Childhood isolated C3d-positive AIHA: favorable prognosis but rare relapse or associated immunodeficiency
Year: 2025
Type: article
Study design: Observational Study
Abstract: ABSTRACT: Autoimmune hemolytic anemia (AIHA) with an isolated C3d+ direct antiglobulin test is a rare and understudied condition in children. It typically encompasses cold agglutinin syndrome and paroxysmal cold hemoglobinuria, both transient, infection-triggered disorders collectively referred to as cold AIHA. We report a national cohort of 142 pediatric patients with isolated C3d+ AIHA, representing 21.6% of all childhood AIHA cases enrolled in the French OBS'CEREVANCE cohort over a 32-year period. The median age at diagnosis was 3.2 years (male-to-female ratio, 1.3), and median follow-up was 2.8 years. Infectious symptoms were present in 63.4% of cases. At diagnosis, median hemoglobin was 6.4 g/dL; 69.7% of patients had inadequate reticulocytosis (bone marrow responsiveness index of <121), and 90.4% required transfusions. Eighteen patients (12.7%) had or developed immunopathological manifestations (IM) including 5 diagnosed with primary immunodeficiency (4 with autoimmune lymphoproliferative syndrome). Among 8 (5.6%) patients with relapsing disease, 6 had no IM at diagnosis but 4 developed IM at relapse. Nine patients were antinuclear antibodies (ANA) positive; none progressed to systemic lupus over a median follow-up of 4.9 years. Corticosteroids were administered to 82.4% of patients (median duration, 4.5 months), with no clear benefit over untreated patients regarding hospital stay or transfusion needs. No deaths were reported. In conclusion, pediatric isolated C3d+ AIHA generally follows a favorable course. However, a minority of patients may reveal underlying immune disorders, highlighting the importance of tailored evaluation at diagnosis. Cold agglutinin testing with thermal amplitude and Donath-Landsteiner testing, rarely performed in this cohort, warrant further study for their impact on diagnosis and clinical management.
Source: Blood Advances
Authors: Marion Blachez, Nathalie Aladjidi, Thomas Modot, Helder Fernandes, Nathalie Garnier, Pascal Chastagner, Sophie Bayart, Corinne Armari-Alla, Christophe Piguet, Marlène Pasquet, Catherine Paillard, Claire Pluchart, Corinne Guitton, Caroline Thomas, Vincent Barlogis, Isabelle Pellier, Jean-Louis Stephan, Joy Benadiba, Eric Jeziorski, Marianna Deparis, Liana Carausu, Nathalie Cheikh, Valérie Li-Thiao Te, Julien Lejeune, Aude Marie-Cardine, Frédéric Millot, Wadih Abou Chahla, Sophie Gay, Aurélia Alimi, Arnaud Petit, Martin Castelle, Despina Moshous, Capucine Picard, Frédéric Rieux-Laucat, Thierry Leblanc, Stéphane Ducassou, Guy Leverger, Mony Fahd, Sébastien Héritier
Institutions: Hôpital Saint- Camille, Inserm, Centre Hospitalier Universitaire de Bordeaux, Centre d'Investigation Clinique Plurithématique de Bordeaux, Hôpital Saint-Antoine, Établissement Français du Sang, Hospices Civils de Lyon, Centre Hospitalier Régional et Universitaire de Nancy, Hôpital d'Enfants, Centre Hospitalier Universitaire de Rennes, Centre Hospitalier Universitaire de Grenoble, Centre Hospitalier Universitaire de Limoges, Centre Hospitalier Universitaire de Toulouse, Hôpital Purpan, Hôpital d'Hautepierre, Centre Hospitalier Universitaire de Reims, Assistance Publique – Hôpitaux de Paris, Bicêtre Hospital, Centre Hospitalier Universitaire de Nantes, Assistance Publique Hôpitaux de Marseille, Hôpital de la Timone, Centre National de la Recherche Scientifique, Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes Angers, Centre Hospitalier Universitaire d'Angers, Université d'Angers, Centre Hospitalier Universitaire de Saint-Étienne, Université Jean Monnet, Centre Hospitalier Universitaire de Nice, Centre Hospitalier Universitaire de Montpellier, Hôpital Arnaud de Villeneuve, Centre Hospitalier Universitaire de Caen Normandie, Centre Hospitalier Régional Universitaire de Brest, Centre Hospitalier Universitaire de Besançon, Centre Hospitalier Universitaire Amiens-Picardie, Université de Tours, Centre Hospitalier Universitaire de Tours, Centre Hospitalier Universitaire de Rouen, Université de Poitiers, Centre Hospitalier Universitaire de Poitiers, Centre Hospitalier Universitaire de Lille, Hôpital Jeanne de Flandre, Sorbonne Université, Hôpital Armand-Trousseau, Centre de Recherche Saint-Antoine, Hôpital Necker-Enfants Malades, Université Paris Cité, Institut des Maladies Génétiques Imagine, Hôpital Robert-Debré
Language: English
Topic: Blood groups and transfusion
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,800
OpenAlex ID: W4415395861