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52. Humoral and Cellular Immune Responses to SARS-CoV-2 mRNA Vaccination in Patients with Multiple Sclerosis: An Israeli Multi-Center Experience Following 3 Vaccine Doses.

Author

Milo, Ron, Staun-Ram, Elsebeth, Karussis, Dimitrios, Karni, Arnon, Hellmann, Mark A., Bar-Haim, Erez, Miller, Ariel, Glass-Marmor, Lea, Volkovitz, Anat, Dishon, Sara, Dishon, Zeev, Kugelman, Netta, Nitsan, Zeev, Alkrenawi, Marwan, Hovel, Nurit, Michal, Nir, Loew-Shavit, Vered, Mizrahi, Lital, Zafrani, Marsel, and Petrou, Panayiota

Subjects
HUMORAL immunity, FINGOLIMOD, MULTIPLE sclerosis, VACCINATION, SARS-CoV-2, MESSENGER RNA, COVID-19 vaccines
Abstract

Background: Immunomodulatory/immunosuppressive activity of multiple sclerosis (MS) disease modifying therapies (DMTs) might affect immune responses to SARS-CoV-2 exposure or vaccination in patients with MS (PwMS). We evaluated the effect of DMTs on humoral and cell-mediated immune responses to 2 and 3 vaccinations and the longevity of SARS-Cov-2 IgG levels in PwMS. Methods: 522 PwMS and 68 healthy controls vaccinated with BNT162b2-Pfizer mRNA vaccine against SARS-CoV-2, or recovering from COVID-19, were recruited in a nation-wide multi-center study. Blood was collected at 3 time-points: 2-16 weeks and ~6 months post 2nd vaccination and 1-16 weeks following 3rd vaccination. Serological responses were measured by quantifying IgG levels against the spike-receptor-binding-domain of SARS-CoV-2, and cellular responses (in a subgroup analysis) by quantifying IFNγ secretion in blood incubated with COVID-19 spike-antigen. Results: 75% PwMS were seropositive post 2nd or 3rd vaccination. IgG levels decreased by 82% within 6 months from vaccination (p<0.0001), but were boosted 10.3 fold by the 3rd vaccination (p<0.0001), and 1.8 fold compared to ≤3m post 2nd vaccination (p=0.025). Patients treated with most DMTs were seropositive post 2nd and 3rd vaccinations, however only 38% and 44% of ocrelizumab-treated patients and 54% and 46% of fingolimod-treated patients, respectively, were seropositive. Similarly, in COVID-19-recovered patients only 54% of ocrelizumab-treated, 75% of fingolimod-treated and 67% of cladribine-treated patients were seropositive. A time interval of ≥5 months between ocrelizumab infusion and vaccination was associated with higher IgG levels (p=0.039 post-2nd vaccination; p=0.036 post-3rd vaccination), and with higher proportions of seropositive patients. Most fingolimod- and ocrelizumab-treated patients responded similarly to 2nd and 3rd vaccination. IFNγ-T-cell responses were detected in 89% and 63% of PwMS post 2nd and 3rd vaccination, however in only 25% and 0% of fingolimod-treated patients, while in 100% and 86% of ocrelizumab-treated patients, respectively. Conclusion: PwMS treated with most DMTs developed humoral and T-cell responses following 2 and 3 mRNA SARS-CoV-2 vaccinations. Fingolimod- or ocrelizumab-treated patients had diminished humoral responses, and fingolimod compromised the cellular responses, with no improvement after a 3rd booster. Vaccination following >5 months since ocrelizumab infusion was associated with better sero-positivity. These findings may contribute to the development of treatment-stratified vaccination guidelines for PwMS. [ABSTRACT FROM AUTHOR]

Published
2022
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57. Glatiramer Acetate Depot (extended-release) phase IIa study in patients with relapsing remitting multiple sclerosis: safety, tolerability and efficacy (No Evidence of Disease Activity) subpopulation three-years analysis (1936)

