Adverse reactions in venom immunotherapy protocols: conventional versus ultra-rush.

BACKGROUND: Venom immunotherapy (VIT) is an effective treatment in the patients at high risk of anaphylaxis or life-threatening systemic reactions due to Hymenoptera venom allergy. But, systemic and large local reactions can be observed, especially during the build-up phase of VIT. We evaluated the safety of conventional and ultra-rush build-up protocols. MATERIALS AND METHODS: Two protocols in 71 patients (39 conventional and 32 ultra-rush protocols) with honeybee and wasp venom allergy were evaluated retrospectively. Patients were diagnosed and selected for VIT according to the criteria established by the European Academy of Allergy and Clinical Immunology. The severity of systemic reactions was evaluated according to the criteria of Mueller. RESULTS: Build-up phases were tolerated in 66.2% (n = 47) without any reaction. Allergic adverse reactions were observed in 33.8% (n = 24): large local reactions 22.5% (n = 16) and systemic reactions 11.3% (n = 8). There was no significant difference in the number of adverse reactions comparing patients receiving conventional and ultra-rush protocol. In addition, no association was found between allergic adverse reactions and the following factors: sex, previous systemic sting reactions, honeybee and wasp venom extract. CONCLUSION: We found that both protocols were tolerated in patients with honeybee and wasp venom allergy. Ultra-rush protocol will be preferred for patients and clinicians because of its advantages in terms of time and costs.KEY MESSAGESVIT is the only curative treatment method that reduces the risk of severe reactions after a bee sting and improves the quality of life in patients with Hymenoptera venom allergy.Ultra-rush VIT protocol has advantages such as few injection and time savings.Both ultra-rush and conventional VIT are safe treatments to prevent potentially life-threatening reactions in patients with honeybee and wasp venom allergy.

Efficacy of sodium hyaluronate in relieving nasal symptoms of children with intermittent allergic rhinitis: a randomized controlled trial.

PURPOSE: Nasal irrigation is recommended as add-on therapy in patients with intermittent allergic rhinitis (AR). We aimed to evaluate the clinical efficacy of adding hyaluronic acid (HA) or normal saline solution (NSS) to nasal corticosteroid (NC) therapy as add-on therapy in improving quality of life and reducing nasal symptom scores of children with intermittent AR compared to NC therapy. METHOD: In this 28-day long, open-label, randomized controlled trial, one puff of NC was administered once a day through both nostrils of 76 children with SAR (6-12 years old), whose Total Nasal Symptom Score (TNSS) was ≥ 4. Twenty-six patients received NC only (Group 1); 24 patients received NSS (Group 2), and 26 patients received HA (Group 3) twice a day by means of nasal douche device. Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) and TNSS were measured as subjective parameters, and nasal eosinophil count (NEC) in nasal cytology, nasal airflow (NAF), and resistance were measured as objective parameters. RESULTS: No significant difference was found in post-treatment between groups in terms of TNSS, PRQLQ, and NEC values. Mean values of post-treatment left NAF of the groups were significantly different (p = 0.030), and the mean value of Group 3 was the highest (mean ± SD = 247.62 ± 155.8 ccm/sn). In comparing pre- and post-treatment intragroup mean total NAR (TNAR) values, a statistically significant decrease was recorded only in group three (p = 0.025). CONCLUSION: The addition of HA to NC as an adjunct therapy in children with intermittent AR has limited beneficial effects in our study and deserves further investigation. TRIAL REGISTRY: The clinical trial registration number ID:NCT04752956.

Phenotypically defined subpopulations of circulating follicular helper T cells in common variable immunodeficiency.

