ABSTRACT
Objective To report a case of Anti-Contactin-Associated Protein-like2 (CASPR-2) autoimmunity in a patient with low-grade Chronic Lymphocytic Leukemia (CLL) following COVID-19 vaccination and infection. Background Anti-CASPR2 antibody disorder has been associated with neoplastic disorders like thymoma. Recent reports enlist COVID-19 as apotential trigger of CASPR2 autoimmunity. While the clinical presentations are similar, management differs based on the underlying etiology. Design/Methods We review a case of anti-CASPR2-antibody associated disorder with concurrent low grade CLL and recent history of COVID-19 vaccination and infection. Additionally, we review the literature and discuss the therapeutic challenges. Results A 73-years old male presented with five months of progressive fatigue, weight loss, diffuse sweating, muscle cramps, and neuropathic pain. He eventually developed bilateral upper and lower facial weakness. Patient contracted a mild COVID-19 infection two months prior and COVID- 19 vaccination one month prior to his symptom onset. His exam was remarkable for bilateral facial weakness, diffuse fasciculations and sensory neuropathy on his trunk and extremities. His diagnostic work up including bone marrow biopsy was consistent with a chronic lymphocytic leukemia (CLL)-like immunophenotype. Cerebrospinal fluid (CSF) analysis was remarkable for five WBC (lymph-dominant) and protein of 74 mg/dl. Serum paraneoplastic panel revealed positive CASPR2 antibody with a titer of 1:100. Magnetic Resonance Imaging (MRI) of the brain showed enhancement of bilateral cranial nerve VII. After lack of clinical response to IV methylprednisone (1 gram for 5 days), patient was treated with a single cycle of IV immunoglobulin (IVIG). He had complete recovery of his symptoms except for residual facial weakness. He remains stable at his six months post-treatment follow-up. Conclusions Anti-CASPR2 associated autoimmunity following COVID-19 infection or in the setting of CLL has previously been reported. However, cranial neuropathy in association with CASPR2 antibody has never been. A trial of IVIG could be beneficial in patients with viral-spike protein-induced autoimmunity and CLL who do not otherwise meet the criteria for CLL treatment.
ABSTRACT
Objective: To expand understanding of the human immunological response to SARS-CoV-2 vaccination in patients with Multiple Sclerosis (MS) treated with anti-CD20 monoclonal therapy and sphingosine-1-phosphate (S1P) modulators. Background: Immunomodulatory therapy prescribed for patients with MS has been associated with decreased or absent anti-SARS-CoV-2 immunoglobulin production following COVID-19 vaccination. We investigate broader adaptive immune responses to SARS-CoV-2 vaccination measuring IgG immunoglobulin production and T-cell reactivity in a small cohort. Design/Methods: We used the Stanford Research Repository database to identify 55 MS patients by ICD10 code who were tested for B-cell and T-cell responses via SARS-CoV-2-IgG and SARS-CoV-2 Interferon Gamma Release Assay (IGRA), respectively. 96% (53/55) of patients were fully vaccinated (98% mRNA/2% Janssen). A Chi-square test compared differences in vaccine response between 3 different disease modifying treatment (DMT) groups: anti-CD20 therapy (n=24), S1P modulators (n=11), and off DMT/other MS therapies (n=20). Results: In patients on anti-CD20 therapy, 71% (17/24) were positive for SARS-CoV-2 IGRA but negative for SARS-CoV-2 IgG, among which 65% (11/17) had low CD-19 levels (0-64 cells/uL, normal 100-500 cells/uL) with normal absolute lymphocyte count (ALC). Among patients who delayed vaccination by 4-6 months following anti-CD20 therapy, 13% (3/24) expressed SARS-CoV-2-IgG. 82% (9/11) of patients on S1P modulators showed absent SARS-CoV-2-IgG and SARS-CoV-2 IGRA responses, in association with low ALC (range 210-600 cells/uL, normal 1000-3000 cells/uL). 95% (19/20) of patients off DMT/on other MS therapies showed positive SARS-CoV-2-IgG and SARS-CoV-2 IRGA responses. All vaccinated patients were assessed between 4 weeks and 6 months post-vaccination. These differential responses between treatment groups were significant (p<0.05). Conclusions: We demonstrate that among MS patients treated with anti-CD20 therapy, T-cell response was largely preserved despite greatly reduced B-cell response to SARS-CoV-2 vaccination. MS patients on S1P modulators demonstrated absence of both B-cell and T-cell response. The clinical correlation of this is to be determined.