Investigating Biomarkers for Inborn Errors of Immunity in a Prospective Study of Patients With Autoimmune Cytopenia.
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Gaál Zsuzsanna, Meehan Cristina, Yilmaz Melis, Ujhazi Boglarka, Suhet Paola, Miller Rahim, Dasso Joseph, Nomula Kranthi, Franson Brady, Toth Marta, Potts Evan, Gokbak Merve Nida, Gordon Sumai, Ellison Maryssa, Cruz Rachel, Asante-Korang Alfred, Cassani Frank Ayestaran, Betensky Marisol, Butte Manish, Cooper Meagan Anne, Cockrell Erin, Galligan Andrew, Glaum Mark, Grimbacher Bodo, Fliegauf Manfred, Meyer Anna, Milojevic Diana, Minor Mark, Mendez Elvin M, Metts Jonathan, Nieves Daime, Ong Mei-Sing, Oshrine Benjamin R, Patel Priya, Prpich John, Purser Jane, Ramirez Alina, Rosenberg David, Schlefman Amanda, Shaker Ahmad, Shah Shalin, Shah Bijal, Santiago Laisa, Obzut Dana, Sriaroon Panida, Thatayatikom Akaluck, Weis Emily, Mayer Jennifer, Farmer Jocelyn R, Csomos Krisztian, Eslin Don, Ayala Irmel, Westermann-Clark Emma, Walter Jolan E
Аннотация
METHODS: Clinical phenotype and genetic causes of IEI were assessed using targeted panel-based sequencing. Unique lymphocyte subsets, including activated naïve and transitional B cells, CD19hiCD21lo B cells, follicular helper T (TFH) cells, regulatory T (Treg) cells, and TCRαβ+CD4-CD8- double-negative T cells (DNTαβ), were assessed by flow cytometry. Serum levels of lipopolysaccharide (LPS), B-cell activating factor (BAFF), and soluble IL-2 receptor (sIL2R) were quantified by ELISA.
RESULTS: Among 104 AIC patients, 53 (51%) showed evidence of IEI, including 27 (26%) with monogenic disorders-most commonly partial DiGeorge syndrome (pDGS), followed by variants in NFKB1, CTLA4, and FAS. The prevalence of IEI was highest in autoimmune hemolytic anemia (AIHA) (62.5%) and Evans syndrome (61.5%). Low levels of IgG, IgA, and IgM, as well as reduced percentages of naïve CD4+ and CD8+ T cells, were significantly associated with increased odds of IEI. In AIC-IEI patients, transitional B cells, CD19hiCD21lo B cells, and TFH cells were expanded, accompanied by elevated serum levels of BAFF and sIL2R.
CONCLUSIONS: Quantitative immunoglobulin levels and naïve T cells remain valuable indicators of IEI in AIC. Our findings highlight the diagnostic value of emerging cellular and serum biomarkers in identifying IEI, including dysregulation of early B-cell subsets (transitional B cells and CD19hiCD21lo B cells), expansion of TFH cells, and elevated levels of BAFF and sIL2R.