody. We reviewed the medical records of double-seronegative gMG treated with 10 mg/kg efgartigimod once/week per cycle (4 weeks) from June 2022 to June 2023. A total of 16 patients were included. MG-activities of daily living (ADL) scores improved from 9.2 to 7.4. Mean prednisolone dose was reduced from 5.4 to 4.1 mg/day. The duration before MG-ADL deterioration after the end of a cycle was 6.1 weeks. Five patients had mild adverse events. This retrospective study revealed no significant treatment benefit in the outcomes of patients with double-seronegative gMG treated with efgartigimod.

[A case of Stiff-person syndrome with muscle tonicity of the extremities and neck after use of Dulvalumab for lung adenocarcinoma].

A 74-year-old woman taking dulvalumab for lung adenocarcinoma developed muscle tonicity in the extremities and trunk. Painful paroxysmal muscle spasms with profuse sweating were frequently observed, and surface electromyography showed simultaneous contraction of the active and antagonist muscles. Blood tests were strongly positive for anti-amphiphysin antibodies, and stiff-person syndrome (SPS) was diagnosed. Intravenous immunoglobulin therapy and clonazepam were initiated, and the paroxysmal painful muscle spasms disappeared. As the primary tumor was under control, and the onset occurred approximately six weeks after the resumption of immune checkpoint inhibitors, we considered SPS to be an immune-related adverse event. Although extremely rare, it should be considered a neuromuscular disease that can occur in association with immune checkpoint inhibitors.

[A Case of Bing-Neel Syndrome With Repeated Long Spinal Cord Lesions].

The patient was a 45-year-old man. Since 2019, he had exhibited repeated steroid-improved dysuria and long spinal cord lesions. At the time of recurrence in June 2020, he exhibited a marked increase in serum IgM levels, suggesting hematopoietic disease. We found an MYD88 L265P mutation in cerebrospinal fluid cells, which subsequently led to the diagnosis of Bing-Neel syndrome (BNS). The patient was treated with Burton's tyrosine kinase inhibitors and his condition progressed without dysuria or worsening of the imaging findings. This case was challenging to differentiate from intractable inflammatory diseases; however, the identification of hyper-IgM helped in the diagnosis. BNS should be differentiated from central nervous system lesions through the identification of hyper-IgM.

Smoking and younger age at onset in anti-acetylcholine receptor antibody-positive myasthenia gravis.

Smoking is a known risk factor for the development and progression of several autoimmune diseases. Previous studies have pointed out the association of smoking with the development and worsening of symptoms in myasthenia gravis (MG), but further investigation is necessary to confirm this association. Smoking history was investigated in a cross-sectional study of 139 patients with anti-acetylcholine receptor antibody-positive MG, and the association of smoking history with the age at the onset of MG was analyzed. Patients who had been smoking at the onset of MG were significantly younger compared with those who had never smoked or had quit before the onset of MG. A linear regression analysis adjusting for sex and the presence/absence of thymoma showed a significant association between smoking at onset and younger age at onset (regression coefficient -9.05; 95% confidence interval, -17.6, -0.51; p = 0.039). Among patients with smoking exposure within 10 years prior to or at the onset of MG, women were significantly younger at the onset of MG compared with men. Our results suggest that smoking is an independent risk factor for the earlier development of anti-acetylcholine receptor antibody-positive MG and further support the putative link between smoking and MG.

Molecular design of glycoprotein mimetics: glycoblotting by engineered proteins with an oxylamino-functionalized amino acid residue.

The general and efficient method for the site-directed glycosylation of proteins is a key step in order to understand the biological importance of the carbohydrate chains of proteins and to control functional roles of the engineered glycoproteins in terms of the development of improved glycoprotein therapeutics. We have developed a novel method for site-directed glycosylation of proteins based on chemoselective blotting of common reducing sugars by genetically encoded proteins. The oxylamino-functionalized L-homoserine residues, 2-amino-4-O-(N-methylaminooxy) butanoic acid and 2-amino-4-aminooxy butanoic acid, were efficiently incorporated into proteins by using the four-base codon/anticodon pair strategy in Escherichia coli in vitro translation. Direct and chemoselective coupling between unmodified simple sugars and N-methylaminooxy group displayed on the engineered streptavidin allowed for the combinatorial synthesis of novel glycoprotein mimetics.