Cryptosporidiosis in Ptients with Inborn Errors of Immunity: Retrospective cohort study of the French National Reference Center (CEREDIH).

Abstract

Inborn Errors of Immunity (IEI) display increased susceptibility to infections among which cryptosporidiosis is an opportunistic infection poorly characterized in this population. We report cases of Cryptosporidium spp. infections in French patients with IEI based on data from the registry of the French National Reference Center for IEI (CEREDIH). Patients diagnosed with an IEI between 1986 and 2025 and who experienced proven cryptosporidiosis were included. Of the 10,004 patients in the CEREDIH registry, 149 were identified with at least one episode of parasitic infection (≈1.4%). Forty-one patients (27.5%) had cryptosporidiosis (0.41% of the cohort) and had the following diagnoses: Combined immunodeficiency (CID, n=25 including 8 Hyper IgM (HIGM) syndromes, 9 other CID, 4 HLA class II deficiency), Hyper IgE syndrome (n=2), Diaphanous related formin 1 mutation (n=1), Signal transducer and activator of transcription 1 (STAT1) gain-of-function (GOF) (n=1), Activated PI3K-delta syndrome (n=6), Common variable immunodeficiency disorders (CVID, n=3) and 7 miscellaneous.. The male-to-female ratio was 1.92 and the mean age at onset of cryptosporidiosis was 16.6±17.5 years. Twenty (50%) patients had cholangitis and 23 (63%) had an indication for hematopoietic stem cell transplantation, which was performed in 15 (38%). Seventeen (41.5%) patients died. Cryptosporidiosis is a serious comorbidity in patients with IEI with a high mortality rate reaching more than one third of the patients. CID including HIGM syndrome and other CID were the most represented underlying condition in this study with the highest morbidity and mortality (cholangitis and its complications).