Rajica Stosovic

@med.bg.ac.rs

Assistant professor at Allergology and Clinical Immunology Department, Medical faculty University of Belgrade
Medical faculty University of Belgrade

Rajica Stosovic


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https://researchid.co/rajicastosovic

RESEARCH, TEACHING, or OTHER INTERESTS

Immunology, Pulmonary and Respiratory Medicine
20

Scopus Publications

Scopus Publications

  • Systemic Allergic Reactions to Subcutaneous Allergen Immunotherapy—A Single-Center Experience
    Nataša Kusić, Aleksandra Plavšić, Vojislav Đurić, Jasna Bolpačić, Rajica Stošović, et al.
    Life, 2025
    Background: Allergen immunotherapy (AIT) is generally considered a safe treatment modality, with systemic reactions (SRs) representing its most significant adverse events, despite their low incidence. This study aimed to evaluate the frequency and characteristics of SRs associated with subcutaneous allergen immunotherapy (SCIT) and to identify potential risk factors. Methods: We conducted a retrospective analysis of 47,982 SCIT injections administered to 317 patients over 468 SCIT courses between January 2019 and January 2024. The study population consisted of 26 patients diagnosed with allergic rhinitis sensitized to pollen and/or house dust mites (HDMs), as well as individuals with venom allergies who experienced SRs to SCIT during the study period. Data collected included demographic characteristics, presence of asthma, allergen sensitivities, immunoglobulin E (IgE)-related immunologic biomarkers, and adverse reactions. SRs were classified according to the World Allergy Organization (WAO) SCIT SR Grading System. Results: A total of 26 SCIT-related SRs were documented in 26 patients (57.7% female; mean age 37.3 ± 10.04 years), corresponding to an incidence rate of 0.05% per injection, and 8.2% per patient. Asthma was present in 42.3% of patients. Prior adverse reactions to SCIT were noted in eight patients (30.8%). SRs occurred during the build-up phase in 61.5% of cases, compared with the maintenance phase. In 46.2% of patients, a single allergen was administered, while 53.8% received multiple allergens. Based on the WAO grading system, 30.8% of SRs were classified as grade 1, 42.3% as grade 2, 15.4% as grade 3, and 11.5% as grade 4. No fatalities were reported. The majority of SRs were early onset (88.5%), and epinephrine was administered in 76.9% of the cases. A higher serum specific IgE to total IgE (sIgE/tIgE) ratio was significantly associated with more severe SRs. Conversely, a history of prior allergic reactions to SCIT appeared to correlate with milder SRs. Conclusions: Our findings confirm that SRs to SCIT are rare, and severe reactions are infrequent. A higher serum sIgE/tIgE ratio can be risk factor for severe SRs. Nonetheless, a thorough risk–benefit assessment is essential prior to initiating SCIT, particularly in patients with identified risk factors.
  • Allergen immunotherapy adverse events in adults with respiratory allergies-data from ADER: An EAACI task force report
    Julijana Asllani, Dimitrios Mitsias, George Konstantinou, Etleva Qirko, Mirela Hitaj, et al.
    Allergy European Journal of Allergy and Clinical Immunology, 2025
    BackgroundRegistries can yield important insights on allergen immunotherapy (AIT) outcomes in daily clinical practice. However, systematic recordings of adverse events (AE) due to AIT in real‐life are lacking.MethodsThe Allergen Immunotherapy Adverse Events Registry (ADER) is a prospective, multicenter registry on real‐life AIT safety. Data on adults (>18 years old) with respiratory allergies receiving AIT with mites, pollens, epithelia, and/or molds were retrieved and analyzed from ADER. The frequency, characteristics and risk factors of AE were investigated. The MedDRA terminology was used to record AE.ResultsA total of 1545 individuals with a mean age of 33 ± 10 years receiving 1815 AIT courses (n = 1060 sublingual (SLIT); n = 755 subcutaneous (SCIT)) in centers from eight countries were included. Patients had allergic rhinitis (65%) or, asthma only (3.7%) or rhinitis with asthma (31.2%). Grass was the most frequent specific sensitizer (60.7%), followed by mites (45.5%), birch pollen (20.6%), epithelia (16.1%), and molds (8%). There were 296 AE recorded in 115 patients (7.4%). A higher frequency of AE occurred during up‐dosing (59%) compared to maintenance. Severe reactions were rare (0.2%), all in the context of SCIT. After 6 weeks of maintenance only one moderate AE was recorded. The most frequently reported symptoms were from the respiratory system and the skin. Having asthma, doing SCIT, AIT with mugwort, cat, or birch were associated with higher risk for AE while the use of allergoids induced lower risk.ConclusionIn real life clinical practice, AIT‐associated AE occur in a minority of patients, while severe reactions are rare. The presence of asthma and use of SCIT are risk factors, while the use of modified allergens lowers the risk.
