COMPONENT ALLERGY DIAGNOSTICS AS A TOOL FOR THEMANAGEMENT OF PATIENTS WITH ALLERGIC DISEASES

Molecular diagnostics makes it possible to determine true and cross reactivity differentially, which is of great clinical importance not only for the diagnosis of the true spectrum of sensitization, but also for the reasonable choice of pathogenetic therapy, prediction of the effectiveness and risks associated with allergenspecific immunotherapy. A number of clinical cases are presented as examples demonstrating the clarifying nature of molecular allergodiagnostics.

Tumor microenvironment has clinical significance in terms of prognosis and therapy prediction

At this point, the tumor microenvironment (TME) clinical significance in terms of prognosis and therapy prediction has become obvious. The TME is comprised of a varied population of cytokine/chemokine-releasing cells, which results in a local immune response. Colorectal cancer cells also produce antigens that are responsible for initiating an antitumor response. A better clinical prognosis is linked to a large number of effector T cells, which are predominantly made up of CD8+ CTLs, and a low concentration of regulatory T cells. Concentration of PD-L1 and its mutation load are both predictors of a response to anti-PD-L1 treatment. Despite ICI clinical trials showing that ICIs work, patients' responses to ICIs differ depending on the indication. With the emergence of TME-based biomarkers, we will demand additional TME-based biomarkers for more accurate therapies. The spatial-temporal interaction of immune system cells will also need to be investigated, in addition to current test criteria such as the identification of somatic changes, measurement of TMB, loss of HLA locus, and assessment of PD-L1 expression. Also, in order to accurately identify ICI therapy's most favorable recipients, identifying patients who will most benefit from ICI therapy solely or in combination with other treatment modalities is crucial.

IHRW: An Improved Hypergraph Random Walk Model for Predicting Three-Drug Therapy

Drug combination therapy is a well-established concept in the treatment of complex diseases due to its fewer side effects, lower toxicity, and better efficacy. However, it is challenging to identify efficacious drug combinations from many drug candidates. Computational models could greatly reduce the cost, but most models did not use data for more than two-drug combinations and could not predict three-drug therapy. However, three-drug combinations account for about 21% of the known combinations, which is a very important type of treatment. Here, we utilized higher-order information and developed an improved hypergraph random walk model (IHRW) for three-drug therapy prediction. This is the first method to explore the combination of three drugs.As a result, the case studies of breast cancer, lung cancer, and colon cancer showed that IHRW had a powerful ability to predict potential efficacious three-drug combinations, which provides new prospects for complex disease treatment. The code of IHRW is freely available at https://github.com/wangqi27/IHRW.

A circulating, disease-specific, mechanism-linked biomarker for ATTR polyneuropathy diagnosis and response to therapy prediction

The transthyretin (TTR) amyloidoses (ATTR) are progressive, degenerative diseases resulting from dissociation of the TTR tetramer to monomers, which subsequently misfold and aggregate, forming a spectrum of aggregate structures including oligomers and amyloid fibrils. To determine whether circulating nonnative TTR (NNTTR) levels correlate with the clinical status of patients with V30M TTR familial amyloid polyneuropathy (FAP), we quantified plasma NNTTR using a newly developed sandwich enzyme-linked immunosorbent assay. The assay detected significant plasma levels of NNTTR in most presymptomatic V30M TTR carriers and in all FAP patients. NNTTR was not detected in age-matched control plasmas or in subjects with other peripheral neuropathies, suggesting NNTTR can be useful in diagnosing FAP. NNTTR levels were substantially reduced in patients receiving approved FAP disease-modifying therapies (e.g., the TTR stabilizer tafamidis, 20 mg once daily). This NNTTR decrease was seen in both the responders (average reduction 56.4 ± 4.2%; n = 49) and nonresponders (average reduction of 63.3 ± 4.8%; n = 32) at 12 mo posttreatment. Notably, high pretreatment NNTTR levels were associated with a significantly lower likelihood of clinical response to tafamidis. Our data suggest that NNTTR is a disease driver whose reduction is sufficient to ameliorate FAP so long as pretreatment NNTTR levels are below a critical clinical threshold.