Lindahl H, Shaw-Saliba K, Larman HB, Smith CIE, Bergman P. *European Journal of Immunology* · March 2026 · DOI: [10.1002/eji.70162](https://doi.org/10.1002/eji.70162) How to cite ### AMA Lindahl H, Shaw-Saliba K, Larman HB, Smith CIE, Bergman P. Viral immunity in immunoglobulin products, global immunity debt and autoimmunity. *Eur J Immunol*. 2026;56(3):e70162. doi:10.1002/eji.70162 ### APA ``` Lindahl, H., Shaw-Saliba, K., Larman, H. B., Smith, C. I. E., & Bergman, P. (2026). Viral immunity in immunoglobulin products, global immunity debt and autoimmunity. *European Journal of Immunology*, 56(3), e70162. https://doi.org/10.1002/eji.70162 ``` ### BibTeX ``` @article{lindahl2026viral, title = {Viral immunity in immunoglobulin products, global immunity debt and autoimmunity}, author = {Lindahl, Hannes and Shaw-Saliba, Katy and Larman, H. Benjamin and Smith, C. I. Edvard and Bergman, Peter}, journal = {European Journal of Immunology}, volume = {56}, number = {3}, pages = {e70162}, year = {2026}, doi = {10.1002/eji.70162}, pmid = {41817353} } ``` Lindahl and colleagues profiled **85 immunoglobulin (Ig) replacement therapy batches** — each pooled from more than 1,000 plasma donors and produced between May 2017 and June 2023 — against more than 283,000 viral peptides drawn from 527 virus species, and against a parallel human autoantigen panel. The six-year longitudinal design captured the antibody-supply signature of the COVID-19 pandemic in real time: SARS-CoV-2 antibodies emerging from July 2021 onward, lockdown-era declines in influenza, HSV-1, and enterovirus C, and a parallel rise in autoantibodies against TRIM21/Ro52 alongside SARS-CoV-2 reactivity — reframing pooled Ig products as a continuous longitudinal census of donor-population immunity, not a fixed antibody mix. [ Read publication at European Journal of Immunology ](https://doi.org/10.1002/eji.70162) In this publication: - **Cohort scale:** 85 immunoglobulin batches profiled across six years (May 2017–June 2023), each pooled from >1,000 plasma donors and screened against >283,000 viral peptides spanning 527 virus species. - **Pandemic-era immunity debt:** antibodies against influenza, HSV-1, and enterovirus C declined during 2020–2021, while RSV and Epstein-Barr virus antibodies rose — the supply-side fingerprint of lockdown-driven exposure suppression. - **SARS-CoV-2 emergence:** SARS-CoV-2 antibodies were absent before mid-2021 and appeared in batches manufactured from July 2021 onward, tracking donor vaccination and natural infection. - **Autoimmunity marker:** autoantibodies against 55 human proteins were detected across the product set; TRIM21/Ro52 reactivity rose in parallel with SARS-CoV-2 antibodies, with manufacturer-specific autoantibody effects emerging from PCA. Patients with low IgG levels — whether from primary immunodeficiency, secondary immunodeficiency, or treatment-induced hypogammaglobulinemia — depend on regular intravenous or subcutaneous infusions of pooled plasma-derived immunoglobulin. Because each Ig batch is pooled from thousands of healthy donors worldwide, those infusions also act as a longitudinal census of the antibody repertoire circulating in the donor population at the time of collection. This study used that property to read the immunological signature of the COVID-19 pandemic directly out of the Ig supply. The investigators examined 85 Ig batches produced between May 2017 and June 2023, spanning the period before, during, and after the pandemic. Using a high-throughput antibody-reactome assay that profiles binding against more than 283,000 viral peptides drawn from 527 virus species, they traced how the antibody composition of those Ig products shifted over six years, and screened the same batches for reactivity against a panel of human autoantigens. Antibodies against more than 200 virus species were detectable across the cohort, and 27 species — predominantly respiratory and herpesviruses — were present in more than half the batches, reflecting the high underlying seroprevalence of those infections in donor populations. SARS-CoV-2 antibodies were absent before mid-2021 and appeared in products manufactured from July 2021 onward. The pandemic period also produced measurable shifts in non-SARS antibodies: influenza, HSV-1, and enterovirus C antibodies fell — the Ig-supply reflection of the reduced viral circulation that followed nonpharmaceutical interventions — while RSV and Epstein-Barr virus antibodies rose. This is the supply-side fingerprint of *global immunity debt*: a population-level shift in baseline immunity that propagates from circulating antibodies in donors into the Ig products dispensed to patients. In parallel, autoantibodies against 55 human proteins were detected across the batches, with TRIM21/Ro52 reactivity rising alongside SARS-CoV-2 antibodies and manufacturer-specific autoantibody effects emerging from principal component analysis — reframing pooled Ig as a measurable substrate for autoreactivity research and a deployable readout for plasma-fractionator quality monitoring. 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