The following is a summary of “Diagnosis of severe combined immunodeficiency: Implementation of the PIDTC 2022 Definitions,” published in the FEBRUARY 2023 issue of Allergy & Immunology by Dvorak, et al.
As part of the prospective and retrospective investigations on severe combined immunodeficiency (SCID) conducted by the Primary Immune Deficiency Therapy Consortium (PIDTC), Shearer et al. 2014 developed precise criteria for the diagnosis and classification of SCID. However, the PIDTC 2014 Criteria must be revised due to the introduction of neonatal SCID screening and the expansion of available genetic sequencing.
By examining 379 patients who were suggested for prospective participation in Protocol 6901, researchers established and tested updated PIDTC 2022 SCID Definitions with a focus on the capability to identify patients with different SCID subtypes.
According to PIDTC 2022 Definitions, 11 of 26 patients ineligible for the 2014 Criteria were found to have SCID, compared to 18 of 353 eligible patients who were not SCID-positive. Typical SCID under the 2022 Definitions was characterized by extremely low autologous T cell counts (<0.05 109/L). In 93% of patients, pathogenic variant(s) in SCID-associated genes were found, with 7 genes (IL2RG, RAG1, ADA, IL7R, DCLRE1C, JAK3, & RAG2) being responsible for 89% of typical SCID. There were 13 additional uncommon genotypes, but three genotypes (RAG1, ADA, & RMRP) accounted for 57% of leaky/atypical SCID cases. Patients with leaky/atypical SCID had a 20% higher chance of being identified at or after age 1 year than those with typical SCID without maternal T cells: 20% versus 1% (P<.001). Although additional testing was crucial, cases of typical SCID without maternal lymphocytes were distinguished from leaky/atypical SCID in 97% of cases (P< .001) by an initial CD3 T-cell count of < 0.05 109/L.
The PIDTC 2022 Definitions provided a more detailed description of SCID and its subtypes than previous definitions, improving the analysis of SCID traits and outcomes.
Reference: jacionline.org/article/S0091-6749(22)01478-6/fulltext