BACKGROUND: Common variable immunodeficiency (CVID) is characterized by low immunoglobulin G and IgA/IgM, decreased switched memory B cells, impaired response to vaccine, and an increased susceptibility to infections and autoimmunity. TFH cells play an important role in germinal center reaction where it supports isotype switching, somatic hypermutation, generation of memory B cells, and differentiation of B cells to plasma cells. The objective was to study the distribution of three subsets of TFH cells and their relationship with autoimmune diseases associated with CVID. METHODS: TFH cells have been divided into TFH 1 (interleukin 21 [IL-21] and interferon γ), TFH 2 (IL-21 and IL-4), and TFH 17 (IL-21 and IL-17) cells. Mononuclear cells from 25 patients with CVID and age and gender-matched controls were stained with various monoclonal antibodies (anti-CD4 APC, anti-CXCR5 FITC, anti-CCR6 PerCP, and anti-CXCR3 PE) and isotype controls and analyzed for TFH 1 (CD4+ CXCR5+ CXCR3+ CCR6- ), TFH 2 (CD4+ CXCR5+ CXCR3- CCR6- ), and TFH 17 (CD4+ CXCR5+ CXCR3- CCR6+ ) cells by multicolor flow cytometry. Twenty thousand cells were acquired and analyzed by FlowJo software. Statistical analysis of comparison of patients and healthy controls was performed by paired t test using PRISM 7 software. RESULTS: TFH 2 and TFH 17 cells subpopulations of TFH cells were significantly decreased (P < .003 and P < .006, respectively) in CVID as compared with controls. No significant difference was observed in any of TFH cell subpopulations between CVID with and those without autoimmunity group. CONCLUSION: Alterations in TFH cell subpopulation may play a role in defects in B cell compartment in CVID.

Haplotype analysis in a 16-year-old boy with vancomycin-induced DRESS syndrome.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare but life-threatening multisystem adverse reaction to a medication, with vancomycin being one of the most common cause reported. We present the HLA analysis of a pediatric patient who developed DRESS related to vancomycin and compared the results with the available literature. With further data, the use of pretreatment HLA analysis to prevent vancomycin related DRESS may be a valuable option in the near future.

Phenotypic Analysis of CD4+ Treg, CD8+ Treg, and Breg Cells in Adult Common Variable Immunodeficiency Patients.

INTRODUCTION: Regulatory lymphocytes (CD4+ T regulatory cells [Treg], CD8+ Treg, and B regulatory cells [Breg]) play a critical role in immune homeostasis and tolerance. Common variable immunodeficiency (CVID) is associated with increased susceptibility to infections and increased frequency of inflammatory and autoimmune diseases. CD4+ Treg cell abnormalities have been reported in CVID; however, CD8+ Treg cells have not been reported in CVID. The objective of this study was to evaluate CD4+ Treg and CD8+ Treg cells in CVID patients. METHODS: In 25 patients with CVID and age-matched healthy controls, Treg cells, evaluated in freshly isolated peripheral blood mononuclear cells (natural; nCD4+ Treg and nCD8+ Treg) and following in vitro activation with anti-CD3/CD28 monoclonal antibodies (induced; iCD4+ Treg and iCD8+ Treg) as well as Breg cells were analyzed with specific monoclonal antibodies and isotype controls using flow cytometry. RESULTS: The proportions of nCD4+ Treg (CD4+ CD127low CD25high FoxP3+), iCD4+ Treg (CD4+ CD127low CD25high FoxP3+), iCD8+ Treg (CD8+ CD25high CD183+ FoxP3+), and Breg (CD19+ CD24high CD38high) lymphocytes were significantly lower in patients with CVID than in controls. CONCLUSIONS: Altered regulatory lymphocytes may play a role in the pathogenesis and autoimmunity and inflammation associated with CVID.

Evaluation of chemerin and its receptors, ChemR23 and CCRL2, in gingival tissues with healthy and periodontitis.

