MicroRNA-183-5p regulates MITF expression in vitiligo skin depigmentation.

Microphthalmia-associated transcription factor (MITF) is a master regulatory factor for melanocytes. MITF regulates multiple pigmentary genes for maintaining cellular homeostasis. MicroRNAs (miRNAs) play crucial roles in numerous biological processes however their molecular/cellular mechanisms to regulate pigmentation have not been fully explored. This study was undertaken to investigate the role of miRNAs in skin depigmentation via regulation of MITF gene. Depigmentation in C57BL/6 black mice was induced by an autoimmune response against tyrosinase. Bioinformatics approach was used to detect miRNAs conserved in 3'untraslated region (3'UTR) of MITF mRNA. The iMC23 mouse melanocytes were used for transfection experiments. The data demonstrated that the MITF mRNA/protein was markedly low in lesional skin of depigmented mice (p < 0.05). Targetscan genomic database determined that 3'UTR of mouse MITF constitutes 4819 nucleotide bases and has 23 conserved sites for different miRNAs To validate the pairing of these predicted miRNAs with MITF mRNA, five miRNAs were deregulated in lesional skin (p < 0.05). Among them, mmu-miR-181a-5p and mmu-miR-183-5p were up-regulated, whereas mmu-miR-26a-5p, mmu-miR-26b-5p and mmu-miR-32-5p were down-regulated (p < 0.05). To verify these results, the iMC23 mouse melanocytes were used. Transfection of iMC23 cells with specific miRNAs mimics or inhibitors or with 3'UTR reporter clone of MITF, showed only mmu-miR-183-5p binds to 3'UTR of MITF mRNA and regulates its expression in iMC23 melanocytes. In conclusions, this is the first study shows that miR-183-5p is a direct regulator of MITF in iMC23 melanocytes. Thus, miR-183-5p is an important regulator of melanocytes homeostasis and may be a novel target for autoimmune depigmentation therapy.

Missense, silent, non-sense and frame-shift mutations in exon 3 of the filaggrin gene in patients with bronchial asthma, atopic dermatitis, allergic rhinitis and mixed atopy.

This study investigated the atopic march on the basis of genetics. This research detected 227 variants in the filaggrin gene (FLG gene). Missense, silent, non-sense, frame-shift and non-coding mutations were detected in exon 3 of the FLG gene in patients with bronchial asthma, atopic dermatitis, allergic rhinitis and mixed atopy. Missense mutation was detected at c.8343 G > C (p. Asp2781Glu) in all adult asthmatic and allergic rhinitis patients. Whereas, mutation at c.8360 C > T/A (p. Arg2787 His/Leu) was detected in all childhood asthmatic and mixed atopic patients. A non-coding mutation was detected at c.12365 in atopic dermatitis and bronchial asthma patients. Furthermore, DNA sequencing of asthmatic and mixed atopic patients showed missense mutations at c.6073 C > T (p. Gly2025Glu) and a silent mutation at c. 8341 G > A (p. Asp2781Asp).

Autoimmune response against tyrosinase induces depigmentation in C57BL/6 black mice.

Regulation of melanogenesis by tyrosinase has now become an attractive approach for treatment of vitiligo but still the role of tyrosinase in the induction of depigmentation remains largely unexplored. This study was explored the role of tyrosinase in the induction of autoimmune depigmentation in C57BL/6 mice. Depigmentation was induced in C57BL/6 mice by tyrosinase immunization. Induced depigmentation was characterized by visual detection and was verified by histopathological analysis of lesional and non-lesinal skin biopsies. Moreover, induced depigmentation was re-validated by gene expression analysis of vitiligo-relevant genes by Taqman assays. Immunization of C57BL/6 mice by tyrosinase induces depigmentation on hairs as well as on skin. Immunoassays with Protein A-purified immune IgGs showed high titre antibodies against tyrosinase. Histopathological analysis showed that the total melanocytes were depleted from the basal layer of the epidermis and also from the dermis of depigmented lesions. The gene expression of vitiligo-relevant genes TYRP1, DCT, MLANA, MCIR, POMC, FOXJ2, CSNK1G3, SOX10, PMEL and KIT was significantly low in lesional skin as compared with non-lesional skin (p < .05). In contrast, the mRNA expression of CASP3 and NFκB1 was significantly high in lesional skin of depigmented mice as compared with non-lesional skin (p < .05). Furthermore, involvement of cellular immunity in depigmentation was confirmed by the reduction of CD4+:CD8+ lymphocytes ratio. In conclusion, this study shows that the autoimmune response against tyrosinase induces depigmentation in black C57BL/6 mice. The data obtained from the lesional and non-lesional skin biopsies showed the same features as were reported in human vitiligo patients.

