Background Primary immunodeficiency disorders (PIDD) are of various types and severities, and they are associated with a delay in diagnosis. Early diagnosis of PIDD helps to improve the quality of life of affected children and prevent permanent consequences such as organ damage. Hence, awareness of PIDD is a must in the community to aid in early detection. Objectives The study aims to investigate the general population\'s awareness of PIDD in children in Arar, Northern Saudi Arabia. Methods A cross-sectional design was utilized to determine the awareness of PIDD in children in Arar, Northern Saudi Arabia. The participants were selected through an online self-administered questionnaire. The collected data was analyzed using descriptive and inferential statistics. Results A total of 528 participants were involved in the current study. The majority of the sample population falls within the 20-30 age range. 9.1% of respondents know a child with primary immunodeficiency. Additionally, participants were aware of certain symptoms, such as delayed growth and chronic diarrhea, with rates of 47.0% and 34.1%, respectively. On the other hand, symptoms like otitis media and sinusitis have lower awareness rates of 25.8% and 33.3%, respectively. Conclusion This study can help in developing targeted awareness campaigns and educational programs to improve the understanding of primary immune deficiency disease among the general population in Saudi Arabia. This, in turn, can lead to earlier diagnosis and better management of the disease in children, ultimately improving their quality of life.

The current dosing strategy of immune globulin products for the treatment of primary immunodeficiency diseases (PIDDs) in the USA is based on total body weight (BW). The aim of our study was to assess the relationship between dose and trough level, and to determine whether an alternative dosing strategy should be considered for patients who are overweight or obese. We analyzed data in a total of 533 patients from 11 studies. We modeled the relationship between trough level and dose per week using a linear mixed model. We used an over-dispersed Poisson model to model the relationship between infection and trough level. In these analyses, we then combined the study-specific treatment effects using a random-effect or fixed-effect model. The mean administered dose per week was 9.77, 14.00, or 18.17 g in patients who were normal weight, overweight, or obese, respectively. Compared with a patient of normal weight, a 1 g increase in dose per week in a patient who was overweight was associated with a smaller increase in the trough level, 0.08 g/L less (95%CI -0.14 to -0.03 g/L), and a 1 g increase in dose per week in a patient who was obese was associated with a much smaller increase in trough level, 0.01 g/L less (95% CI -0.07 to 0.06 g/L). Last, for a 1 unit (g/L) increase in trough level, the expected number of infections remained the same, with a multiplicative factor of 1.01 (95%CI 0.98-1.04). Overall, we found no compelling evidence to justify a reconsideration of the current dosing strategy based on total BW for patients with PIDDs who are overweight or obese.

PIDDosome formation followed by caspase-2 activation is critical for genotoxic stress-induced apoptotic cell death. Failure of proper caspase-2 activation causes a neurodevelopmental disorder and intellectual disability. R815W, R862W, and Q863stop mutations in p53-induced protein with a death domain (PIDD), a component of the PIDDosome, also lead to this disorder. However, the molecular mechanisms underlying this pathogenesis remain elusive. In this study, we analyzed the molecular mechanisms underlying the pathogenesis of the PIDD DD pathogenic variants R815W, R862W, and Q863stop. We determined that these mutations prevented the interaction between PIDD and RIP-associated Ich-1/Ced-3 homologous protein with a death domain (RAIDD), a molecule that mediates PIDDosome formation. The disruption of this interaction affects PIDDosome formation and caspase-2 activation.

This article aims to describe the clinical manifestations and management of COVID-19 in patients with primary and secondary B cell deficient states. We describe the epidemiologic and clinical features as well as unique management paradigm including isolation precautions with COVID-19. We then focus upon primary and secondary preventive approaches including vaccination and pre- as well as post-exposure prophylaxis. Further, we elaborate upon the important disease specific risk factors in these patients and the need to conduct prospective clinical trials to develop individualized management strategies in this population.

