Longitudinal follow-up of autoimmune neutropenia in adults—a single-cohort experience
5 affiliations
- 1Clinical Immunology, Allergy and Urticaria Institute, Sheba Medical Center
- 2The Gray Faculty of Medical and Health Science
- 3National Hemophilia Center, Sheba Medical Center
- 4Blood Bank and Platelet Immunology Laboratories
- 5Ruth and Bruce Rappaport Faculty of Medicine, Technion
Abstract
Introduction: Adult autoimmune neutropenia (AIN) is a rare and probably underrecognized immune cytopenia for which population-based adult incidence estimates are not established. Unlike the benign, self-limiting course seen in children, the adult trajectory is poorly defined. We evaluated its presentation, course, and the factors associated with the requirement for treatment.
Methods: Retrospective study of adults with neutropenia (ANC <1,500/µL) and anti-neutrophil antibodies on granulocyte immunofluorescence testing (GIFT) at a tertiary center, 2015–2025. GIFT positivity was considered supportive, not sufficient. Two patients later found to have a clonal disorder were described but excluded from outcome analyses.
Results: A total of 41 patients were included (87.8% female; mean age 32.3 ± 14.8 years, followed 7.0 ± 7.1 years). A systemic immune disorder was present in 23 (56.1%): autoimmunity in 21 (51.2%), inborn errors of immunity in 6 (15.0%). Of 39 patients analyzed for outcome, 18 (46.2%) required neutropenia-directed therapy. These presented more often with fever (38.9% vs 4.8%, p=0.015) and thrombocytopenia (50.0% vs 14.3%, p=0.035), had lower platelet nadirs (p=0.024), and were admitted for neutropenic fever more often (3.6 vs 0.3 admissions, p=0.005). Malignancy (12.8%) and death (5.1%) occurred almost exclusively in this group, although neither difference was significant. Both nadirs were associated with the requirement for therapy (AUC 0.807).
Conclusions: Adult AIN is heterogeneous and frequently marks broader immune dysregulation. A substantial subgroup carries a real burden of neutropenic fever and hospitalization, identifiable at presentation by the depth of both nadirs. AIN in an adult warrants a structured immunological evaluation and risk-adapted follow-up.
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BibTeX
@article{niznik2026longitudinal,
title = {{Longitudinal follow-up of autoimmune neutropenia in adults—a single-cohort experience}},
author = {Stanley Niznik and Shirley Frizinsky and Soad Hag Yehia and Ronen Shavit and Shiri Weinstein and Mudi Misgav and Lilach Bonstein and Nancy Agmon-Levin},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1956807},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1956807/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Longitudinal follow-up of autoimmune neutropenia in adults—a single-cohort experience
AU - Stanley Niznik
AU - Shirley Frizinsky
AU - Soad Hag Yehia
AU - Ronen Shavit
AU - Shiri Weinstein
AU - Mudi Misgav
AU - Lilach Bonstein
AU - Nancy Agmon-Levin
PY - 2026
DA - 2026/10/08
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1956807
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1956807/full
AB - Introduction: Adult autoimmune neutropenia (AIN) is a rare and probably underrecognized immune cytopenia for which population-based adult incidence estimates are not established. Unlike the benign, self-limiting course seen in children, the adult trajectory is poorly defined. We evaluated its presentation, course, and the factors associated with the requirement for treatment. Methods: Retrospective study of adults with neutropenia (ANC <1,500/µL) and anti-neutrophil antibodies on granulocyte immunofluorescence testing (GIFT) at a tertiary center, 2015–2025. GIFT positivity was considered supportive, not sufficient. Two patients later found to have a clonal disorder were described but excluded from outcome analyses. Results: A total of 41 patients were included (87.8% female; mean age 32.3 ± 14.8 years, followed 7.0 ± 7.1 years). A systemic immune disorder was present in 23 (56.1%): autoimmunity in 21 (51.2%), inborn errors of immunity in 6 (15.0%). Of 39 patients analyzed for outcome, 18 (46.2%) required neutropenia-directed therapy. These presented more often with fever (38.9% vs 4.8%, p=0.015) and thrombocytopenia (50.0% vs 14.3%, p=0.035), had lower platelet nadirs (p=0.024), and were admitted for neutropenic fever more often (3.6 vs 0.3 admissions, p=0.005). Malignancy (12.8%) and death (5.1%) occurred almost exclusively in this group, although neither difference was significant. Both nadirs were associated with the requirement for therapy (AUC 0.807). Conclusions: Adult AIN is heterogeneous and frequently marks broader immune dysregulation. A substantial subgroup carries a real burden of neutropenic fever and hospitalization, identifiable at presentation by the depth of both nadirs. AIN in an adult warrants a structured immunological evaluation and risk-adapted follow-up.
SN - 1664-3224
ER -