Every Third Baby with Lymphoma Under 3 Years of Age Has Inborn Error of Immunity
Year: 2025
Type: article
Study design: Observational Study
Abstract: Background and Aims In children under 3 years of age, lymphoma is extremely rare and may be a manifestation of inborn errors of immunity (IEIs). The aim of this study was to determine TREC/KREC copy numbers and search for Slavic founder mutations (RAG1 p.Lys86ValfsTer33, IL7R p.Ser44Arg, NBN1 p.Lys219AsnfsTer16, ATM p.Glu1978Ter, UNC13D p.Arg782SerfsTer12) in patients with lymphoma up to 3 years of age from the Belarusian Cancer Registry (No.: 0170100025) over a 26-year period. Methods From 1998 to 2024, 39 patients younger than 3 years (29 males and 10 females) were diagnosed with lymphoma. The median age was 2.1 years (from 50 days to 2.8 years). 4 patients had Hodgkin's lymphoma (HL), 5—diffuse large B cell lymphoma (DLBCL), 13—lymphoblastic lymphoma (LL), 10—Burkitt lymphoma (BL), 2—peripheral T cell lymphoma (PTCL), 4—anaplastic large cell lymphoma (ALCL), 1—non-Hodgkin's lymphoma (NHL) of unspecified type. DNA was isolated from archival samples from 36 patients: bone marrow smears (n = 12), frozen bone marrow cells (n = 11), and peripheral blood cells (n = 13). Results Lymphoma in children aged 0-3 years accounted 3% (39/1237) of all pediatric lymphoma cases up to 18 years of age, including 7% (35/481) of NHL and 0.5% (4/756) of HL patients. 15/39 (38%) patients died and 3 were lost to follow-up. TREC/KREC copy numbers was reduced in 12/36 (33%) patients, 7 of whom were dead. Low TRECs/KRECs were present in all patients with DLBCL, 2 with ALCL, 2 with LL, and single cases with HL, BL, and PTCL. Homozygosity for the underlying Slavic variant of RAG1 [p.Lys86ValfsTer33] was found in a patient with DLBCL at the age of 14 months. One 12-month-old patient with PTCL was homozygous for the founder Slavic UNC13D variant [p.Arg782SerfsTer12]. Conclusions Low TREC/KREC was detected in one-third of children aged 0-3 years with lymphoma and may be used as a step 1 method to suspect the IEIs.
Source: Journal of Human Immunity
Authors: Tatiana Volodashchik, Ekaterina Polyakova, Inga Sakovich, Aleksandra Kupchinskaya, Alexandra Romantsova, Mikhail Belevtsev, Alina Sojka, Irma Yemialyanava, Marina Horbach, Dmitry Kochubinski, Svetlana Charniayskaja, Taisia Mikhaleuskaya, Luigi Notarangelo, Jolan Walter, Olga Aleinikova, Svetlana Sharapova
Institutions: Belarusian Research Center For Pediatric Oncology and Hematology, Vestische Caritas-Kliniken, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Johns Hopkins University, University of South Florida, Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W4409786490