Hidden noise in immunologic parameters might explain rapid progression in early-onset periodontitis

by George Papantonopoulos, Chryssa Delatola, Keiso Takahashi, Marja L. Laine, Bruno G. Loos

To investigate in datasets of immunologic parameters from early-onset and late-onset periodontitis patients (EOP and LOP), the existence of hidden random fluctuations (anomalies or noise), which may be the source for increased frequencies and longer periods of exacerbation, resulting in rapid progression in EOP. Principal component analysis (PCA) was applied on a dataset of 28 immunologic parameters and serum IgG titers against periodontal pathogens derived from 68 EOP and 43 LOP patients. After excluding the PCA parameters that explain the majority of variance in the datasets, i.e. the overall aberrant immune function, the remaining parameters of the residual subspace were analyzed by computing their sample entropy to detect possible anomalies. The performance of entropy anomaly detection was tested by using unsupervised clustering based on a log-likelihood distance yielding parameters with anomalies. An aggregate local outlier factor score (LOF) was used for a supervised classification of EOP and LOP. Entropy values on data for neutrophil chemotaxis, CD4, CD8, CD20 counts and serum IgG titer against Aggregatibacter actinomycetemcomitans indicated the existence of possible anomalies. Unsupervised clustering confirmed that the above parameters are possible sources of anomalies. LOF presented 94% sensitivity and 83% specificity in identifying EOP (87% sensitivity and 83% specificity in 10-fold cross-validation). Any generalization of the result should be performed with caution due to a relatively high false positive rate (17%). Random fluctuations in immunologic parameters from a sample of EOP and LOP patients were detected, suggesting that their existence may cause more frequently periods of disease activity, where the aberrant immune response in EOP patients result in the phenotype “rapid progression”.