Postvaccination anti-S IgG levels predict anti-SARS-CoV-2 neutralising activity over 24 weeks in patients with RA

OBJECTIVES To correlate immune responses following a two-dose regimen of mRNA anti-SARS-CoV-2 vaccines in patients with rheumatoid arthritis (RA) to the development of a potent neutralising antiviral activity. METHODS The RECOVER study was a prospective, monocentric study including patients with RA and healthy controls (HCs). Assessments were performed before, and 3, 6, 12 and 24 weeks, after the first vaccine dose, respectively, and included IgG, IgA and IgM responses (against receptor binding domain, S1, S2, N), IFN-γ ELISpots as well as neutralisation assays. RESULTS In patients with RA, IgG responses developed slower with lower peak titres compared with HC. Potent neutralising activity assessed by a SARS-CoV-2 pseudovirus neutralisation assay after 12 weeks was observed in all 21 HCs, and in 60.3% of 73 patients with RA. A significant correlation between peak anti-S IgG levels 2 weeks after the second vaccine dose and potent neutralising activity against SARS-CoV-2 was observed at weeks 12 and 24. The analysis of IgG, IgA and IgM isotype responses to different viral proteins demonstrated a delay in IgG but not in IgA and IgM responses. T cell responses were comparable in HC and patients with RA but declined earlier in patients with RA. CONCLUSION In patients with RA, vaccine-induced IgG antibody levels were diminished, while IgA and IgM responses persisted, indicating a delayed isotype switch. Anti-S IgG levels 2 weeks after the second vaccine dose correlate with the development of a potent neutralising activity after 12 and 24 weeks and may allow to identify patients who might benefit from additional vaccine doses or prophylactic regimen

A murine model of meningeal inflammation and subpial demyelination identifies an anti-MOG independent mechanism of cortical injury that is inhibited by Siponimod therapy

Subpial demyelination is a specific hallmark of multiple sclerosis (MS) and a correlate of disease progression and cognitive decline. Although the mechanism(s) that mediate pathogenesis in this compartment remain unclear, it has been speculated that inflammation in the overlying meninges may be associated with sub-pial injury. We have previously shown that proteolipid-primed Th17 cells adoptively transferred into SJL/J recipient mice induce Experimental Autoimmune Encephalomyelitis (A/T SJL/J EAE) accompanied by extensive stromal cell remodelling and accumulation of lymphocytes in the brain meninges. Here we show that meningeal inflammation in this model overlays areas of subpial cortical demyelination associated with microglial/macrophage activation, disruption of the glial limitans and evidence of an oxidative stress response. These pathological features were observed even in the absence of measurable anti-MOG IgM or IgG antibodies. We took advantage of this model to test potential mechanisms of action of BAF312 (siponimod), a selective sphingosine 1-phosphate (S1P) receptor1,5 modulator. BAF312 treatment significantly ameliorated clinical manifestations of EAE concomitant with diminished meningeal inflammation and subpial pathology and as well as a selective reduction in Th17 cell accumulation in the central nervous system (CNS). We conclude that Th17 cells rather than anti-MOG antibodies are critically required for meningeal inflammation and cortical pathology in A/T SJL/J EAE. Moreover BAF312, a promising MS therapeutic, ameliorates the clinical and pathological features of this model perhaps through its affect on CNS-resident Th17 cells

Postvaccination anti-S IgG levels predict anti-SARS-CoV-2 neutralising activity over 24 weeks in patients with RA

Objectives: To correlate immune responses following a two-dose regimen of mRNA anti-SARS-CoV-2 vaccines in patients with rheumatoid arthritis (RA) to the development of a potent neutralising antiviral activity. Methods: The RECOVER study was a prospective, monocentric study including patients with RA and healthy controls (HCs). Assessments were performed before, and 3, 6, 12 and 24 weeks, after the first vaccine dose, respectively, and included IgG, IgA and IgM responses (against receptor binding domain, S1, S2, N), IFN-γ ELISpots as well as neutralisation assays. Results: In patients with RA, IgG responses developed slower with lower peak titres compared with HC. Potent neutralising activity assessed by a SARS-CoV-2 pseudovirus neutralisation assay after 12 weeks was observed in all 21 HCs, and in 60.3% of 73 patients with RA. A significant correlation between peak anti-S IgG levels 2 weeks after the second vaccine dose and potent neutralising activity against SARS-CoV-2 was observed at weeks 12 and 24. The analysis of IgG, IgA and IgM isotype responses to different viral proteins demonstrated a delay in IgG but not in IgA and IgM responses. T cell responses were comparable in HC and patients with RA but declined earlier in patients with RA. Conclusion: In patients with RA, vaccine-induced IgG antibody levels were diminished, while IgA and IgM responses persisted, indicating a delayed isotype switch. Anti-S IgG levels 2 weeks after the second vaccine dose correlate with the development of a potent neutralising activity after 12 and 24 weeks and may allow to identify patients who might benefit from additional vaccine doses or prophylactic regimen.</p