Association Between IL16 Gene Polymorphism and Allergic Contact Dermatitis Among Construction Workers

Objectives: First, this research was instituted to identify common allergens, and second, to test the association between IL16 gene promoter polymorphism rs4778889 T/C and allergic contact dermatitis (ACD). Methods: A case control study was conducted in dermatology outpatients’ clinic. Study subjects received interview-based semi-structured questionnaire, complete skin examination, IL16 gene promoter was investigated by PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) analysis, and IQ Ultra™ patch test units (Chemotechnique Diagnostics AB, Sweden) with 10 substances were used. Results: Most of the prevalent cases had positive patch test (93.3%). The most common clinical presentation of ACD in our patients was itching (96.7%), followed by dryness (86.75%), erythema (76.7%), and fissuring (76.7%). There was higher CC gene distribution among cases, but there was no statistically significant difference. IL16 gene distribution was nearly similar among different clinical presentations. Formaldehyde showed statistically significant higher frequency for CC. The most common allergen found was mercury chloride (76.6%), followed by potassium dichromate (26.6%) and cobalt chloride (20%). Conclusions: The current study found prominent metal sensitization (mercury chloride) over the previously known potassium dichromate. There was no statistically significant IL16 gene distribution among cases compared with control. However, C allele was more frequently encountered in cases. Further studies are required to test the association with IL16 genotype and ACD and highlight the new trends in metal sensitization among cement-exposed workers.

Acute Hereditary Angioedema With Airway Compromise: Avoiding Airway Intervention With C1 Inhibitor Concentrate

Introduction: Hereditary angioedema (HAE) is an autosomal dominant disease caused by deficiency of the plasma protein C1 inhibitor (C1-INH). Patients classically present with recurrent localized subcutaneous or submucosal edema lasting for 2 to 5 days, severe abdominal pain, or acute airway obstruction which can be fatal. Case presentations: We highlight 2 patients with acute airway compromise secondary to HAE who were successfully treated with plasma-derived C1-INH concentrates. Conclusions: The timely administration of plasma-derived C1-INH concentrates for the acute treatment of HAE has been proven to be effective in both patients in aborting an airway complication. A high index of suspicion is required for the early diagnosis and treatment of this potentially fatal condition.

Involvement of Immune Regulation in Multiple Sclerosis

Multiple sclerosis (MS) is a neurodegenerative disease characterized by neuroinflammation and demyelination that results in axon loss. Multiple sclerosis has been shown to be the result of an autoimmune response caused by a mixture of genetic and environmental factors. Dendritic cells are prominent antigen-presenting cells that interact with various molecules to regulate the immune system. The dysfunction of various features of immune regulation, including interleukins (ILs), CD4+ T cells, and suppressor of cytokine signaling (SOCS1), has been implicated in the pathogenesis of MS. T cells, particularly through the malfunction of B7-costimulatory pathways, have been shown to affect the progression of the disease. SOCS1 is important in regulating the function of T cells through its interactions with other nearby genes, especially CLEC16A, with abnormal decreases in SOCS1 expression leading to the exhibition of MS symptoms. The activation of IL-23 receptors on CD4+ T cells is pivotal to their differentiation into pathogenic TH17 cells. Several promising compounds that downregulate gene expression of IL-23 and IL-23R have been discovered but require further investigation for efficacy and safety. Given their role in the severity and progression of MS, therapies that decrease these dysregulations may ultimately decrease symptoms and in turn improve patients’ quality of life.

Immunity against Fungal Infections

Fungal diseases are major causes of morbidity and mortality among the immunocompromised, including HIV-infected individuals and patients with cancer. Individuals without a weakened immune system can also suffer from these infections. Not surprisingly, fungi are a major target for the immune system, rendered visible to it by expression of pathogen-associated molecular patterns/signatures. We now appreciate the roles of both innate and adaptive immunity in eliminating fungal infections, and how a disproportionate or inadequate immune response can diminish the host's capacity to eliminate fungi. This review focuses on our current understanding of the roles of innate and adaptive immunity in clearing common and emergent fungal pathogens. A clearer understanding of how the host's immune response tackles fungal infection may provide useful clues as to how we might develop new agents to treat those diseases in the future.

Characterization of Plasmodium falciparum Proteome at Asexual Blood Stages for Screening of Effective Vaccine Candidates: An Immunoinformatics Approach

Malaria is a complex parasitic disease that is currently causing great concerns globally owing to the resistance to antimalarial drugs and lack of an effective vaccine. The present study involves the characterization of extracellular secretory proteins as vaccine candidates derived from proteome analysis of Plasmodium falciparum at asexual blood stages of malaria. Among the screened 32 proteins, 31 were predicted as antigens by the VaxiJen program, and 26 proteins had less than two transmembrane spanning regions predicted using the THMMM program. Moreover, 10 and 5 proteins were predicted to contain secretory signals by SignalP and TargetP, respectively. T-cell epitope prediction using MULTIPRED2 and NetCTL programs revealed that most of the predicted antigens are immunogenic and contain more than 10% supertype and 5% promiscuous epitopes of HLA-A, -B, or -DR. We anticipate that T-cell immune responses against asexual blood stages of Plasmodium are dispersed on a relatively large number of parasite antigens. This is the first report, to the best of our knowledge, offering new insights, at the proteome level, for the putative screening of effective vaccine candidates against the malaria pathogen. The findings also suggest new ways forward for the modern omics-guided vaccine target discovery using reverse vaccinology.

