Immunophenotype by spectral cytometry reveals a lymphopenia profile associated with dysregulation, with an increase in effector memory lymphocytes in a patient with an ITPR3 gene mutation

Abstract

Background: Variants in genes involved in intracellular calcium transport have been associated with syndromic immunodeficiencies presenting with a SCID-like phenotype.

Case report: A seven-year-old girl from Cartagena, Colombia, born to non-consanguineous parents. At two months of age, she presented with hematochezia and was diagnosed with food proctocolitis, which did not improve with the exclusion of milk, wheat, and egg, leading to malnutrition. At eight months, a colon biopsy showed chronic lymphoid hyperplasia. She had anemia, eosinophilia, but normal total and specific IgE levels for foods. At four years, the Immunology Service found her asymptomatic, nutritionally recovered, and without allergic sensitization; however, eosinophilia and elevated calprotectin persisted, suggesting early-onset inflammatory bowel disease. Immunoglobulin levels were normal, but lymphocyte populations showed CD3, CD4, and CD8 lymphopenia. At six years, she developed atopic dermatitis, continued with elevated calprotectin, and remained lymphopenic.

Immunophenotyping by spectral cytometry using the Cytek®cFluor®Immunoprofiling-Kit14 revealed lymphopenia and CD4/CD8 inversion. CD4+ and CD8+ naive T cells were reduced, whereas effector memory T-CD8+CD45RA-CCR7- and T-CD8+CD45RA+CCR7– populations were expanded. Effector and central memory T-CD4+ lymphocytes were also increased (Figure 1). Whole-exome sequencing identified a heterozygous variant in the ITPR3 gene (paternal carrier), c.7571G>A, p.(Arg2524His), classified by predictors as potentially deleterious.

Conclusions: The clinical presentation and immunophenotype of this candidate variant differ from other conditions related to intracellular calcium transport. Functional studies are required to validate its causality. A patient with a potentially deleterious variant presents with CD3 lymphopenia and persistent lymphocyte activation.