TNF-α - 308 G/A and IFN-γ + 874 A/T gene polymorphisms in Saudi patients with cutaneous leishmaniasis.

BACKGROUND: Cutaneous leishmaniasis (CL) is well linked with immunogenetic factors. This study was undertaken to test the association of TNF-α - 308 and IFN-γ + 874 gene polymorphisms with the susceptibility of Leishmania (L) species among CL patients in central region of Saudi Arabia. METHODS: This is a case-control study involved 169 Saudi subjects with different L. species and 199 healthy controls from central region of Saudi Arabia. All subjects were characterized by TNF-α - 308 G/A and IFN-γ + 874 A/T gene polymorphisms using PCR. RESULTS: Evaluation of genotyping and allelic frequency of TNF-α - 308 G/A in different L. species showed no significant association compared to controls (p > 0.05). Except, in cases of L. tropica that showed significantly higher TNF-α - 308 A versus G allele frequency (p = 0.0004). Evaluation of genotyping of IFN-γ + 874 (TT versus AA+AT recessive) and allelic frequency of IFN-γ + 874 (T versus A) showed significant higher in L. major and also in total CL cases as compared to healthy controls (p < 0.05). Furthermore, a strong association was observed between the susceptibility of L. major, L. tropica or total CL cases with synergistically combined high TNF-α 308/INF-γ 874 alleles. CONCLUSIONS: This is the first report that shows the gene polymorphisms of TNF-α - 308 G/A and IFN-γ + 874 A/T in Saudi patients with different L. species infections. Data showed that the TNF-α-308 G/A gene polymorphism is not associated with the susceptibility of CL in Saudi subjects. The only correlation was found in between A versus G allelic frequency in L. tropica. Importantly, IFN-γ + 874 A/T polymorphism was found to be associated with the susceptibility of L. major and also with total CL subjects. Moreover, data from synergistically combined high TNF-α 308/INF-γ 874 alleles strongly suggest their potential role in the susceptibility of leishmania infection.

Prevalence of Leishmania species among patients with cutaneous leishmaniasis in Qassim province of Saudi Arabia.

BACKGROUND: Leishmaniasis is a parasitic infection endemic in more than ninety countries of the world. The cutaneous leishmaniasis (CL) is a most common form of leishmaniasis and it remains to be a major public health issue in Saudi Arabia. This study was undertaken to investigate the Leishmania species responsible for CL infection in different provinces of Qassim, Saudi Arabia. METHODS: Skin biopsies were obtained from CL patients and DNA was extracted using the Magna pure system. Leishmania species were identified by highly specific/sensitive quantitative and qualitative PCR. RESULTS: Out of total 206 CL biopsies, 49.5% biopsies were found to be positive for Leishmania major (L. major), 28.6% biopsies were positive for Leishmania tropica (L. tropica), 3.9% were found to be positive for Leishmania infantum/donovani (L. infantum/donovani). Not only have these, all tested CL biopsies showed negative test for Leishmania mexicana (L. mexicana) and Leishmania viannia (L. viannia). CONCLUSIONS: This is the first comprehensive study that shows the majority of CL in Qassim was caused by L. major and L. tropica. To the best of our knowledge, this is the very first report that shows the occurrence of L. infantum/donovani in Saudi Arabia. This requires higher alert to the Ministry of Health of Saudi Arabia to take proactive actions in preventing the onset of L. major, L. tropica, L. infantum and L. donovani infections.

Filaggrin, major basic protein and leukotriene B4: Biomarkers for adult patients of bronchial asthma, atopic dermatitis and allergic rhinitis.

Bronchial asthma (BA), atopic dermatitis (AD), and allergic rhinitis (AR) are well known atopic disorders with complex etiologies. This study was undertaken to investigate the role of filaggrin, eosinophil major basic protein (MBP) and leukotriene B4 (LTB4) in patients with BA, AD, and AR. Sera from 1,246 patients with different atopic disorders and 410 normal healthy controls were collected and were evaluated for filaggrin, MBP and LTB4 by specific sandwich ELISAs, whereas immunoglobulin E (IgE) was used as a positive control for atopic patients. Serum analysis showed that filaggrin levels were remarkably high in patients with AD and in patients with multiple (mixed) atopic disorders (p < 0.001), whereas its levels in BA and AR patients were low but much higher than in normal human sera (p < 0.01). MBP levels were also high in AR, BA and mixed atopic patients, whereas AD patients showed no increase of MBP (p > 0.05). In contrast, LTB4 level was found to be significantly low in all tested atopic patients groups as compared to the levels of LTB4 present in normal human sera (p < 0.001). In conclusion, these findings support an association between filaggrin, MBP or LTB4 and atopic disorders. Our data strongly suggest that filaggrin, MBP or LTB4 might be useful in elucidating the mechanisms involved in the pathogenesis of these atopic disorders.

