| Title: |
Diagnostic evaluation of paediatric autoimmune lymphoproliferative immunodeficiencies (ALPID): a prospective cohort study |
| Authors: |
Hägele, P.; Staus, P.; Scheible, R.; Uhlmann, A.; Heeg, M.; Klemann, C.; Maccari, M.E.; Ritterbusch, H.; Armstrong, M.; Cutcutache, I.; Elliott, K.S.; von Bernuth, H.; Leahy, T.R.; Leyh, J.; Holzinger, D.; Lehmberg, K.; Svec, P.; Masjosthusmann, K.; Hambleton, S.; Jakob, M.; Sparber-Sauer, M.; Kager, L.; Puzik, A.; Wolkewitz, M.; Lorenz, M.R.; Schwarz, K.; Speckmann, C.; Rensing-Ehl, A.; Ehl, S.; group, A.S.; Abinun, M.; Abrahamsen, T.; Albert, M.; Almalky, M.; Altaf, S.; Babayeva, R.; Bakhtiar, S.; Baris, S.; Baumann, U.; Becker, M.; Berger, T.; Biebl, A.; Bielack, S.; Biskup, S.; Bismarck, P.; Bode, S.; Borchers, R.; Boztug, C.F.; Brockmann, K.; Bruwier, A.; Buchholz, B.; Cant, A.; Castro, C.N.; Classen, C.; Claviez, A.; Crazzolara, R.; Cuntz, F.; Dąbrowska-Leonik, N.; Derichs, U.; Dückers, G.; Eberl, W.; Ebetsberger-Dachs, G.; Erlacher, M.; Fabre, A.; Faletti, L.; Farmand, S.; Figueiredo, A.; Fischer, M.; Flaadt, T.; Full, H.; Gambineri, E.; Girschick, H.; Goldacker, S.; Grimbacher, B.; Groß, M.; Gruhn, A.J.; Gungoren, E.; Haberfellner, F.; Hague, R.; Hauch, H.; Hauck, F.; Heine, S.; Huisman, E.; Jakovljevic, G.; James, B.; Janda, A.; Janda, M.; Jones, N.; Kaiser-Labusch, P.; Kentouche, K.; Knight, J.; Knirsch, S.; Kontny, U.; Körholz, J.; Krenn, E.Y.; Kuehnle, I.; Kühne, T.; Lee-Dimroth, J.-Y.; Lehmann, H.; Leipold, M.H.; Meinhardt, A.; Mönkemöller, K.; Morbach, H.; Mücke, U.; Nathrath, M.; Naumann-Bartsch, N.; Neth, O.; Niemeyer, C.; Olbrich, P.; Ostró, R.; Owens, S.; Pac, M.; Schmid, R.P.; Page, M.G.; Pekrun, A.; Prader, S.; Proietti, M.; Rajacic, N.; Rothoeft, T.; Ryan, F.H.; Salou, S.; Salzer, E.; Savic, S.; Schilling, A.E.; Schmid, J.; Schönberger, S.; Schuetz, C.; Schuez-Havupalo, T.G.; Schulte, B.; Schulz, A.; Schuster, V.; Seidel, M.; Siepermann, K.; Smisek, P.; Soomann, M.; Stiefel, M.; Storck, S.; Strahm, B.; Streiter, E.J.; Teltschik, C.M.; Thalhammer, J.; Tippelt, S.; Toskov, V.; Trück, J.; Vieth, S.; Wegehaupt, O.; Wiesel, T. |
| Publisher Information: |
Elsevier |
| Publication Year: |
2024 |
| Collection: |
White Rose Research Online (Universities of Leeds, Sheffield & York) |
| Description: |
Background Lymphoproliferation and autoimmune cytopenias characterise autoimmune lymphoproliferative syndrome. Other conditions sharing these manifestations have been termed autoimmune lymphoproliferative syndrome-like diseases, although they are frequently more severe. The aim of this study was to define the genetic, clinical, and immunological features of these disorders to improve their diagnostic classification. Methods In this prospective cohort study, patients were referred to the Center for Chronic Immunodeficiency in Freiburg, Germany, between Jan 1, 2008 and March 5, 2022. We enrolled patients younger than 18 years with lymphoproliferation and autoimmune cytopenia, lymphoproliferation and at least one additional sign of an inborn error of immunity (SoIEI), bilineage autoimmune cytopenia, or autoimmune cytopenia and at least one additional SoIEI. Autoimmune lymphoproliferative syndrome biomarkers were determined in all patients. Sanger sequencing followed by in-depth genetic studies were recommended for patients with biomarkers indicative of autoimmune lymphoproliferative syndrome, while IEI panels, exome sequencing, or genome sequencing were recommended for patients without such biomarkers. Genetic analyses were done as decided by the treating physician. The study was registered on the German Clinical Trials Register, DRKS00011383, and is ongoing. Findings We recruited 431 children referred for autoimmune lymphoproliferative syndrome evaluation, of whom 236 (55%) were included on the basis of lymphoproliferation and autoimmune cytopenia, 148 (34%) on the basis of lymphoproliferation and another SoIEI, 33 (8%) on the basis of autoimmune bicytopenia, and 14 (3%) on the basis of autoimmune cytopenia and another SoIEI. Median age at diagnostic evaluation was 9·8 years (IQR 5·5–13·8), and the cohort comprised 279 (65%) boys and 152 (35%) girls. After biomarker and genetic assessments, autoimmune lymphoproliferative syndrome was diagnosed in 71 (16%) patients. Among the remaining 360 patients, 54 (15%) had ... |
| Document Type: |
article in journal/newspaper |
| Language: |
unknown |
| ISSN: |
2451-9960 |
| Relation: |
Hägele, P., Staus, P., Scheible, R. et al. (146 more authors) (2024) Diagnostic evaluation of paediatric autoimmune lymphoproliferative immunodeficiencies (ALPID): a prospective cohort study. The Lancet Haematology, 11 (2). e114-e126. ISSN: 2451-9960 |
| Availability: |
https://eprints.whiterose.ac.uk/id/eprint/217949/ |
| Accession Number: |
edsbas.1020B764 |
| Database: |
BASE |