Examination of Single Nucleotide Polymorphisms in Acetylcholine Receptors in Chronic Fatigue Syndrome Patients

Objective Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a disorder characterized by debilitating fatigue accompanied by pain and impairments in memory, cognition, and concentration. Acetylcholine (ACh) has a plethora of roles in neuronal and neuromuscular transmission. There are two types of ACh receptors, muscarinic and nicotinic, comprising 17 different subunits of the nicotinic ACh receptor (nAChR) and five different subtypes of the muscarinic receptor (mAChR) that have been identified in humans. The purpose of this study was to determine the role of ACh receptor (nAChRs and mAChRs) single nucleotide polymorphisms (SNPs) in CFS/ME patients. Methods One-hundred and fifteen CFS/ME patients (age = 48.68 ± 1.06 years) and 90 nonfatigued controls (age = 46.48 ± 1.22 years) participated in this study, where CFS/ME patients were defined according to the 1994 Center for Disease Prevention and Control (CDC) criteria. A total of 464 SNPs for nine mammalian ACh receptor genes ( M1, M2, M3, M4, M5, alpha 2, 5, 7, and 10) were examined via the Agena Biosciences iPLEX Gold assay. Statistical analysis was performed using the PLINK analysis software. Results Seventeen SNPs were significantly associated with CFS/ME patients compared with the controls. Nine of these SNPs were associated with mAChRM3 (rs4463655; P = 0.00281, rs589962; P = 0.00348, rs1072320; P = 0.00371, rs7543259; P = 0.00513, rs6661621; P = 0.00536 rs7520974; P = 0.0167, rs726169; P = 0.02349, rsrs6669810; P = 0.02361, rsrs6429157; P = 0.0375), while the remainder were associated with nAChR alpha 10 (rs2672211; P = 0.0107, rs2672214; P = 0.0108, rs2741868; P = 0.01185, rs2741870; P = 0.01281, rs2741862; P = 0.03043), alpha 5 (rs951266; P = 0.01153; rs7180002, P = 0.03682), and alpha 2 (rs2565048; P = 0.01403). Conclusion The data from this pilot study suggest an association between ACh receptors, predominantly M3 and CFS. ACh receptor SNPs may contribute to the pathomechanism of CFS/ME.

Examination of Single Nucleotide Polymorphisms (SNPs) in Transient Receptor Potential (TRP) Ion Channels in Chronic Fatigue Syndrome Patients

Background The transient receptor potential (TRP) superfamily in humans comprises 27 cation channels with permeability to monovalent and divalent cations. These channels are widely expressed within humans on cells and tissues and have significant sensory and regulatory roles on most physiological functions. Chronic fatigue syndrome (CFS) is an unexplained disorder with multiple physiological impairments. OBJECTIVES The purpose of this study was to determine the role of TRPs in CFS. Methods The study comprised 115 CFS patients (age = 48.68 ± 1.06 years) and 90 nonfatigued controls (age = 46.48 ± 1.22 years). CFS patients were defined according to the 1994 Center for Disease Prevention and Control criteria for CFS. A total of 240 single nucleotide polymorphisms (SNPs) for 21 mammalian TRP ion channel genes ( TRPA1, TRPC1, TRPC2, TRPC3, TRPC4, TRPC6, TRPC7, TRPM1, TRPM2, TRPM3, TRPM4, TRPM5, TRPM6, TRPM7, TRPM8, TRPV1, TRPV2, TRPV3, TRPV4, TRPV5, and TRPV6) were examined via the Agena Biosciences iPLEX Gold assay. Statistical analysis was performed using the PLINK analysis software. Results Thirteen SNPs were significantly associated with CFS patients compared with the controls. Nine of these SNPs were associated with TRPM3 (rs12682832; P < 0.003, rs11142508; P < 0.004, rs1160742; P < 0.08, rs4454352; P < 0.013, rs1328153; P < 0.013, rs3763619; P < 0.014, rs7865858; P ≤ 0.021, rs1504401; P ≤ 0041, rs10115622; P ≤ 0.050), while the remainder were associated with TRPA1 (rs2383844; P ≤ 0.040, rs4738202; P ≤ 0.018) and TRPC4 (rs6650469; P ≤ 0.016, rs655207; P ≤ 0.018). Conclusion The data from this pilot study suggest an association between TRP ion channels, predominantly TRPM3 and CFS. This and other TRPs identified may contribute to the etiology and pathomechanism of CFS.

HLA-A, -B, -C, -DRB1, and -DQB1 Allele Lineages and Haplotype Frequencies among Saudis

There are few reported studies on Saudi population for human leukocyte antigens (HLA) genes. We investigated allele lineages (two-digit) and haplotype frequencies of HLA-A, -B, -C, -DRB1, and -DQB1 loci in 499 healthy unrelated individuals, selected from potential bone marrow transplant (BMT) families’ donors at King Fahad Medical City (KFMC), Saudi Arabia (SA). Genotyping was performed by Sequence Specific Oligonucleotide Probe (SSOP) utilizing a Luminex-based method. Allele lineages and haplotype frequencies were evaluated along with principal component analysis (PCA) to compare findings with previously reported data on Arab related populations. A total of 18 allele lineages for HLA-A, 28 for -B, 14 for -C, 13 for -DRB1, and 5 for -DQB1 were detected. High values for linkage disequilibrium indicators were found for B:C ( D’ = 0.86599) and DRB1:DQB1 ( D’ = 0.89468) loci. Additionally, PCA results confirmed previous findings on this population, but also indicated some genetic distances from other Arab related populations. The present study helps in further investigations of this population in anthropological analysis and HLA-associated disease studies.