  • The Allergen Immunotherapy Adverse Events Registry: Setup & methodology of a European Academy of Allergy and Clinical Immunology taskforce project
    Julijana Asllani, Dimitrios Mitsias, George Konstantinou, Alfred Priftanji, Mehmet Hoxha, et al.
    Clinical and Translational Allergy, 2023
    To the Editor, Over the last decades, systematic reviews and meta analyses of multiple double‐blind randomized placebo‐controlled trials have demonstrated the efficacy and safety of both subcutaneous (SCIT) and sublingual (SLIT) allergen immunotherapy (AIT) for respiratory and insect venom allergy. However, there is a wide range of AIT preparations used around the globe, and AEs are not always uniformly recorded, limiting the capability to draw safe conclusions or compare reports. Though various clinical development programs have generated substantial knowledge on different AIT preparations, they have been conducted in pre‐defined clinical conditions, not reflecting real‐life and therefore the results may not have generalized applicability. Very few pragmatic trials and observational studies have evaluated AIT safety in real‐life. Indicatively, Calderon et al. reported a total of 109 systemic reactions (SR) due to AIT recorded in 4316 patients in a prospective, longitudinal, “real‐life” web‐based survey. Another prospective study on SCIT safety in 581 patients reported immediate SR in 2.2%, delayed (7.4%), immediate local reactions (LR) (54.6%), while delayed in 56.1%. Recently, the Respiratory Effectiveness Group highlighted the role of real‐world evidence (RWE) in (i) filling knowledge gaps, (ii) extending the implementation of findings from Randomized controlled trials in heterogeneous populations or healthcare systems, and (iii) providing evidence to generate clinical practice guidelines. Prospective, systematic RWE from registries are considered to provide a broadly applicable source of knowledge compared with retrospective approaches. However, there is still a lack of such registries in the allergy field. In this context, a new hierarchy of AIT RWE that ranks pragmatic trials and registry data at the highest level of evidence was proposed in a recent European Academy of Allergy and Clinical Immunology (EAACI) position paper. Considering these factors, a Task Force (TF) was created under the academic support of EAACI to develop an AIT Adverse Events Registry (ADER). 1 | METHODOLOGY
  • Adverse events in children and adolescents undergoing allergen immunotherapy for respiratory allergies—Report from the Allergen Immunotherapy Adverse Events Registry (ADER), a European Academy of Allergy and Clinical Immunology taskforce
    Julijana Asllani, Dimitrios Mitsias, George Konstantinou, Eris Mesonjesi, Fatmira Xhixha, et al.
    Clinical and Translational Allergy, 2023
    BackgroundAlthough it has been shown that allergen immunotherapy (AIT) is well‐tolerated in children, systematic and prospective surveillance of AIT safety in real life settings is needed.MethodsThe multinational Allergen Immunotherapy Adverse Events Registry (ADER) was designed to address AIT safety in real life clinical practice. Data on children ≤18 years old with respiratory allergies undergoing AIT were retrieved. Patient‐ and AIT‐related features were collected and analyzed. The characteristics of adverse events (AE) and risk factors were evaluated.ResultsA total of 851 patients, 11.3 ± 3.4 years old, with rhinitis only (47.6%); asthma and rhinitis (44.5%); asthma (7.9%), receiving 998 AIT courses were analyzed. Sublingual immunotherapy (SLIT) accounted for 51% of the courses. In 84.5% of patients only one AIT treatment was prescribed. Pollen was the most frequent sensitizer (57.1%), followed by mites (53.4%), molds (18.2%) and epithelia (16.7%). Local and systemic AEs were reported in 85 patients (9.9%). Most AEs (83.1%) were mild and occurred in <30 min (87%). Respiratory and cutaneous symptoms were more frequent. Only 4 patients (0.47%) had severe AE (none after 6 weeks of maintenance). The risk of AE was higher in patients undergoing SCIT.ConclusionsAIT is safe and well tolerated in children and adolescents with respiratory allergies in real‐life clinical practice. Though SCIT is more prone to AE compared to SLIT, overall severe reactions are rare and occur during build‐up and early maintenance.
