Systematic Classification of Primary Immunodeficiencies Based on Clinical, Pathological, and Laboratory Parameters

Abstract

The classification of diseases has several important applications ranging from diagnosis and choice of treatment to demographics. To date, classifications have been successfully created manually, often within international consortia. Some groups of diseases, such as primary immunodeficiencies (PIDs), are especially hard to nosologically cluster due, on one hand, to the presence of a wide variety of disorders and, in contrast, because of overlapping characteristics. More than 200 PIDs affecting components of the innate and adaptive immune systems have been described. Clinical, pathological, and laboratory characteristics were collected and used to group PIDs. A consensus of at least five independent methods provided a novel classification of 11 groups, which revealed previously unknown features and relationships of PIDs. Comparison of the classification to independent features, including the severity and therapy of the diseases, functional classification of proteins, and network vulnerability, indicated a strong statistical support. The method can be applied to any group of diseases.

How to Define Pathogenicity, Health, and Disease?

“…One application would be in classification and nosology of related diseases [Samarghitean et al. ; Fava et al. ].…”

Examining the Use of ICD-9 Diagnosis Codes for Primary Immune Deficiency Diseases in New York State

“…Excluding IgA deficiency as the most common but often asymptomatic defect, a textbook estimate of incidence is about 1:10,000 persons [5, 6], but this could be an underestimate, as suggested by a recent household survey [7]. While most patients have recurrent bacterial, viral or fungal infections, systemic symptoms such as fever, weight loss, and failure to thrive, immune defects often lead to other complications, including autoimmune diseases, inflammatory conditions, organ dysfunction, and cancer, especially lymphoma [1, 3, 8, 9]. Perhaps due to different ages of onset and varied disease manifestations, patients are likely to receive care in a number of medical venues while the underlying immune defect remains unrecognized.…”

Simulation of the dynamics of primary immunodeficiencies in CD4+ T-cells

“…Due to the large number, rarity and overlapping symptoms of PIDs, the diagnosis may be late, difficult and costly. Several efforts have been made to ease diagnosis by classifying PIDs [9, 10], predicting and prioritizing candidate genes and proteins [35–38]. The FBLs of our model and the PID-perturbed attractors from simulations provide information about proteins that affect several pathways and could be involved with PIDs.…”

“…Several classification schemes have been made, including the frequently updated classification by the International Union of Immunological Societies (IUIS) expert committee for PIDs [9]. PIDs have also been classified with a network approach that clusters the diseases based on signs, symptoms and laboratory parameters [10]. The severity of PIDs ranges from mild to moderate, and severe to lethal.…”