Faculté de médecine Faculté de médecine

Alessandro Borghesi

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Dr Alessandro Borghesi

Dr Alessandro Borghesi’s research, currently conducted across Italy and Switzerland, focuses on identifying monogenic conditions — or their autoimmune phenocopies — that may lead to immune deficiencies and contribute to severe infectious or post-infectious outcomes, particularly during viral and bacterial infections. His work encompasses infections occurring throughout life, ranging from those affecting the maternal–fetal unit, newborns, and infants during the early postnatal period to infections affecting older children, adults, and elderly individuals. In this context, he plays an active role in the international consortium COVID-19 Human Genetic Effort.

In 2022, Dr Borghesi discovered that circulating autoantibodies neutralizing type I interferons (IFN-α2, IFN-β, and IFN-ω) underlie approximately 40% of cases of West Nile virus (WNV) encephalitis. He subsequently led an international collaborative effort that confirmed these findings across six independent international cohorts (Gervais et al., Journal of Experimental Medicine, 2023) and seven additional cohorts (Gervais et al., Journal of Human Immunity, 2026). This work resolved a decades-long enigma surrounding the pathogenesis of WNV encephalitis and established WNV encephalitis as one of the best immunologically characterized human infections to date. More broadly, this discovery builds on previous work on severe viral respiratory infections — including severe influenza and COVID-19 — to which he contributed, and expands the field of inborn errors of immunity and autoimmune phenocopies in arthropod-borne infectious diseases.

Selected ongoing projects include:

  • Inborn errors of immunity underlying neonatal bacterial infections (including group B streptococcus, Escherichia coli, Klebsiella spp., and others)
  • Inborn errors of immunity underlying neonatal inflammatory disorders, including necrotizing enterocolitis and fulminant viral hepatitis
  • Inborn errors of immunity and autoimmune phenocopies underlying pediatric and adult respiratory disorders, including bronchiolitis (RSV, hRV, hMPV), critical influenza pneumonia, and COVID-19
  • Inborn errors of immunity and autoimmune phenocopies underlying pediatric and adult encephalitis, including WNV and tick-borne encephalitis (TBE)

EXPERTISE

Dr Alessandro Borghesi uses a forward genetic approach to identify human genetic variants underlying inborn errors of antiviral or antibacterial immunity, as well as inborn errors of immune dysregulation, combined with functional studies to establish causality. In parallel, he applies both targeted and proteome-wide screening approaches for anti-cytokine autoantibodies to identify autoimmune phenocopies of inborn errors of immunity. This work is supported by an international network of clinicians involved in patient recruitment and scientists providing pathway-specific expertise relevant to both endemic/endemo-epidemic and emerging or re-emerging infectious diseases, including hantavirus infections.

Within the GCIR, Dr Borghesi contributes expertise in:

  • Exome and genome sequencing data processing and variant discovery applied to infectious and inflammatory phenotypes
  • Targeted and proteome-wide screening for circulating anti-cytokine autoantibodies

SELECTED PUBLICATIONS

  • Gervais A, Trespidi F, Ferrari A, Rovida F, Marchal A, Croce S, Cassaniti I, Moratti M, Uhrlaub JL, Florian DM, Stiasny K, et al. Autoantibodies neutralizing type I IFNs in 40% of patients with WNV encephalitis in seven new cohorts. J Hum Immun. 2026 Mar 13;2(3):e20250189. doi: 10.1084/jem.20230661 PMID: 41836040.
  • Ferrari A, Cassaniti I, Rovida F, Lilleri D, Croce S, Trespidi F, Ghirardello S, Gervais A, Zhang SY, Casanova JL, Borghesi A, Baldanti F. Human type I interferons protect Vero E6 and ARPE-19 cells against West Nile virus and are neutralized by pathogenic autoantibodies. Sci Rep. 2025 Apr 2;15(1):11271. doi: 10.1038/s41598-025-89312-6. PMID: 40175402.
  • Gervais A, Rovida F, Avanzini MA, Croce S, Marchal A, Lin SC, Ferrari A, Thorball CW, Constant O, Le Voyer T, Philippot Q, et al. Autoantibodies neutralizing type I IFNs underlie West Nile virus encephalitis in ∼40% of patients. J Exp Med. 2023 Sep 4;220(9):e20230661. doi: 10.1084/jem.20230661. PMID: 37347462.
  • Piralla A, Borghesi A, Di Comite A, Giardina F, Ferrari G, Zanette S, Figar TA, Angelini M, Pisoni C, Pitrolo AMG, Paolucci S, et al. Fulminant echovirus 11 hepatitis in male non-identical twins in northern Italy, April 2023. Euro Surveill. 2023 Jun;28(24). doi: 10.2807/1560-7917.ES.2023.28.24.2300289. PMID: 37318763.
  • Borsani O, Bastard P, Rosain J, Gervais A, Sant'Antonio E, Vanni D, Casetti IC, Pietra D, Trotti C, Catricalà S, Ferretti VV, et al. Autoantibodies against type I IFNs in patients with Ph-negative myeloproliferative neoplasms. Blood. 2022 Apr 28;139(17):2716-20. doi: 10.1182/blood.2021014890. PMID: 35100354.

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