Frontiers in Immunology (Jul 2024)

Flow cytometry-based diagnostic approach for inborn errors of immunity: experience from Algeria

  • Azzeddine Tahiat,
  • Reda Belbouab,
  • Abdelghani Yagoubi,
  • Saliha Hakem,
  • Faiza Fernini,
  • Malika Keddari,
  • Hayet Belhadj,
  • Souad Touri,
  • Samira Aggoune,
  • Jennifer Stoddard,
  • Julie Niemela,
  • Farida Zerifi,
  • Souhila Melzi,
  • Rawda Aboura,
  • Amina Saad-Djaballah,
  • Yacine Ferhani,
  • Abdalbasset Ketfi,
  • Hassen Messaoudi,
  • Tahar Bencharif Madani,
  • Zouleikha Benhacine,
  • Abdelhak Dehimi,
  • Kamelia Okka,
  • Fairouz Amroune,
  • Meriem Fellahi,
  • Chafa Bendahmane,
  • Radia Khoulani,
  • Asma Oukil,
  • Asma Soufane,
  • Imene Bourelaf,
  • Chahynez Boubidi,
  • Nadia Boukhenfouf,
  • Mohamed Amine Ifri,
  • Noureddine Khelafi,
  • Houda Boudiaf,
  • Tahar Khelifi Touhami,
  • Fethi Meçabih,
  • Malika Boucelma,
  • Amara Zelaci,
  • Ourida Gacem,
  • Mohamed Samir Ladj,
  • Azzedine Mekki,
  • Nadia Bensaadi,
  • Malika Benhalima,
  • Zoulikha Zeroual,
  • Belkacem Bioud,
  • Mustapha Benameur,
  • Rachid Bouhdjila,
  • Zahir Bouzerar,
  • Ouardia Ibsaine,
  • Hachemi Maouche,
  • Leila Kedji,
  • Leila Smati,
  • Rachida Boukari,
  • Claude Lambert,
  • Sergio D. Rosenzweig,
  • Luigi D. Notarangelo,
  • Kamel Djenouhat

DOI
https://doi.org/10.3389/fimmu.2024.1402038
Journal volume & issue
Vol. 15

Abstract

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PurposeIn this study, we retrospectively reviewed the use of flow cytometry (FCM) in the diagnosis of inborn errors of immunity (IEIs) at a single center in Algeria. Sharing insights into our practical experience, we present FCM based diagnostic approaches adapted to different clinical scenarios.MethodsBetween May 2017 and February 2024, pediatric and adult patients presenting with clinical features suggestive of immunodeficiency were subjected to FCM evaluation, including lymphocyte subset analysis, detection of specific surface or intracellular proteins, and functional analysis of immune cells.ResultsOver a nearly seven-year period, our laboratory diagnosed a total of 670 patients (372 (55.5%) males and 298 (44.5%) females), distributed into 70 different IEIs belonging to 9 different categories of the International Union of Immunological Societies classification. FCM was used to diagnose and categorize IEI in 514 patients (76.7%). It provided direct diagnostic insights for IEIs such as severe combined immunodeficiency, Omenn syndrome, MHC class II deficiency, familial hemophagocytic lymphohistiocytosis, and CD55 deficiency. For certain IEIs, including hyper-IgE syndrome, STAT1-gain of function, autoimmune lymphoproliferative syndrome, and activated PI3K delta syndrome, FCM offered suggestive evidence, necessitating subsequent genetic testing for confirmation. Protein expression and functional assays played a crucial role in establishing definitive diagnoses for various disorders. To setup such diagnostic assays at high and reproducible quality, high level of expertise is required; in house reference values need to be determined and the parallel testing of healthy controls is highly recommended.ConclusionFlow cytometry has emerged as a highly valuable and cost-effective tool for diagnosing and studying most IEIs, particularly in low-income countries where access to genetic testing can be limited. FCM analysis could provide direct diagnostic insights for most common IEIs, offer clues to the underlying genetic defects, and/or aid in narrowing the list of putative genes to be analyzed.

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