Chemerin is a chemoattractant protein that directs inflammatory cells that express its receptor chemokine receptor-like 1 (ChemR23) towards sites of inflammation. C-C chemokine receptor-like 2 (CCRL2), is the other receptor of chemerin, improves the interaction between chemerin and ChemR23. The aim of this study was to evaluate the expression of chemerin and its receptors in gingival tissues with healthy and periodontitis. Tissue biopsy samples were obtained from 20 patients with chronic periodontitis and from the gingiva of 20 healthy individuals undergoing a crown lengthening process. Quantitative real-time PCR (qPCR) was used to examine the mRNA expression of chemerin, ChemR23 and CCRL2. Additionally, protein expression was measured by immunohistochemistry. Both qPCR and immunohistochemistry results revealed that the expression of chemerin and ChemR23 was significantly higher in tissues with periodontitis than in healthy tissues (P = 0.001 and, P = 0.015, respectively). There were no significant differences between healthy tissues and those with periodontitis in terms of mRNA expression of CCRL2, whereas a more intense staining was observed in tissues with periodontitis. The mRNA expression levels of chemerin showed a positive correlation with plaque index, gingival index, probing pocket depth and clinical attachment level (r = 0.448, r = 0.460, r = 0.439 and, r = 0.459, respectively, P < 0.01). To the best of our knowledge, this study is the first to examine the expression of chemerin, ChemR23 and CCRL2 in gingival tissues. Our study suggests that chemerin may play a role in the pathogenesis of periodontitis by causing chemoattraction of immune cells that direct ChemR23 receptors to the site of inflammation.

Adults with common variable immunodeficiency: a single-center experience.

BACKGROUND/AIM: In this study, we aimed to assess the clinical and immunological findings of our patients with common variable immunodeficiency (CVID). MATERIALS AND METHODS: We analyzed the records of 31 adult patients with CVID (12 females, 19 males). The patients were classified into clinical and immunophenotypic subgroups for statistical comparisons. RESULTS: Our patients had some clinical signs in considerable frequencies, such as low body weight (45.2%), urinary tract infections (41.9%), various dermatoses (35.5%), and oral aphthae (32.3%). The histological findings in the biopsy specimens of the gastrointestinal tract (nodular lymphoid hyperplasia, villous atrophy, and lymphocytic infiltrates at mucosa) were significantly associated with splenomegaly, hepatomegaly, or low body weight (P = 0.005, 0.045, and 0.007, respectively). The patients with low CD4/CD8 ratios had lower IgG levels and a lower percentage of CD19+ B cells, but a higher percentage of activated T cells (P = 0.023, 0.011, and 0.028, respectively). CONCLUSION: In adults with CVID, there existed some clinical signs at considerable frequencies, but these are not overemphasized in the literature. The CD4/CD8 ratio is an important factor in antibody production and the clinical presentation of CVID. It seems that the adaptive immune system is on alert and subclinical immune activation insidiously continues in patients with CVID.

Increased visfatin expression is associated with nuclear factor-kappa B and phosphatidylinositol 3-kinase in periodontal inflammation.

