Association of genetic variants of the vitamin D receptor gene with vitiligo in a tertiary care center in a Saudi population: a case-control study.

BACKGROUND: Vitiligo is a common cutaneous disorder of the skin and hair caused by a systemic depigmentation disorder that affects 1% of the population or less due to its onset in early adulthood. Meta-analyses have documented a linkage between vitiligo and the vitamin D receptor (VDR) gene. OBJECTIVE: Investigate the relationship between the ApaI, BsmI, FokI and TaqI genetic variants in the VDR gene with vitiligo in a Saudi population. DESIGN: Case-control. SETTING: Single tertiary care center. PATIENT AND METHODS: The case-control study was carried out between January 2015-December 2015 in Saudi vitiligo patients and healthy controls. VDR genetic variants or polymorphisms (ApaI, BsmI, FokI and TaqI) were genotyped by polymerase chain reaction-restriction fragment length analysis followed by 3% agarose gel electrophoresis. Applicable statistical methods were used to assess relationships between vitiligo cases and controls. MAIN OUTCOM MEASURE: Effect of genotype distribution among four single nucleotide polymorphisms. SAMPLE SIZE: 152 vitiligo (median [IQR] 23 [19] years) patients and 159 healthy controls (45 [28.5] years). RESULTS: We found an association of vitiligo with ApaI and BsmI polymorphisms (P<.05). However, a decreased risk was noted in vitiligo patients with FokI and TaqI polymorphisms and in the diplotype and haplotype analysis within males and females. A positive association with vitiligo was observed in ACAC and AC (adjusted by gender) haplotypes (P<.05). The strongest linkage disequilibrium was observed between rs79785232 (ApaI) and rs731236 (TaqI) polymorphisms (r2=.83), followed by rs2228570 (FokI) and rs1544410 (BsmI) polymorphisms (r2=.53). CONCLUSIONS: Our results confirm an association of vitiligo with ApaI and BsmI polymorphisms and fail to show an association in TaqI and FokI polymorphism with vitiligo. Additional studies need to be carried out in different Arab populations to determine whether the polymorphisms are present. LIMITATIONS: Controls not age matched, small sample size, lack of biochemical parameters. CONFLICT OF INTEREST: None.

Markers of atopic dermatitis, allergic rhinitis and bronchial asthma in pediatric patients: correlation with filaggrin, eosinophil major basic protein and immunoglobulin E.

BACKGROUND: Allergic reactions have been implicated as contributions in a number of atopic disorders, including atopic dermatitis (AD), allergic rhinitis (AR) and bronchial asthma (BA). However, the potential for filaggrin protein, eosinophil major basic protein (MBP) and immunoglobulin E (IgE) to elicit allergic response or to contribute to atopic disorders remains largely unexplored in pediatric patients. This study was undertaken to investigate the status and contribution of filaggrin protein, eosinophil MBP and total IgE in pediatric patients with AD, AR and BA. METHODS: Sera from 395 pediatric patients of AD, AR or BA with varying levels of disease activity according to the disease activity index and 410 age-matched non-atopic healthy controls were evaluated for serum levels of atopic markers, including filaggrin, eosinophil MBP and IgE. RESULTS: Serum analysis showed that filaggrin levels were remarkably high in pediatric patients with AD, followed by BA and AR, whereas its levels were low in non-atopic pediatric controls. Eosinophil MBP levels in sera of atopic patients were significantly high as compared with their respective controls, but its levels were highest in AR patients, followed by AD and BA. Total IgE in sera of AD patients was markedly high, followed by AR and BA patients, whereas its levels were low in non-atopic pediatric controls. Interestingly, not only was an increased number of subjects positive for filaggrin protein, eosinophil MBP or total IgE, but also their levels were statistically significantly higher among those atopic patients whose disease activity scores were higher as compared with atopic patients with lower disease activity scores. CONCLUSIONS: These findings strongly support a role of filaggrin protein, eosinophil MBP and IgE in the onset of allergic reactions in pediatric patients with AD, AR and BA. The data suggest that filaggrin, eosinophil MBP or IgE might be useful in evaluating the progression of AD, AR or BA and in elucidating the mechanisms involved in the pathogenesis of these pediatric disorders.

Interleukin-4 and interferon-γ are possible allergic markers in pediatric patients with ß-lactam hypersensitivity.

BACKGROUND: ß-lactam agents are known to elicit T-cell-mediated immune responses that play a central role in the onset of allergic reactions, but the involvement of specific type of cytokines in drug allergy remains largely unexplored in humans. OBJECTIVES: This study was undertaken to investigate the role of cytokines involvement in pediatric patients with ß-lactam hypersensitivity and to determine whether involvement of cytokines in drug-mediated reactions are important for the perspective of allergic patient's management. METHODS: ß-lactam-induced hypersensitivity reactions in eighty pediatric patients were determined by clinical manifestations and skin prick or intradermal testing. Production of T-helper (Th) type-1 cytokine interferon (INF)-γ, Th-2 cytokine interleukin (IL)-4, regulatory T-cell cytokine IL-10, and other cytokines IL-6 and IL-12 were determined by sandwich ELISAs. RESULTS: Diagnosis of ß-lactam allergy was confirmed in 53 pediatric patients. IL-4 secretion in patients' sera was significantly higher as compared with healthy controls (P < 0.05). However, INF-γ level in patients' sera was significantly lower as compared with controls (P < 0.05). No significant alterations were found in the protein secretion of IL-10, IL-12, and IL-6 in allergic patients as compared with controls (P > 0.05). CONCLUSION: We conclude that IL-4 is specific marker for the diagnosis of ß-lactam-induced hypersensitivity. Moreover, IL-4 in combination with INF-γ is more sensitive for the diagnosis of these reactions. This study also concludes that both IL-4 and INF-γ may play an active role in the onset of allergic reactions against ß-lactam antibiotics.

Biochemical and immunological studies on erythrocytes superoxide dismutase modified by nitric oxide in patients with alopecia areata: Implications in alopecia patchy persistent and alopecia universalis.

Alopecia areata (AA) is a non-scarring hair loss disorder that ranges in severity from patchy loss of scalp hair (AA patchy persistent; AAP) to loss of all scalp and body hair (alopecia universalis; AU). The cause of AA is unknown but most evidences support that AA has an autoimmune etiology, where free radicals play an important role. This study was undertaken to investigate the role of nitric oxide (NO) modified erythrocytes superoxide dismutase (eSOD) in AA. Data revealed that NO-induced damage in eSOD caused alteration in hydrophobic or aromatic amino acids and protein carbonyl contents. NO-specific quencher, carboxyl-PTIO further reiterates NO-modifications. Specificity of antibodies from AA patients (n=26) was analyzed toward NO-modified eSOD (NO-eSOD) and their results were compared with healthy controls (n=30). Protein-A purified IgG of AA patients (AA-IgG) showed strong binding to NO-eSOD in comparison with IgG from controls. In addition, AA-IgG from patients with AU recognized NO-eSOD in a greater extent as compared to AA-IgG from patients with AAP. Furthermore, AU patients' sera contained higher levels of NO or carbonyl contents and lower levels of SOD activity compared with AAP patients' or control sera. In conclusion, this is the first study to demonstrate the role of NO-modified-eSOD in AA. Our novel results conclude that perturbations in SOD by NO presenting unique neo-epitopes that might be one of the factors for the antigen driven antibodies induction in AA. Preferential binding of NO-eSOD by AA-IgG pointed out the likely role of NO-eSOD in the initiation/progression of AA.