Uniparental Disomy of Chromosome 4: A Case of Whole Chromosome UPD Presenting with LRBA Deficiency.

PURPOSE: Lipopolysaccharide-responsive beige-like anchor protein (LRBA) encodes a widely expressed cytosolic protein that participates in polarized vesicle trafficking. Homozygous loss-of-function LRBA mutations can lead to immune deficiency due to the lack of immune regulation, classified as a part of Tregopathies. We present a case of a 49-year-old female, with polyarthralgia in metacarpophalangeal and proximal interphalangeal joints bilaterally, and morning stiffness, leading to the diagnosis of rheumatoid arthritis treated with pulse steroid therapy. She had experienced sepsis and in-depth scrutiny revealed panhypogammaglobulinemia. After being referred to the immunology clinic, she was followed under the diagnosis of common variable immunodeficiency (CVID)-like inborn errors of immunity (IEI). METHODS AND RESULTS: Physical examination and diagnostic follow-up revealed massive splenomegaly accompanied by portal hypertension, and ulcerations in the colon. She also presented with periodic hematuria and dysuria. Cystoscopic biopsy revealed mast cell-derived interstitial cystitis which has not been previously reported in LRBA deficiency in the literature to our knowledge. A multi-gene next-generation sequencing panel performed for immune deficiencies (264 genes and 524 amplicons), resulted in the identification of an apparently homozygous LRBA mutation (p.Arg722His) in the Beige and Chediak-Higashi (BEACH) domain. The SNP array showed copy neutral absence of heterozygosity of the entire chromosome 4, which is consistent with uniparental isodisomy of chromosome 4. CONCLUSION: In conclusion, this case study underscores the critical role of LRBA in immune regulation and highlights the clinical heterogeneity associated with LRBA deficiency. The patient's presentation with severe immune dysregulation, including massive splenomegaly, portal hypertension, and the novel finding of mast cell-derived interstitial cystitis, expands the clinical spectrum of LRBA mutations. The identification of an apparently homozygous LRBA mutation via next-generation sequencing further emphasizes the importance of genetic analysis in diagnosing monogenic defects manifested as CVID-like phenotype. This is the first reported case of LRBA deficiency due to whole chromosome UPD to our knowledge. Future research should focus on elucidating the full range of clinical manifestations and developing targeted therapies for patients with LRBA deficiency.

The perspective of allergy and immunology specialists on the innovations of metaverse: A survey study.

BACKGROUND: New technologies have resulted in dramatic shifts in the field of medicine, and it stands to reason that metaverse will also affect the practice of allergy and immunology. This study aimed to determine the attitudes of allergists and raise awareness about metaverse applications in allergy and immunology. METHODS: A nationwide survey-based study was conducted in Turkey. First, a 28-item questionnaire was developed and sent to Turkish allergists. After completing the first questionnaire, the participants were asked to watch a 5-min informative video about the metaverse. Lastly, a second survey was conducted to evaluate the changes in the views of the participants. RESULTS: A total of 148 allergy doctors in Turkey participated in the survey. After watching a video containing updated information about the metaverse, there was a significant increase in the importance that participants attributed to the use of virtual reality and augmented reality applications in the field of immunology and allergy (P < 0.05). Additionally, there was a significant increase in the percentage of participants who thought that Metaverse applications could be integrated into the existing system and said that this possibility excited them (P < 0.05). There was also a significant increase in the percentage of participants who thought this innovative technology could be helpful in patient examination, student and physician education, allergy testing, and patient education (P < 0.05). CONCLUSIONS: Our results demonstrate that providing information to professionals working in the field can positively influence physicians' views on the potential of the metaverse, which is a valuable tool in the field of immunology and allergy.

Successful Rapid Drug Desensitization with A Modified Protocol To Alemtuzumab in A Multiple Sclerosis Patient with Severe Immediate-Type Hypersensitivity Reaction.

Alemtuzumab is a humanized monoclonal antibody targeting the CD52 antigen on lymphocyte surfaces. The intravenous administration of alemtuzumab provokes the depletion of lymphocytes by antibody-dependent and complement-mediated cellular cytotoxicity. Resulting cytotoxicity leads to 'first-dose infusion-related reactions in more than 90% of the patients, fewer than 3% being severe cases. We present the first successful modified rapid drug desensitization (RDD) protocol to alemtuzumab in an active relapsing-remitting multiple sclerosis (RRMS) patient. The forty-year-old female patient had an immunologically-mediated mixed-type (co-occurring IgE-mediated and cytokine release syndromes) hypersensitivity reaction (HSR) verified with a drug skin test. As the patient had severe HSR and there was no other option to treat RRMS at that time; two courses of 12 mg alemtuzumab with one-year intervals were administrated successfully using the modified 12-step intravenous RDD protocol. By experience, RDD is known as a safe and effective therapy option allowing alemtuzumab treatment targeted for the aforementioned type of MS.

CoronaVac/Sinovac COVID-19 Vaccine-Related Hypersensitivity Reactions and Second-Dose Vaccine Administration: Tertiary Allergy Center Experience.

INTRODUCTION: The COVID-19 pandemic has caused a global health crisis. To prevent the disease, the Ministry of Health of Turkey gained approval for the CoronaVac COVID-19 vaccine for emergency use as the first-line. This study aimed to evaluate patients who developed hypersensitivity reactions (HRs) due to the CoronoVac vaccine and to share our experience of administering the second dose of vaccine to these patients. METHODS: The study group included the patients who presented to the Ege University Allergy and Immunology Division between January and May 2021. Demographic data, atopic status, allergic reactions to the first dose of the COVID-19 vaccine and the route of second-dose vaccine administrations were recorded. RESULTS: A total of 7 patients (four healthcare professionals), 6 (86%) of whom were women, with an average age of 53.4 years, were included in the study. The rate of allergic reactions among Ege University health workers was 0.036% (2/5,558). Six of our patients had a history of additional allergic diseases and comorbid diseases. None had any allergic reactions to previous vaccinations and latex allergy. Reactions developed commonly on the skin, as generalized urticaria/angioedema and pruritus. The severity of the reactions was evaluated as mild in 2, moderate in 3, and severe in 2 cases. The second-dose CoronaVac was safely administered by using a gradually increase dose in a total of 6 patients. CONCLUSION: In patients with HRs due to Sinovac in the first dose, the second dose can be safely performed using a gradually increased dose.

Investigating the Role of JAK/STAT Pathway on Dasatinib-Induced Apoptosis for CML Cell Model K562.

We aimed to evaluate the cytotoxic and apoptotic effects of dasatinib (BMS-354825) on K562 chronic myeloid leukemia (CML) cells and to examine the roles of STAT genes on dasatinib-induced apoptosis. The results showed that dasatinib decreased proliferation and induced apoptosis in K562 cells in a dose- and time-dependent manner. mRNA and protein levels of STAT5A and STAT5B genes were significantly reduced in dasatinib-treated K562 cells. These data indicated that STAT inhibition by dasatinib might be therapeutic in JAK/STAT pathway-associated malignancies after confirmation with clinical studies.