  • Comparative study of virulence factor genes, β-hemolysis and biofilm production in invasive and colonizing enterococci
    Milica Jovanović, Branko Velebit, Tanja Tošić, Gina Maki, Sladjana Pavić, et al.
    European Journal of Inflammation, 2023
    Objectives: In humans, enterococci are among the most important opportunistic pathogens. This study aims to compare invasive isolates obtained from blood cultures of patients with sepsis and endocarditis with colonizing isolates obtained from healthy donors’ stool samples. Methods: A case-by-case assessment was conducted on invasive infection cases to determine whether enterococci were involved in their pathogenesis. They were tested for the presence of virulence factor genes, β-hemolysis on agars supplemented with human and sheep blood, and biofilm forming capacity. Results: Three species of enterococci were identified among invasive isolates: Enterococcus faecalis, Enterococcus faecium, and Enterococcus durans. All endocarditis isolates were biofilm producers. Genes esp, gelE, asa1, ace, hyl, cylB, and cylA were present in 7 (41.2%), 11 (64.7%), 11 (64.7%), 13 (76.5%), 0, 3 (17.6%), and 1 (5.9%) invasive isolate, but none of them could be linked to a particular infection (sepsis or endocarditis). Colonizing isolates proved to have had more virulence factor genes, but the differences were not statistically significant. Members of that group produced a greater amount of biofilm when the ace gene was absent ( p = 0.047). The production of β-hemolysis by noninvasive strains was detected more frequently when agar was supplemented with human blood ( p = 0.021). In general, the presence of either cyl gene on that specific agar was in direct connection with the production of β-hemolysis: cylA ( p = 0.047) or cylB ( p = 0.020). Conclusion: We have been unable to establish any correlation between invasive isolates and any virulence gene carriage and biofilm formation. β-hemolysis was produced significantly more often by colonizing strains when agar had been supplemented with human blood.
  • Local allergic rhinitis – A big challenge in clinical practice
    Rajica Stosovic, Vesna Tomic-Spiric
    Srpski Arhiv Za Celokupno Lekarstvo, 2021
    Local allergic rhinitis is a new rhinitis phenotype characterized by symptoms similar to allergic rhinitis, in non-atopic patients with a positive nasal allergen provocation test (NAPT). The disease is diagnosed in over 25% of non-atopic patients with rhinitis, marked as non-atopic rhinitis. It most often has perennial and severe symptoms and a progressive course. It is often associated with conjunctivitis and/or asthma. It is necessary to consider local allergic rhinitis in patients with non-atopic rhinitis. The gold standard for diagnosis is a positive NAPT. Pharmacological therapy fails to stop the natural progression and development of comorbidities. Allergen immunotherapy reduces the symptoms, consumption of medicines and increases the tolerance to allergens responsible for local allergic rhinitis. New studies are needed to confirm the curative effects and evaluate the preventive effects of allergen immunotherapy.
  • Occurrence of Clostridium difficile infections in Serbia and high proportion of PCR ribotype 027 strains in two hospitals in Belgrade
    Milica Jovanović, Mitra Drakulović, Tanja Tošić, Rajica Stošović, Snežana Jovanović
    Anaerobe, 2018
  • Presence of the esp gene in Enterococcus faecium derived from oropharyngeal microbiota of haematology patients
    Milica Jovanović, Tanja Tošić, Snežana Jovanović, Rajica Stošović, Goran Stevanović, et al.
    Archives of Oral Biology, 2018
  • Study toward resolving the controversy over the definition of allergic fungal rhinosinusitis
    Aleksandra Barac, Goran Stevanovic, Marina Pekmezovic, Zoran Rakocevic, Rajica Stosovic, et al.
    Medical Mycology, 2018
