{Reference Type}: Journal Article
{Title}: Newborn Screening for Severe T and B Cell Lymphopenia Using TREC/KREC Detection: A Large-Scale Pilot Study of 202,908 Newborns.
{Author}: Marakhonov AV;Efimova IY;Mukhina AA;Zinchenko RA;Balinova NV;Rodina Y;Pershin D;Ryzhkova OP;Orlova AA;Zabnenkova VV;Cherevatova TB;Beskorovainaya TS;Shchagina OA;Polyakov AV;Markova ZG;Minzhenkova ME;Shilova NV;Larin SS;Khadzhieva MB;Dudina ES;Kalinina EV;Mudaeva DA;Saydaeva DH;Matulevich SA;Belyashova EY;Yakubovskiy GI;Tebieva IS;Gabisova YV;Irinina NA;Nurgalieva LR;Saifullina EV;Belyaeva TI;Romanova OS;Voronin SV;Shcherbina A;Kutsev SI;
{Journal}: J Clin Immunol
{Volume}: 44
{Issue}: 4
{Year}: 2024 Apr 5
{Factor}: 8.542
{DOI}: 10.1007/s10875-024-01691-z
{Abstract}: Newborn screening (NBS) for severe inborn errors of immunity (IEI), affecting T lymphocytes, and implementing measurements of T cell receptor excision circles (TREC) has been shown to be effective in early diagnosis and improved prognosis of patients with these genetic disorders. Few studies conducted on smaller groups of newborns report results of NBS that also include measurement of kappa-deleting recombination excision circles (KREC) for IEI affecting B lymphocytes. A pilot NBS study utilizing TREC/KREC detection was conducted on 202,908 infants born in 8 regions of Russia over a 14-month period. One hundred thirty-four newborns (0.66‰) were NBS positive after the first test and subsequent retest, 41% of whom were born preterm. After lymphocyte subsets were assessed via flow cytometry, samples of 18 infants (0.09‰) were sent for whole exome sequencing. Confirmed genetic defects were consistent with autosomal recessive agammaglobulinemia in 1/18, severe combined immunodeficiency - in 7/18, 22q11.2DS syndrome - in 4/18, combined immunodeficiency - in 1/18 and trisomy 21 syndrome - in 1/18. Two patients in whom no genetic defect was found met criteria of (severe) combined immunodeficiency with syndromic features. Three patients appeared to have transient lymphopenia. Our findings demonstrate the value of implementing combined TREC/KREC NBS screening and inform the development of policies and guidelines for its integration into routine newborn screening programs.