Background and Aims

Primary antibody deficient (PAD-)patients form a heterogeneous group -clinically, immunologically as well as genetically- ranging from milder (e.g. IgG-subclass deficiency) to severe (e.g. X-linked agammaglobulinemia) disease. PAD-patients suffer from recurrent infections but may also have autoimmune and lymphoproliferative comorbidities. There is insufficient consensus about PAD-subgroup diagnoses (e.g. CVID-definition); often the genetic background has not been elucidated. A standardized description of PAD-phenotypes is lacking. All this impairs the formation of homogeneous PAD-patient cohorts.

The Human Phenotype Ontology (HPO) immune mediated disorders consortium is therefore re-evaluating and completing the PAD-related HPO-terms to allow efficient data exchange and matching of phenotypically similar PAD-patients for future research.

Methods

After a first meeting regarding goal and methods of the HPO-consortium, subgroups related to different primary immunodeficiency (PID-)categories were started to define PID-relevant terminology using the HPO-website, literature, and ESID, IUIS and OMIM classifications.

Results

As a principle, it was decided to build the PAD-related HPO-tree based on as unambiguously interpretable items as possible only, thereby avoiding the ongoing variance in PAD-subgroup definitions. E.g., ‘hypogammaglobulinemia’ was deleted as HPO-term, and replaced by separate HPO-terms such as ‘decreased total IgG (or IgA or IgM) in blood’, subdivided in ‘transient’ vs. ‘chronic’, and ‘(near) absent’ vs. ‘partially decreased’. (The full new PAD-related HPO-tree will be shown during the meeting.)

Conclusions

The PID-related HPO-consortium has set out to improve classification of heterogeneous PAD diseases for research purposes through an accurate and less ambiguous description of the phenotypes. Once accepted, this PAD-related HPO-tree will empower future multicenter clinical research and related genetic discoveries.