*2.3. Immunogenetics*

High-resolution genotyping of Human Leukocyte Antigen (HLA) class I (A, B and C) and II (DRB1 and DQB1) loci was performed using the LABType sequence-specific oligonucleotide typing test (One Lambda, Canoga Park, CA, USA). DNA whole blood isolation was carried out with the QIAMP DNA Blood Mini Kit, following the manufacturer's instructions (Qiagen, Hilden, Germany). Target DNA was amplified by PCR using sequence-specific primers, followed by hybridization with allele-specific oligodeoxynucleotides coupled with fluorescent phycoerythrin-labelled microspheres. Fluorescence intensity was determined using a LABScan 100 system (Luminex xMAP, Austin, TX, USA). HLA alleles were assigned using the HLA-Fusion software (One Lambda, Canoga Park, CA, USA).

We also performed a clinical exome analysis based on Next-Generation Sequencing (NGS) that covers the coding regions of 4490 genes with clinical significance (SOPHiA Clinical Exome Solution, Lausanne, Switzerland), and analyzed 237 genes associated with primary immunodeficiencies (Supplementary Material S1). Sequencing was carried out on the NextSeq 1000 platform (Illumina, San Diego, CA, USA), and the results were analyzed with DDM v.5.8.0.3 program of Sophia Genetics and the IGV informatic application (Integrative Genomics Viewer). The reference genome sequence used in the alignment phase corresponds to the GRCh37/hg19 (UCSC) version. Bioinformatic predictors (Mutation-Taster and CADD) were used to evaluate the pathogenicity of the variants found. Genetic variants found were confirmed by Sanger sequencing.

## *2.4. Microbiology Giardia Infection Diagnosis*

*Giardia* infection was diagnosed using antigen detection by immunochromatography (Rida Quick Cryptosporidium/Giardia/Entamoeba, R-Biopharm AG, Darmstadt, Germany), by microscopic observation of cysts in stool samples or by molecular diagnosis (FilmArray Gastrointestinal Panel, bioMérieux, Marcy l'Étoile, France).
