Construction and Clinical Validation of a Questionnaire-based Risk Score to Identify Patients Suffering from Immunodeficiency or Systemic Autoimmunity

Abstract

Aims: A self-reporting tool for identifying adults at risk for immune-based diseases was designed and termed immune system assessment questionnaire (ISAQ). It was the aim of this study to validate this novel questionnaire in groups of patients with defined immunodeficiency or autoimmune diseases in comparison to normal adults. Study Design: Non-randomised, cross-sectional observational study in groups of patients and normal adults. Place and Duration of Study: Department of Rheumatology and Clinical Immunology and Clinical Epidemiology Group, Institute of Medical Biometry and Medical Informatics University Medical Center Freiburg, Germany. Questionnaires from patients and controls were collected between March 2005 and November 2010. Methodology: Two experienced clinical immunologists selected 17 informative topics including frequency and duration of infections, previous surgery on immunological organs, recent polytrauma, vaccination history, allergies, co-morbidities, use of antibiotics and immunomodulating agents. The ensuing questions were differently weighted based on published evidence and assumed relevance for immunological dysfunction. The questionnaire was distributed to 539 cases suffering from chronic immunodeficiency (n=322) or autoimmunity (n=217) and to 1020 healthy controls. An ISAQ score was calculated for each participant based on the sum of the weighted items. Results: The median ISAQ-score was 39.5 for cases and 30.4 for controls. 93.7% of all controls scored lower than the median of the cases, which resulted in an AUC of the ROC curve of 0.838 (95%CI: 0.817-0.859). Items with highest predictive value were frequency and duration of infections, use of antibiotics, corticosteroids, immunosuppressants, sinus-mucosa resection, chronic disease of kidney, lungs, gut and hematopoietic system. Although the results indicate that neither the item selection nor the weighting of single items were optimal, several sub-scores with reduced item number could not substitute for the whole ISAQ. Conclusion: The ISAQ can discriminate between healthy individuals and persons suffering from immune-based disease. The ISAQ performs better for chronic immunodeficiency than for chronic rheumatic diseases; the highest values were obtained for common variable immunodeficiency (CVID) and systemic vasculitides. Future studies are needed to refine item selection and validate the score for predicting immune dysfunction.