Childhood Allergy Disease, Early Diagnosis, and the Potential of Salivary Protein Biomarkers.

Allergic disease has risen to epidemic proportions since the last decade and is among the most common noncommunicable, chronic diseases in children and adolescents worldwide. Allergic disease usually occurs in early life; thus, early biomarkers of allergic susceptibility are required for preventive measures to high-risk infants which enable early interventions to decrease allergic severity. However, to date, there is no reliable general or specific allergy phenotype detection method that is easy and noninvasive for children. Most reported allergic phenotype detection methods are invasive, such as the skin prick test (SPT), oral food challenge (OFC), and blood test, and many involve not readily accessible biological samples, such as cord blood (CB), maternal blood, or newborn vernix. Saliva is a biological sample that has great potential as a biomarker measurement as it consists of an abundance of biomarkers, such as genetic material and proteins. It is easily accessible, noninvasive, collected via a painless procedure, and an easy bedside screening for real-time measurement of the ongoing human physiological system. All these advantages emphasise saliva as a very promising diagnostic candidate for the detection and monitoring of disease biomarkers, especially in children. Furthermore, protein biomarkers have the advantages as modifiable influencing factors rather than genetic and epigenetic factors that are mostly nonmodifiable factors for allergic disease susceptibility in childhood. Saliva has great potential to replace serum as a biological fluid biomarker in diagnosing clinical allergy. However, to date, saliva is not considered as an established medically acceptable biomarker. This review considers whether the saliva could be suitable biological samples for early detection of allergic risk. Such tools may be used as justification for targeted interventions in early childhood for disease prevention and assisting in reducing morbidity and mortality caused by childhood allergy.

Inhibition of Activin A suppressed tumor necrosis factor-α secretion and improved histopathological conditions in malarial mice.

Malaria infection still remains as one of the most prominent parasitic diseases afflicting mankind in tropical and subtropical regions. The severity of malaria infection has often been associated to exuberant host immune inflammatory responses that could possibly lead to severe immunopathological conditions and subsequent death of host tissues. Activin A is a protein belonging to the transforming growth factor-beta (TGF-ß) family that regulates multiple physiological processes and pathological-associated diseases. The biological roles of activin A have been associated with manipulation of inflammation-related processes and modulation of host immune responses. This implies that activin A protein could play a role in malaria pathogenesis since malaria infection has been closely linked to severe immune responses leading to death, However, the actual in vivo role of activin A in malaria infection remains elusive. Hence, this study was undertaken to investigate the involvement of activin A in malaria infection as well as to assess the modulating effects of activin A on the cytokine releases (TNF-α, IFN-γ and IL-10) and histopathological changes in major affected organs (kidney, liver, lung, brain and spleen) in malarial mice infected with Plasmodium berghei ANKA. Our results showed that the concentrations of plasma activin A were significantly increased in malarial mice throughout the study periods. Also. the systemic activin A level was positively correlated with malaria parasitemia. This indicates that activin A could play a role in malaria pathogenesis and malaria parasitemia development. Plasma TNF-α, IFN-γ and IL-10 cytokine levels were significantly increased in malarial mice at day-5 post infection, suggesting that these cytokines attributed to severe malaria pathogenesis. Histopathological features such as sequestration of parasitized red blood cells (pRBCs) and hemozoin formation were amongst the most common pathological conditions observed in tissues of major affected organs (kidney, liver, lung, brain and spleen) in malarial mice. Neutralization of activin A production via recombinant mouse activin RIIA Fc chimera (rmActivin RIIA Fc chimera) had significantly reduced the parasitemia levels in malarial mice. The release of TNF-α cytokine was significantly reduced as well as the sequestration of parasitized pRBCs and hemozoin formation in major affected organs in malarial mice were also alleviated following inhibition of activin A production. Overall, this preliminary study suggests that activin A could play an immune modulation role in malaria pathogenesis through modulation of TNF-α release that benefits host from severe pathological destructions provoked by intensified inflammatory responses. Further studies are warranted to elucidate the precise mechanism of immune modulation mediated by activin A and its associated immune-modulation mediators in regulating the inflammatory responses elicited during the course of malaria infection.