The problem of hypersensitivity to vitamin preparations

ABSTRACT. The problem of the development of adverse reactions as a result of the use of diagnostic and medicinal products (drugs) is becoming increasingly important. Patients more often report reactions to local anesthetics (43.2 % of cases), antibiotics (18.8 %), nonsteroidal anti-inflammatory drugs (9.7 %), other drugs (28.4 %), B vitamins (4-5 %). It is important to understand that hypersensitivity (HS) to vitamin preparations (VP) is very common, according to patients, but not so often confirmed by their in-depth allergy examination. Basic data on HS before the VP were obtained in the 80-90s of the 20th century, but since then the situation has changed radically. The frequency of HS on these drugs is based on medical history when patients use multicomponent VP for oral administration, allergens in which may be other components (shell tablets and capsules, metal salts, flavors, sweeteners, dyes, preservatives). The causative allergens in the injectable forms of VP can also be auxiliary ingredients of the drug, in particular lidocaine and benzyl alcohol. There are only a few scientific publications with the appropriate evidence base for HS to individual VP, more often B vitamins. The clinical picture of HS reactions to VP is diverse (systemic, cutaneous, respiratory, rarely other visceral manifestations). They can develop both immediately and in a delayed type. Part of the VP (B vitamins, vitamin K) can cause the development of anaphylaxis with fatal consequences. VP, as a rule, do not belong to vital drugs therefore it is possible for this reason till now in real clinical practice insufficiently developed methods of allergodiagnostics both in vivo (skin, provocative tests), and in vitro (laboratory tests) among patients with suspicion for the development of HS to VP. It is not possible to perform allergy diagnostics in persons who have taken complex VP, so there is a problem of hyperdiagnosis of drug allergy to them. Therefore, the problem of determining the true allergic reaction in patients who report the development of a history of HS to VP remains relevant. As a rule, after the development of any adverse reaction during the reception of VP on the patient hangs the label “allergy to vitamins” for life without further allergy examination. That is why the problem of HS to VP needs further study.

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.

New technologies in molecular allergodiagnostics

The article presents the characteristics of the ALEX2 (MacroArrayDX, Wien, Austria). It is designed for simultaneous detection of IgE total and specific IgE-aB to 120 extracts and 180 molecules by solid-phase enzyme immunoassay. Extracts and allergen molecules combined with nano-particles are sorbed on a solid-phase substrate, forming a macroscopic multiplex matrix - the immune allergy chip. The Institute of Clinical and Laboratory Standards (CLSI) conducted research on the verification and validation of the ALEX2 in relation to the ImmunoCAP macroarray test system (ThermoFisher Scientific, Uppsala, Sweden), which is often used in allergodiagnostics. The results obtained on the two test systems were comparable. One of the most important features of the ALEX2 test system is that unique allergen molecules and allergenic extracts are included in its composition, and a method has been found to inhibit cross-reactive hydrocarbon determinants (CCDs), which cause frequent non-specific binding of IgE-aT. The use of this test system makes it possible to carry out component allergy diagnostics with the determine of the dominant sensitizing factor in cases of mono- and polyvalent sensitization. The test results affect the determination of indications and the effectiveness of ASIT, allow assessing the risk of anaphylaxis and predicting further treatment tactics for the patient.

Crystal structure of timothy grass allergen Phl p 12.0101 reveals an unusual profilin dimer

Timothy grass pollen is a source of potent allergens. Among them, Phl p 1 and Phl p 5 are thought to be the most important, as a majority of timothy grass-allergic individuals have IgE antibodies directed against these two allergens. The profilin from timothy grass (Phl p 12) has been registered as a minor allergen, with up to 35% of individuals in populations of grass pollen allergic patients showing IgE binding to Phl p 12. Profilins are primarily minor allergens and are known for a high likelihood of co-sensitization as well as cross-reactivity situations caused by their sequence and structure similarity. The crystal structure of Phl p 12.0101 was determined and it revealed that this allergen may form an unusual dimer not previously observed among any profilins. For example, the Phl p 12 dimer has a completely different geometry and interface when compared with the latex profilin (Hev b 8) dimer that has its crystal structure determined. The structure of Phl p 12.0101 is described in the context of allergenic sensitization and allergy diagnostics. Moreover, the structure of the Phl p 12.0101 dimer is discussed, taking into account the production of recombinant allergens and their storage.