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Humoral and cellular responses to SARS-CoV-2 vaccination in patients with autoantibody-mediated neuroimmunology
  1. Keigo Kihara1,
  2. Makoto Kinoshita1,
  3. Tomoyuki Sugimoto2,
  4. Shuhei Okazaki1,
  5. Hisashi Murata1,
  6. Shohei Beppu1,
  7. Naoyuki Shiraishi1,
  8. Yasuko Sugiyama1,
  9. Toru Koda1,
  10. Tatsusada Okuno1,
  11. Hideki Mochizuki1
  1. 1 Department of Neurology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
  2. 2 Graduate School of Data Science, Shiga University, Hikone, Shiga, Japan
  1. Correspondence to Dr Makoto Kinoshita, Department of Neurology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan; mkinoshita{at}; Dr Tatsusada Okuno, Department of Neurology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan; okuno{at}

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COVID-19 caused by SARS-CoV-2 is still prevalent worldwide. In Japan, two types of mRNA vaccines, BNT162b2 and mRNA-1273, have been widely administered. Neuromyelitis optica spectrum disorder (NMOSD) and myasthenia gravis (MG) are representative autoantibody-mediated neuroimmunological diseases. Majority of the patients are required to take immunosuppressive medication. In this regard, there is an urgent need to clarify the immune responses elicited by SARS-CoV-2 mRNA vaccination to elucidate its efficacy and the potential immune flare in these patients. Insufficient humoral immune responses and potent SARS-CoV-2 spike (S)-specific CD4+ T-cell responses were shown in patients with NMOSD. Alteration of follicular helper T (Tfh) cell phenotype may attenuate the production of anti-S antibody and indicate potential risk of immune flare of the disease activity.


Demographic and clinical characteristics of the patients were shown in online supplemental table 1. One patient in each of NMOSD and MG groups developed COVID-19 within 6 months after the first vaccination. No COVID-19 case was recorded in controls. In the NMOSD group, recurrence was observed in one patient (5%) by 1 month after the second vaccination.

Supplemental material


Anti-S IgG titre was significantly lower in patients with NMOSD and MG compared with controls (figure 1A). SARS-CoV-2 S-receptor binding domain (RBD)-specific ratio in B cells increased after vaccination only in controls (online supplemental figure 1A). When NMOSD and MG cohorts were categorised by treatment regimens, significant reduction in anti-S IgG titre was observed in patients receiving prednisolone as well as prednisolone and tacrolimus combination therapy (figure 1B). Significant negative correlation was found between the dose of prednisolone and anti-S IgG titre (Spearman’s rank, r=−0.396, p=0.033).

Figure 1

Anti-SARS-CoV-2 S-IgG response after the second dose of vaccination in the control, NMOSD and MG groups (A). Anti-SARS-CoV-2 S-IgG response after the …

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  • KK and MK contributed equally.

  • Contributors KK and MK contributed to the conception and design of the study. KK, MK, SO, HM, SB, NS, YS and TK contributed to the acquisition and analysis of data. TS performed part of the statistical analysis. KK and MK contributed to drafting the manuscript and preparing the figures. TO and HM helped supervise the project and interpreted the data.

  • Funding This work was supported by JSPS KAKENHI, grant numbers JP20K07759 and JP18H05282.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.