Author

Flechter, Shlomo, primary, Miller, Ariel, additional, Popper, Laura, additional, Kimelman, Nadav Bleich, additional, Rubnov, Shai, additional, Danon, Uri, additional, Marom, Ehud, additional, Milo, Ron, additional, Chapman, Joab, additional, Shifrin, Alla, additional, Gilad, Ronit, additional, Hoffmann, Chen, additional, Karussis, Dimitrios, additional, and Karni, Arnon, additional

Published
2020
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58. Glatiramer Acetate Depot (extended-release) phase IIa study in patients with primary progressive multiple sclerosis: safety and efficacy snapshot (1956)

Author

Flechter, Shlomo, primary, Popper, Laura, additional, Kimelman, Nadav Bleich, additional, Demender, Inna, additional, Rubnov, Shai, additional, Danon, Uri, additional, Marom, Ehud, additional, Milo, Ron, additional, Gilad, Ronit, additional, Weller, Boaz, additional, Vaknin-Dembinsky, Adi, additional, Hellmann, Mark, additional, and Karni, Arnon, additional

Published
2020
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63. Susac’s syndrome – A new ocular finding and disease outcome

Author

Zur, Dinah, Goldstein, Michaella, Barequet, Dana, Oron, Yahav, Elkayam, Ori, Karni, Arnon, Wilf-Yarkoni, Adi, Regev, Keren, and Habot-Wilner, Zohar

Abstract

Background: Susac’s syndrome, a rare autoimmune vasculo-occlusive disease, may pose a diagnostic challenge and result in a devastating ocular and systemic outcome. Our study identifies a new retinal finding and evaluates disease outcome. We aimed to assess clinical and imaging findings, systemic manifestations and disease outcome in patients with ocular Susac’s syndrome under immunosuppressive/immunomodulation therapies. Methods: Retrospective tertiary center study including patients with a diagnosis of Susac’s syndrome with >12 months follow up. Medical record review including ocular, neurological and auditory clinical and imaging findings, and treatment modalities. Main outcome measures were clinical manifestations and disease outcome. Results: Seven patients (14 eyes) with a mean age of 34.1 years were included. Mean follow-up was 31.9 months (12.4–72.4). All had bilateral ocular disease. Retinal microaneurysms, a new ocular finding, were demonstrated in 5 patients and persisted at the final visit. In 5 eyes, they further extended during follow-up. All were treated with immunosuppressive drugs and 5/7 additional immunomodulation therapy. At last examination, best corrected visual acuity was >20/40 in all eyes, 1/10 eyes had visual field deterioration, no eye had active ocular disease, all patients achieved neurological stability, and 1 patient had auditory deterioration. Conclusion: Retinal microaneurysms, a new ocular finding in Susac’s syndrome, were present in most of our patients, indicating ischemic retinal damage. Immunosuppressive and immunomodulation therapies seem to be highly effective in the control of disease activity.

Published
2022
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66. Glatiramer Acetate Depot (Extended-Release) Phase IIa Study in Patients with Relapsing Remitting Multiple Sclerosis: Safety, Tolerability and Efficacy (No Evidence of Disease Activity) Two-Years Analysis (P3.2-052)

Author

Flechter, Shlomo, primary, Miller, Ariel, additional, Popper, Laura, additional, Kimelman, Nadav Bleich, additional, Rubnov, Shai, additional, Danon, Uri, additional, Marom, Ehud, additional, Milo, Ron, additional, Chapman, Joab, additional, Shifrin, Alla, additional, Gilad, Ronit, additional, Hoffmann, Chen, additional, Karussis, Dimitrios, additional, and Karni, Arnon, additional

Published
2019
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73. Glatiramer Acetate Depot (extended-release) Phase IIa one-year study in patients with Relapsing-remitting Multiple Sclerosis: Safety, tolerability and efficacy – NEDA Analysis (P6.359)

Author

Miller, Ariel, primary, Popper, Laura, additional, Danon, Uri, additional, Kimelman, Nadav Bleich, additional, Rubnov, Shai, additional, Marom, Ehud, additional, Chapman, Joab, additional, Shifrin, Alla, additional, Gilad, Ronit, additional, Karussis, Dimitrios, additional, Milo, Ron, additional, Hoffmann, Chen, additional, Flechter, Shlomo, additional, and Karni, Arnon, additional

Published
2018
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80. A tri-modal distribution of age-of-onset in female patients with myasthenia gravis is associated with the gender-related clinical differences.