Pathogenic variants in LRBA, encoding the LPS Responsive Beige-Like Anchor (LRBA) protein, are responsible for recessive, early-onset hypogammaglobulinemia, severe multi-organ autoimmunity, and lymphoproliferation, with increased risk for malignancy. LRBA deficiency has a wide clinical spectrum with variable age of onset and disease severity. Three apparently unrelated patients with LRBA deficiency, of Georgian Jewish descent, were homozygous for LRBA c.6640C > T, p.R2214*, leading to a stop upstream of the LRBA BEACH domain. Despite carrying the same LRBA genotype, the three patients differed in clinical course: the first patient was asymptomatic until age 25 years; the second presented with failure to thrive at age 3 months; and the third presented at age 7 years with immune cytopenias and severe infections. Two of the patients developed malignancies: the first patient was diagnosed with recurrent Hodgkin\'s disease at age 36 years, and the second patient developed aggressive gastric cancer at age 15 years. Among Georgian Jews, the carrier frequency of the LRBA p.R2214* allele was 1.6% (4 of 236 Georgian Jewish controls). The allele was absent from other populations. Haplotype analysis showed a shared origin of the mutation. These three patients revealed a pathogenic LRBA founder allele in the Georgian Jewish population, support the diverse and complex clinical spectrum of LRBA deficiency, and support the possibility that LRBA deficiency predisposes to malignancy.

OBJECTIVE: To evaluate and describe lymphocyte populations\' and B cell subsets\' frequencies in patients presenting with Predominantly antibody deficiencies (PAD) and diagnosed with bronchiectasis or recurrent pneumonia seen in Cali (Colombian Southwest region).
METHODS: 16 subjects with PAD, 20 subjects with pulmonary complications (bronchiectasis or recurrent pneumonia) and 20 healthy donors (HD). Controls and probands between 14 and 64 years old, regardless of gender were included. Lymphocyte populations (T, B and NK cells) and B cell subsets were evaluated in peripheral blood mononuclear cells using flow cytometry, T/B/NK reagent and the pre-germinal center antibody panel proposed by the EUROflow consortium were used. EUROclass and the classification proposed by Driessen et al. were implemented.
RESULTS: CVID patients exhibited increase absolute numbers of CD8+ T cells and reduce NK cells as compare with HD, other PAD cases or pulmonary complications. PAD B cell subsets were disturbed when compared to the age range-matched healthy donors. Among B cell subsets, the memory B cell compartment was the most affected, especially switched memory B cells. Four participants were classified as B- and two CVID as smB-Trnorm and smB-21low groups according to EUROclass classification. The most frequent patterns proposed by Driessen et al. were B cell production and germinal center defect.
CONCLUSIONS: B cell subsets, especially memory B cells, are disturbed in PAD patients from Southwestern Colombia. To the best of our knowledge this is the most comprehensive study of B cell subsets in Colombian adults.

In mid-December 2020, Israel started a nationwide mass vaccination campaign against coronavirus disease 2019 (COVID-19). In the first few weeks, medical personnel, elderly citizens, and patients with chronic diseases were prioritized. As such, patients with primary and secondary immunodeficiencies were encouraged to receive the vaccine. Although the efficacy of RNA-based COVID-19 vaccines has been demonstrated in the general population, little is known about their efficacy and safety in patients with inborn errors of immunity (IEI).
Our aim was to evaluate the humoral and cellular immune response to COVID-19 vaccine in a cohort of patients with IEI.
A total of 26 adult patients were enrolled, and plasma and peripheral blood mononuclear cells were collected from them 2 weeks following the second dose of Pfizer-BioNTech COVID-19 vaccine. Humoral response was evaluated by testing anti-SARS-CoV-2 spike (S) receptor-binding domain and antinucleocapsid antibody titers and evaluating neutralizing ability by inhibition of receptor-binding domain-angiotensin-converting enzyme 2 binding. Cellular immune response was evaluated by using ELISpot, estimating IL-2 and IFN-γ secretion in response to pooled SARS-CoV-2 S- or M-peptides.
Our cohort included 18 patients with a predominantly antibody deficiency, 2 with combined immunodeficiency, 3 with immune dysregulation, and 3 with other genetically defined diagnoses. Twenty-two of them were receiving immunoglobulin replacement therapy. Of the 26 patients, 18 developed specific antibody response, and 19 showed S-peptide-specific T-cell response. None of the patients reported significant adverse events.
Vaccinating patients with IEI is safe, and most patients were able to develop vaccine-specific antibody response, S-protein-specific cellular response, or both.

