TY - JOUR
T1 - Primary Immunodeficiency in Children With Autoimmune Cytopenias
T2 - Retrospective 154-Patient Cohort
AU - Westermann-Clark, Emma
AU - Meehan, Cristina Adelia
AU - Meyer, Anna K.
AU - Dasso, Joseph F.
AU - Amre, Devendra
AU - Ellison, Maryssa
AU - Patel, Bhumika
AU - Betensky, Marisol
AU - Hauk, Charles Isaac
AU - Mayer, Jennifer
AU - Metts, Jonathan
AU - Leiding, Jennifer W.
AU - Sriaroon, Panida
AU - Kumar, Ambuj
AU - Ayala, Irmel
AU - Walter, Jolan E.
N1 - Funding Information:
This research was partly funded by Johns Hopkins All Children’s Hospital (JHACH) Institutional Grant entitled “Feasibility study to assess the role of T and B cells in refractory cytopenias in children” (JW), the Jeffrey Modell Foundation, Jeffrey Modell
Funding Information:
We thank Sharon Crabtree, Senior Data Analytics Specialist for Johns Hopkins All Children’s Hospital Health Informatics, for her efforts and assistance with the database searches of the electronic medical record system and generated reports for our retrospective analysis.
Publisher Copyright:
© Copyright © 2021 Westermann-Clark, Meehan, Meyer, Dasso, Amre, Ellison, Patel, Betensky, Hauk, Mayer, Metts, Leiding, Sriaroon, Kumar, Ayala and Walter.
PY - 2021/4/22
Y1 - 2021/4/22
N2 - Background: Primary immunodeficiency is common among patients with autoimmune cytopenia. Objective: The purpose of this study is to retrospectively identify key clinical features and biomarkers of primary immunodeficiency (PID) in pediatric patients with autoimmune cytopenias (AIC) so as to facilitate early diagnosis and targeted therapy. Methods: Electronic medical records at a pediatric tertiary care center were reviewed. We selected 154 patients with both AIC and PID (n=17), or AIC alone (n=137) for inclusion in two cohorts. Immunoglobulin levels, vaccine titers, lymphocyte subsets (T, B and NK cells), autoantibodies, clinical characteristics, and response to treatment were recorded. Results: Clinical features associated with AIC-PID included splenomegaly, short stature, and recurrent or chronic infections. PID patients were more likely to have autoimmune hemolytic anemia (AIHA) or Evans syndrome than AIC-only patients. The AIC-PID group was also distinguished by low T cells (CD3 and CD8), low immunoglobulins (IgG and IgA), and higher prevalence of autoantibodies to red blood cells, platelets or neutrophils. AIC diagnosis preceded PID diagnosis by 3 years on average, except among those with partial DiGeorge syndrome. AIC-PID patients were more likely to fail first-line treatment. Conclusions: AIC patients, especially those with Evans syndrome or AIHA, should be evaluated for PID. Lymphocyte subsets and immune globulins serve as a rapid screen for underlying PID. Early detection of patients with comorbid PID and AIC may improve treatment outcomes. Prospective studies are needed to confirm the diagnostic clues identified and to guide targeted therapy.
AB - Background: Primary immunodeficiency is common among patients with autoimmune cytopenia. Objective: The purpose of this study is to retrospectively identify key clinical features and biomarkers of primary immunodeficiency (PID) in pediatric patients with autoimmune cytopenias (AIC) so as to facilitate early diagnosis and targeted therapy. Methods: Electronic medical records at a pediatric tertiary care center were reviewed. We selected 154 patients with both AIC and PID (n=17), or AIC alone (n=137) for inclusion in two cohorts. Immunoglobulin levels, vaccine titers, lymphocyte subsets (T, B and NK cells), autoantibodies, clinical characteristics, and response to treatment were recorded. Results: Clinical features associated with AIC-PID included splenomegaly, short stature, and recurrent or chronic infections. PID patients were more likely to have autoimmune hemolytic anemia (AIHA) or Evans syndrome than AIC-only patients. The AIC-PID group was also distinguished by low T cells (CD3 and CD8), low immunoglobulins (IgG and IgA), and higher prevalence of autoantibodies to red blood cells, platelets or neutrophils. AIC diagnosis preceded PID diagnosis by 3 years on average, except among those with partial DiGeorge syndrome. AIC-PID patients were more likely to fail first-line treatment. Conclusions: AIC patients, especially those with Evans syndrome or AIHA, should be evaluated for PID. Lymphocyte subsets and immune globulins serve as a rapid screen for underlying PID. Early detection of patients with comorbid PID and AIC may improve treatment outcomes. Prospective studies are needed to confirm the diagnostic clues identified and to guide targeted therapy.
KW - Evans syndrome
KW - anemia
KW - autoimmune cytopenia
KW - immune dysregulation
KW - neutropenia
KW - primary immunodeficiency
KW - thrombocytopenia
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U2 - 10.3389/fimmu.2021.649182
DO - 10.3389/fimmu.2021.649182
M3 - Article
C2 - 33968040
AN - SCOPUS:85105371288
SN - 1664-3224
VL - 12
JO - Frontiers in immunology
JF - Frontiers in immunology
M1 - 649182
ER -