OBJECTIVE: Visfatin is an adipocytokine that plays a role in regulating periodontal inflammation by as yet identified mechanisms. It has been suggested that visfatin mediates inflammation via activation of the nuclear factor-kappa B (NF-κB) and phosphatidylinositol 3-kinase (PI3k) signaling pathways which play a role in the inhibition of neutrophil apoptosis. The aim of this study was to investigate the expression of visfatin, NF-κB (NF-κB1 and NF-κB2), PI3k, tumor necrosis factor alpha (TNF-α), and interleukin-1 beta (IL-1ß) in the tissue of healthy individuals and patients with periodontitis. MATERIALS AND METHODS: Tissue biopsy samples were obtained from 21 patients with chronic periodontitis and from the gingiva of 19 healthy individuals undergoing crown lengthening. The mRNA expression levels of visfatin, NF-κB, PI3k, TNF-α, and IL-1ß were evaluated by quantitative real-time PCR (qPCR). Also, visfatin protein expression was measured by immunohistochemistry. RESULTS: Both qPCR and immunohistochemistry results revealed that the visfatin expression was higher in the tissues with periodontitis than in healthy tissues (P < 0.01). Similarly, the mRNA expression levels of NF-κB2, PI3k, and IL-1ß were higher in tissues with periodontitis than in healthy gingival tissues (P < 0.01). Visfatin was positively correlated with the levels of NF-κB1 (r = 0.549, P < 0.05), NF-κB2 (r = 0.636, P < 0.05), PI3k (r = 0.682, P < 0.01), TNF-α (r = 0.558, P < 0.05), and IL-1ß (r = 0.686, P < 0.01) in the tissues with periodontitis. CONCLUSIONS: Our results demonstrated that increased visfatin was associated with the expression of NF-κB and PI3k which may play a role in the pathogenesis of periodontitis. We suggest that increased visfatin may contribute to the inhibition of neutrophil apoptosis via the NF-κB and PI3k signaling pathways. CLINICAL RELEVANCE: Understanding the role of visfatin in periodontitis will enable the development of new treatment methods for inflammation.

Killer-cell immunoglobulin-like receptor and human leukocyte antigen-C genes in common variable immunodeficiency.

BACKGROUND: We aimed herein to investigate the killer-cell immunoglobulin-like receptor (KIR) genes and human leukocyte antigen (HLA)-C alleles in patients with common variable immunodeficiency (CVID), and to reveal their differences from those in healthy population. METHODS: In all, 18 patients who have been diagnosed with CVID and 15 living donors of kidney transplant recipients were enrolled in the study. Polymerase chain reaction-sequence-specific primer (PCR-SSP) typing method was used in molecular genetic analysis. The frequencies of the genes in the study groups were statistically compared with each other using chi-square or Fisher exact tests, whichever were appropriate. RESULTS: Although there was no significant difference between both study groups with respect to distribution of KIR and HLA-C2 group genes, HLA-Cw7 allele frequency in patients with CVID was significantly lower than that in healthy population (P = 0.008). CONCLUSION: This present study results support that HLA-Cw7 allele, an inhibitor of KIR ligand, may play a role in the pathogenesis of CVID.

Desensitization to Adalimumab: An Example of Repeated Desensitization to a Biological Agent.

Biological agents seem to have been more effective than classic immunosuppressive drugs; however, the adverse events including the hypersensitivity reactions are the main drawbacks of these drugs. We report a 35-year-old man who was treated with adalimumab for ankylosing spondylitis, had a local reaction on the injection site, and generalized itching with rash at the 62nd dose and repeated desensitizations to him with adalimumab. One month after the reaction, skin prick test was performed with a commercial preparation of adalimumab. The skin prick test result was determined positive comparing to positive and negative controls. Because of insufficient responses to other drugs, adalimumab desensitization was performed and the whole process was completed without any reaction. Six months later the patient gave up therapy because of a new reaction which was caused by a possible viral infection. Desensitization was repeated successfully 3 months later. Because there are few cases in the literature about adalimumab desensitization process, there is no standard desensitization protocol for the adalimumab allergy yet. Therefore, we suggest that our case report may contribute to the formation of a standardized desensitization protocol in adalimumab hypersensitivity.

Ruptured sinus of Valsalva aneurysm associated with noncompaction of the ventricular myocardium.

Rupture of a sinus of Valsalva aneurysm is a rare, but life-threatening cardiac abnormality that requires surgical correction when diagnosed, and is frequently associated with other congenital defects, particularly with ventricular septal defect, aortic valve regurgitation, and bicuspid aortic valve. We present the case of a 21-year-old man who had a ruptured aneurysm of the noncoronary sinus into the right atrium, a ventricular septal defect, a persistent left superior vena cava and a noncompaction of the ventricular myocardium diagnosed by two-dimensional echocardiography. Surgical repair was carried out and the patient made an uneventful recovery.