Author

Asmail, Ali, Kesler, Anat, Kolb, Hadar, Drory, Vivian E., and Karni, Arnon

Subjects
MYASTHENIA gravis, WOMEN patients
Abstract

Background: A tri-modal distribution of age-at-onset emerged among females patients with myasthenia gravis (MG) in our database. This finding may be indicative of different gender-based disease mechanisms. Methods: We retrospectively reviewed the files of 127 MG patients for the clinical, serology and thymus pathology according to their age at disease onset: ≤40 years (early-onset, EOMG), 40-70 years (intermediate-onset, IOMG) and >70 years (late-onset, LOMG). Results: EOMG was more common among females, and IOMG was more common among males. Ocular MG was more common among the male MG patients with an IOMG. Patients with EOMG had lower rates of positive anti-acetylcholine receptor (anti-AChR). IOMG females, but not IOMG males, had lower rates of positive anti-AChR. IOMG and EOMG females had high rates of thymic hyperplasia, while EOMG males had high rates of thymoma. Comorbidity with autoimmune diseases was common among females with IOMG and LOMG. Conclusions: The prevalence of IOMG was the reason for the trend reversal of MG prevalence between genders. The clinical features of patients with IOMG differed between genders in the rates of positive anti-AChR, follicular hyperplasia of the thymus and comorbidity with autoimmune diseases. This may suggest a different gender-based mechanism of immune intolerance towards AChR and other antigens. [ABSTRACT FROM AUTHOR]

Published
2019
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89. Teaching NeuroImages: Hypertrophic olivary degeneration in a young man with POLGgene mutation

Author

Arkadir, David, Meiner, Vardiella, Karni, Arnon, and Lossos, Alexander

Abstract

A 30-year-old man with sensorineural hearing loss presented with subacute somnolence, slurred speech, and unsteady gait following treatment with peginterferon α-2b and ribavirin for chronic hepatitis C virus. Examination revealed scanning speech, horizontal nystagmus, gait ataxia, and symmetric hyporeflexia with distal sensory loss. There was no palatal myoclonus. Metabolic and serologic workup and blood lactate were unrevealing. Brain MRI demonstrated bilateral hypertrophic olivary degeneration (HOD, figure). Whole exome sequencing identified a homozygous pathogenic p.W748S POLGmutation.1Differential diagnosis of bilateral HOD includes mutations in the nuclear genes crucial to mitochondrial function, POLGand SURF1.2

Published
2023
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95. Increased anti-KIR4.1 antibodies in multiple sclerosis: Could it be a marker of disease relapse?

Author

Brill, Livnat, Goldberg, Lotem, Karni, Arnon, Petrou, Panayiota, Abramsky, Oded, Ovadia, Haim, Ben-Hur, Tamir, Karussis, Dimitrios, and Vaknin-Dembinsky, Adi

Subjects
THERAPEUTIC use of immunoglobulins, NEUROMYELITIS optica, MULTIPLE sclerosis treatment, MYELIN sheath diseases, MEDICAL care, THERAPEUTICS
Abstract

The article examines the anti-KIR4.1 antibodies in the serum of patients with neuromyelitis optica (NMO) and multiple sclerosis (MS). The study indicates the high anti-KIR4.1 antibodies serum levels in MS and NMO patients when compared to those in healthy controls. It points out that the antibodies do not discriminate between the demyelinating diseases.

Published
2015
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