Caspase-2 belongs to the caspase family of proteins responsible for essential cellular functions including apoptosis and inflammation. Uniquely, caspase-2 has been identified as a tumor suppressor, but how it regulates this function is still unknown. For many years, caspase-2 has been considered an \"orphan\" caspase because, although it is able to induce apoptosis, there is an abundance of conflicting evidence that questions its necessity for apoptosis. Recent evidence supports that caspase-2 has non-apoptotic functions in the cell cycle and protection from genomic instability. It is unclear how caspase-2 regulates these opposing functions, which has made the mechanism of tumor suppression by caspase-2 difficult to determine. As a protease, caspase-2 likely exerts its functions by proteolytic cleavage of cellular substrates. This review highlights the known substrates of caspase-2 with a special focus on their functional relevance to caspase-2\'s role as a tumor suppressor.

Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder caused by defects in the NADPH oxidase complex. Mutations in NCF2 encoding the cytosolic factor p67phox result in autosomal recessive CGD. We describe three patients with a novel c.855G>C NCF2 mutation presenting with diverse clinical phenotype. Two siblings were heterozygous for the novel mutation and for a previously described exon 8-9 duplication, while a third unrelated patient was homozygous for the novel mutation. Mutation pathogenicity was confirmed by abnormal DHR123 assay and absent p67phox production and by sequencing of cDNA which showed abnormal RNA splicing. Clinically, the homozygous patient presented with suspected early onset interstitial lung disease and NCF2 mutation was found on genetic testing performed in search for surfactant-related defects. The two siblings also had variable presentation with one having history of severe pneumonia, lymphadenitis, and recurrent skin abscesses and the other presenting in his 30s with discoid lupus erythematosus and without significant infectious history. We therefore identified a novel pathogenic NCF2 mutation causing diverse and unusual clinical phenotype.

In this era of cutting edge research, though one of the ubiquitous facilities accessible to modern man is state of the art medical care yet diabetes has emerged as one of the major ailments afflicting the present generation. So the prime necessity of this age has transformed into providing cheap and sustainable medical care against such major diseases like diabetes. In layman\'s terms Diabetes may be defined as a physiological condition wherein the blood glucose level is more than the prescribed level on a regular basis.
So the prime objective of this work is to provide a novel classification technique for detection of diabetes in a timely and effective manner.
The proposed work comprises of four phases: In the first phase a \"Localized Diabetes Dataset\" has been compiled and collected from Bombay Medical Hall, Mahabir Chowk, Pyada Toli, Upper Bazar, Jharkhand, Ranchi, India. In the second phase various classification techniques namely RBF NN, MLP NN, NBs, and J48graft DT have been applied on the Localized Diabetes Dataset. In the third phase, Genetic algorithm (GA) has been utilized as an attribute selection technique through which six attributes among twelve attributes have been filtered. Lastly in the fourth phase RBF NN, MLP NN, NBs and J48graft DT has been utilized for classification on relevant attributes obtained by GA.
In this study, comparative analysis of outcomes obtained by with and without the use of GA for the same set of classification technique has been done w.r.t performance assessment. It has been conclusively inferred that GA is helpful in removing insignificant attributes, reducing the cost and computation time while enhancing ROC and accuracy.
The utilized strategy may likewise be executed for other medical issues.