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<p>MS is the result of an immune-mediated disorder triggered by environmental factors in subjects genetically predisposed. Pediatric MS (pedMS) offers a unique window to study environmental triggers, as&#xa0;patients are close to the actual onset of the disease and have been exposed to fewer confounding&#xa0;factors. PedMS is strongly associated to HLA-DRB1*15:01 and to non–MHC (Major Histocompatibility Complex) variants, with a higher burden compared to adults. HLA-A*02 allele seems to reduce MS risk. The role of rare variants is still under investigation. Several environmental causative factors have been identified: obesity, passive smoke, sun exposure, vitamin D, and others but the&#xa0;strongest candidate is the Epstein-Barr virus, considered a prerequisite for MS development. In this paper we provide a summary of the results obtained so far in pediatric age. Some years ago, the Italian PEDIGREE study (<Emphasis Type="Underline">PED</Emphasis>iatric&#xa0;<Emphasis Type="Underline">I</Emphasis>talian&#xa0;<Emphasis Type="Underline">G</Emphasis>enetic and envi<Emphasis Type="Underline">R</Emphasis>onmental&#xa0;<Emphasis Type="Underline">E</Emphasis>xposur<Emphasis Type="Underline">E</Emphasis>) has been created to help clarify the role of genetic and environmental factors in pedMS, through a study of the genetic, epigenetic, metagenomic, transcriptomic, along with assessment of environmental factors (viral exposure, second-hand smoke and sun exposure, breastfeeding history, and other factors. A network of 29 Italian MS centers has been established, 154 pedMS patients (mean age 13.5&#xa0;years) and matched controls have been recruited. For the genetic study, a cohort of 364 adult MS patients with onset &lt; 18&#xa0;years was included. The study is ongoing, the results of exposure to environmental risk factors and of genetic background will be available in the next future.</p>

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A narrative review of genetic and environmental factors and risk for multiple sclerosis. The design of the Italian multicentric PEDIGREE study

  • 期刊论文

  • 发表日期：

    2025年8月15日

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  • Angelo Ghezzi,
  • Sandra D’Alfonso,
  • Maura Pugliatti,
  • Silvy Pilotto,
  • Martina Tosi,
  • Andrea Corona,
  • Alen Zollo,
  • Nicola Pomella,
  • Maria Pia Amato,
  • Eleonora Cocco,
  • Maria Trojano,
  • Roberto Bergamaschi,
  • Filippo Martinelli-Boneschi,
  • Martina Tosi,
  • Nicola Pomella,
  • Maurizio Viri,
  • Amanda Papa,
  • Fabio Brustia,
  • Domizia Vecchio,
  • Eleonora Cocco,
  • Gabriella Spinicci,
  • Maria Fronza,
  • Maria Rita Murru,
  • Valentina Fadda,
  • Filippo Martinelli Boneschi,
  • Alen Zollo,
  • Andrea Corona,
  • Alessandra Mingione,
  • Maria Trojano,
  • Pietro Iaffaldano,
  • Damiano Paolicelli,
  • Alessia Manni,
  • Marta Simone,
  • Maria Pia Amato,
  • Emilio Portaccio,
  • Camilla Masciulli,
  • Giuseppe Santangelo,
  • Antonio Marino,
  • Andrea Santangelo,
  • Sarah Rasia,
  • Ruggero Capra,
  • Lucia Moiola,
  • Chiara Zanetta,
  • Federica Esposito,
  • Vincenzo Brescia Morra,
  • Roberta Lanzillo,
  • Simona Malucchi,
  • Martina Borghi,
  • Paola Valentino,
  • Gioacchino Tedeschi,
  • Antonio Gallo,
  • Alvino Bisecco,
  • Roberto Bergamaschi,
  • Stefano Parravicini,
  • Pietro Annovazzi,
  • Mattia Pozzato,
  • Patrizia Carta,
  • Agnese Suppiej,
  • Valentina Liliana Adriana Torri Clerici,
  • Alessandra Tozzo,
  • Alessandra Protti,
  • Lorenzo Saraceno,
  • Carlo Pozzilli,
  • Viola Baione,
  • Giorgia DAmbrosi,
  • Stefano Sotgiu,
  • Alessandra Carta,
  • Marta Zaffira Conti,
  • Marta Radaelli,
  • Stefania Maria Bova,
  • Arianna Gadda,
  • Valentina Tomassini,
  • Giovanna De Luca,
  • Luigi Maria Edoardo Grimaldi,
  • Oscar Oddo,
  • Francesco Patti,
  • Luca Maria,
  • Chisari Clara,
  • Toscano Simona,
  • Finocchiaro Chiara,
  • Giacomo Lus,
  • Marcella Coletta,
  • Carlotta Canavese,
  • Angela Berardinelli,
  • Sara Fusco,
  • Girolama Alessandra Marfia,
  • Carolina Gabri Nicoletti,
  • Doriana Landi,
  • Salvatore Cottone,
  • Maura Pugliatti,
  • Silvy Pilotto,
  • Caterina Ferri,
  • Michele Laudisi,
  • Eleonora Baldi

摘要

MS is the result of an immune-mediated disorder triggered by environmental factors in subjects genetically predisposed. Pediatric MS (pedMS) offers a unique window to study environmental triggers, as patients are close to the actual onset of the disease and have been exposed to fewer confounding factors. PedMS is strongly associated to HLA-DRB1*15:01 and to non–MHC (Major Histocompatibility Complex) variants, with a higher burden compared to adults. HLA-A*02 allele seems to reduce MS risk. The role of rare variants is still under investigation. Several environmental causative factors have been identified: obesity, passive smoke, sun exposure, vitamin D, and others but the strongest candidate is the Epstein-Barr virus, considered a prerequisite for MS development. In this paper we provide a summary of the results obtained so far in pediatric age. Some years ago, the Italian PEDIGREE study (PEDiatric Italian Genetic and enviRonmental ExposurE) has been created to help clarify the role of genetic and environmental factors in pedMS, through a study of the genetic, epigenetic, metagenomic, transcriptomic, along with assessment of environmental factors (viral exposure, second-hand smoke and sun exposure, breastfeeding history, and other factors. A network of 29 Italian MS centers has been established, 154 pedMS patients (mean age 13.5 years) and matched controls have been recruited. For the genetic study, a cohort of 364 adult MS patients with onset < 18 years was included. The study is ongoing, the results of exposure to environmental risk factors and of genetic background will be available in the next future.