Details

Autor(en) / Beteiligte

• Palmblad, Jan
• Sohlberg, Ebba
• Nilsson, Christer C.
• Lindqvist, Henric
• Deneberg, Stefan
• Ratcliffe, Paul
• Meinke, Stephan
• Mörtberg, Anette
• Klimkowska, Monika
• Höglund, Petter

Titel

Clinical and immunological features in ACKR1/DARC-associated neutropenia

Ist Teil von

• Blood advances, 2024-02, Vol.8 (3), p.571-580

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2024

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• •Subjects with ADAN may show neutrophil counts similar to those with SCNP, complicating differential diagnoses.•Differentially expressed cytokines and higher nonclassical monocyte and antineutrophil antibody numbers suggest immune dysregulation in ADAN. [Display omitted] ACKR1/DARC-associated neutropenia (NP; ADAN; Online Mendelian Inheritance in Man 611862), caused by a variation in the ACKR1/DARC gene (rs2814778), is common in persons of African or Middle Eastern descent. In a cohort of 66 genetically confirmed subjects with ADAN, we show that absolute neutrophil counts (ANCs) may occasionally be lower than previously recognized (0.1 × 109-0.49 × 109/L for 9% of the subjects), which is similar to ANCs in severe congenital NP (SCNP). ANCs often normalized during inflammation, even mild. Individuals with ADAN (of 327 observed person-years) showed no cases of myelodysplastic syndrome (MDS), which is frequently encountered in SCNP. Unexpectedly, 22% presented with autoantibodies to neutrophils, compared with <1% in controls. Compared with healthy donors, subjects with ADAN demonstrated significantly lower human cationic antimicrobial protein-18/pro-leucin leucin-37 plasma levels; higher levels of nonclassical, proinflammatory, 6-sulfo LacNac-expressing monocytes; and differentially expressed plasma levels of 28 of the 239 analyzed cytokines related to immunity/inflammation, cell signaling, neutrophil activation, and angiogenesis. Collectively, more severe neutropenia in ADAN than previously assumed may complicate differential diagnoses compared with other SCNPs, and various (auto)immune/inflammatory reactions with a distinct profile may be a cause or consequence of this hereditary neutropenia.