    &NA; Dysbiosis of the microbiome on the airway mucosa leads to the development of chronic inflammatory and allergic disorders. The aim of this study was to consider the potential diagnostic criteria for allergic fungal rhinosinusitis (AFRS) and nonallergic fungal rhinosinusitis (FRS), and the role of fungal presence in an environment for the development of AFRS. In this study, 136 patients were divided into two groups: patients with positive specific immunoglobulin E (sIgE) and fungal finding (AFRS group), and patients with negative sIgE and positive fungal finding (FRS group). The study design included: anamnesis data, sIgE, eosinophil count and skin‐prick test, rhinology and computerized tomography (CT) observation and mycological finding. Our results showed: (i) the prevalence in Serbia is: AFRS 1.3%, FRS 2.8%; (ii) 30.4% patients with sIgE+ had more often severe and recurrent chronic rhinosinusitis (CRS) (P = .005) and the presence of polyps (P = .025); (iii) 46.4% patients with sIgE+ had positive fungi on the sinonasal mucosa and were considered as AFRS; (iv) patients with AFRS had more frequent asthma (P = .024) and chronicity of CRS >10 years (P = .000). The persistent fungal presence and prolonged duration of CRS could be a silent threat for the progression of inflammation and development of FRS. Lavage with hypertonic‐NaCl should be included in the everyday hygiene routine in an effort to decrease fungal load and antigenic exposure. The presence of allergological parameters and better response to corticosteroid therapy in AFRS patients should be considered as crucial diagnostic criteria for AFRS.
  • Local spread of Tn1546-like element among three species of vancomycin resistant enterococci in an intensive care unit
    Milica Jovanovic, Tanja Tosic, Snezana Jovanovic, Goran Stevanovic, Mitra Drakulovic, et al.
    Journal of Infection in Developing Countries, 2017
    Introduction: In an intensive care unit (ICU) of the Emergency Center in the Clinical Center of Serbia, four species of vancomycin resistant enterococci (VRE) were isolated in a 17-month period mostly from blood cultures, including E. faecalis, E. faecium, E. raffinosus and E.gallinarum.
 Methodology: The relationship between isolates from each species was investigated by PFGE, and PCR experiments for detection of pathogenicity factor genes and van genes to determine the nature of each clone. A PCR-based method, using 10 primer pairs (p1/2-p19/20), was used to investigate the presence of the Tn1546-like structure.
 Results: PFGE indicated the presence of two different E. faecium clones, while the three other enterococcal species belonged to one clone each. Transposon typing revealed that isolates of E. raffinosus (4), E. gallinarum (4) and E. faecalis (3) yielded gene sequences identical to 10 primer pairs (p1/2-p19/20), suggesting the possibility of identical transposon-like structure in these species.
 Conclusions: The results of the study indicate probable horizontal spread of Tn1546-like structure in three species of VRE obtained from the same ICU.
  • Allergic fungal sinusitis - New aspects of clinical features, laboratory diagnosis and therapy
    Valentina Arsic-Arsenijevic, Aleksandra Barac, Marina Pekmezovic, Rajica Stosovic, Ivica Pendjer
    Srpski Arhiv Za Celokupno Lekarstvo, 2013
  • Pre-asthma stage in patients with allergic rhinits
    J. Bolpacic, M. Bogic, J. Tadic, V. Tomic-Spiric, A. Peric-Popadic, et al.
    Allergologie, 2006
  • Treatment of allergic inflammations with steroidal agents
    Srpski Arhiv Za Celokupno Lekarstvo, 1999
  • The role of eosinophilic leukocytes in allergic inflammation
    Srpski Arhiv Za Celokupno Lekarstvo, 1998
  • The role of endothelial cells in allergic inflammation reactions
    Srpski Arhiv Za Celokupno Lekarstvo, 1998
  • The influence of parathyroidectomy on phagocytic capability of polymorphonuclear cells in patients on hemodialysis
    Srpski Arhiv Za Celokupno Lekarstvo, 1994
  • Importance of nonspecific and specific bronchoprokocative test in diagnosing allergic bronchial asthma
    Srpski Arhiv Za Celokupno Lekarstvo, 1994
  • Allergic reaction of the lower airways of non asthmatic patients caused by grass pollen
    Srpski Arhiv Za Celokupno Lekarstvo, 1994
  • Allergic inflamation of the lower airways in patients with allergic rhinitis
    Srpski Arhiv Za Celokupno Lekarstvo, 1994
  • Allergic reactions of the lower airways in two patients with seasonal allergic rhinitis
    Srpski Arhiv Za Celokupno Lekarstvo, 1994