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. 2023 Jan 3;9(1):00025-2022.
doi: 10.1183/23120541.00025-2022. eCollection 2023 Jan.

Trimer IgG and neutralising antibody response to COVID-19 mRNA vaccination in individuals with sarcoidosis

Christen L Vagts  1 , Yi-Shin Chang  1   2 , Christian Ascoli  1 , Jessica M Lee  1   3 , Kai Huang  1   2 , Yue Huang  1 , Ruth A Cherian  1 , Nandini Sarup  1 , Samantha R Warpecha  1 , Russell Edafetanure-Ibeh  1 , Md-Ruhul Amin  1 , Tasmin Sultana  1 , Mahmood Ghassemi  1 , Nadera J Sweiss  1 , Richard Novak  1 , David L Perkins  1   2   4   5 , Patricia W Finn  1   2   3   5
Affiliations

Trimer IgG and neutralising antibody response to COVID-19 mRNA vaccination in individuals with sarcoidosis

Christen L Vagts et al. ERJ Open Res. .

Abstract

Background: Individuals with sarcoidosis are at higher risk for infection owing to underlying disease pathogenesis and need for immunosuppressive treatment. Current knowledge as to how subjects with sarcoidosis respond to different forms of vaccination is limited. We examined quantitative and functional antibody response to COVID-19 vaccination in infection-naive subjects with and without sarcoidosis.

Methods: Our prospective cohort study recruited 14 subjects with biopsy-proven sarcoidosis and 27 age-sex matched controls who underwent a two-shot series of the BNT162b2 mRNA vaccine at the University of Illinois at Chicago. Baseline, 4-week and 6-month trimer spike protein IgG and neutralising antibody (nAb) titres were assessed. Correlation and multivariate regression analysis was conducted.

Results: Sarcoidosis subjects had a significant increase in short-term antibody production to a level comparable to controls; however, IgG titres significantly declined back to baseline levels by 6 months. Corresponding neutralising assays revealed robust nAb titres in sarcoidosis subjects that persisted at 6 months. A significant and strong correlation between IgG and nAb titres across all time points was observed in the control group. However within the sarcoidosis group, a significant but weak correlation between antibody levels was found. Overall, IgG levels were poor predictors of nAb titres at short- or long-term time points.

Conclusions: Sarcoidosis subjects exhibit nAb induced by the BNT162b2 mRNA SARS-CoV-2 vaccine at levels comparable to controls that persists at 6 months indicating conferred immunity. Trimer IgG levels are poor predictors of nAb in subjects with sarcoidosis. Studies of further antibody immunoglobulins and subtypes warrant investigation.

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Conflict of interest statement

Conflict of interest: Richard M. Novak reports the following relationships outside the submitted work: grants or contracts received from Janssen; consulting fees received from Gilead and Viiv. The remaining authors have nothing to disclose.

Figures

FIGURE 1
FIGURE 1
Trimer IgG titres for control and sarcoidosis groups are shown: a) log transformed titres for comparison between time points for each group; and b) log transformed titres for comparison between groups at each time point. NS: p>0.05; *: p≤0.05; ***: p≤0.001. NS: nonsignificant.
FIGURE 2
FIGURE 2
Neutralising titres (50% inhibitory dilution (ID50)) for control and sarcoidosis groups are shown: a) log transformed titres for comparison between time points for each group and b) log transformed titres for comparison between groups at each time point. NS: p>0.05; ***: p≤0.001.
FIGURE 3
FIGURE 3
a) log transformed trimer spike protein IgG titres are shown. Sarcoidosis subjects not on treatment had significantly higher V1D0 titres than controls and comparable titres at V2D7. M6 IgG titres were significantly lower in the sarcoidosis group than controls. b) log transformed neutralising titres (50% inhibitory dilution (ID50)). Values were comparable across all groups at each time point. NS: p>0.05; *: p≤0.05; ***: p≤0.001.
FIGURE 4
FIGURE 4
Univariate linear regression analysis illustrating the relationship between log transformed trimer IgG titres and log transformed 50% inhibitory dilution (ID50) across all time points. a) Control group showing a significant and strong correlation; b) sarcoidosis group showing a significant yet weak correlation.
FIGURE 5
FIGURE 5
Multivariate regression analysis to assess independent predictors of 50% inhibitory dilution (ID50) by group (top row: controls; bottom row: sarcoidosis) and outcome time points (left column: V2D7; right column: M6). Axes are log transformed. a) V2D7 ID50 for control group. Model: Log10 V2D7 ID50 ∼ Log10 V2D7 Trimer IgG * Log10 V1D0 Trimer IgG + Race + BMI. b) M6 ID50 for the control group. Model: Log10 V2D7 ID50 ∼ Log10 V2D7 Trimer IgG * Log10 V1D0 Trimer IgG + Log10 V2D7 Trimer IgG * Log10 M6 V2D7 IgG + Race + BMI. c) V2D7 ID50 for the sarcoidosis group. Model: Log10 V2D7 ID50 ∼ Log10 V2D7 Trimer IgG * Log10 V1D0 Trimer IgG + Race + BMI + Treatment Group. d) M6 ID50 for the sarcoidosis group. Log10 V2D7 ID50 ∼ Log10 V2D7 Trimer IgG * Log10 V1D0 Trimer IgG + Log10 V2D7 Trimer IgG * Log10 M6 V2D7 IgG + Race + BMI + Treatment Group. The overall regression was not statistically significant for either group at both time points.
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