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.

Association of psychological stress with skin symptoms among medical students.

OBJECTIVES: To evaluate the association between psychological stress and skin symptoms among medical students.  Methods: A cross-sectional study was carried out between January and June 2015. Electronic survey consists of Perceived Stress Questionnaire (PSQ) and Self-Reported Skin Complaints Questionnaire were distributed to all 1435 undergraduate students at College of Medicine, King Saud University (KSU), Riyadh, Saudi Arabia. Results: Final analysis was performed on data from 529 (36.9%) students. Students were divided into three groups: least stressed students, n=135, PSQ index less than 0.39; highly stressed students, n=136, PSQ index greater than 0.61; and moderately stressed students, n=258. Older age, female gender, during exam weeks, and fourth and fifth years of medical school (all p less than 0.01) were associated with the highest perceived stress levels. When compared to least stressed students, highly stressed students suffered from more oily, waxy patches or flakes on scalp (p≤0.0001), dry/sore rash (p≤0.0001), warts (p≤0.0001), pimples (p≤0.0001), itchy skin (p≤0.0001), hands itchy rash (p≤0.0001), hair loss (p≤0.0001), pull-out own hair (p=0.008), scaly skin (p=0.012), troublesome sweating (p=0.016), nails biting (p=0.028), and other rashes on face (p= 0.028).  Conclusion: Various common skin conditions could appear in context of psychological stress among medical students.

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.

Altered expression of intracellular Toll-like receptors in peripheral blood mononuclear cells from patients with alopecia areata.

BACKGROUND: Toll-like receptors (TLRs) are pattern-recognition-receptors that sense a variety of pathogens and initiation of innate and adaptive immune responses. This study was undertaken to investigate the expression of TLRs in peripheral blood-mononuclear cells (PBMCs) of AA patients and to determine whether TLR-mediated inflammatory signals are important for the perspective of AA management. METHODS: Gene expression of TLRs and T-helper (Th) type-1, Th-2, Th-17 and regulatory T-cell cytokines in PBMCs was quantified by TaqMan Assays. Production of these cytokines in serum samples was determined by sandwich ELISAs. RESULTS: All TLRs (TLRs 1-10) were expressed in PBMCs of AA patients. Importantly intracellular TLRs (TLRs 3, 7, 8 and 9) were significantly up-regulated in AA patients as compared with controls (p < 0.05). Interleukin (IL)-2, TNF-α, and IL-17A gene expression in patients' PBMCs and their secretion in patients' sera were significantly higher as compared with their respective controls (p < 0.05). Whereas, TGF-ß gene expression in patients' PBMCs and TGF-ß protein level in patients' sera were significantly lower as compared with their controls (p < 0.05). CONCLUSION: This is the first report that shows the comprehensive expression profile of TLRs in AA patients. We conclude that up-regulated expression of intracellular TLRs in PBMCs of AA patients may play an active role in abnormal regulation of Th-1, Th-17 and regulatory T-cell cytokines in alopecia areata. GENERAL SIGNIFICANCE: Targeting of TLRs and their associated inflammatory signaling will open new areas of research; this may lead to the development of novel therapeutic targets for the treatment of AA or other skin disorders.

Immunoglobulin e, interleukin-18 and interleukin-12 in patients with atopic dermatitis: correlation with disease activity.

INTRODUCTION: Atopic dermatitis (AD) is a chronic inflammatory skin disorder. Immunological/inflammatory reactions are reported to play a role in AD but their role in disease activity has not been fully investigated. This study was done to investigate the role of immunoglobulin E (IgE), interleukin (IL)-18 and IL-12 in AD patients with different disease severities. MATERIALS AND METHODS: Sera from 50 AD infants with varying levels of disease activity according to the scoring index of atopic dermatitis (SCORAD) index and 30 age-matched healthy controls were evaluated for serum levels of IgE, IL-18 and IL-12/p40. RESULTS: Serum analysis showed higher levels of IgE, IL-18 or IL-12/p40 in AD patients compared with controls. Interestingly, not only was there an increased number of subjects positive for IgE, IL-18 or IL-12/p40, but also the levels of these parameters were higher among AD patients whose SCORAD scores were higher. In addition, a significant correlation was observed between the levels of these parameters and SCORAD scores. CONCLUSION: These findings support an association between IgE, IL-18 or IL-12/p40 and AD. The stronger response observed in serum samples from patients with higher SCORAD scores suggest that IgE, IL-18 and IL-12/p40 may be useful in evaluating the progression of AD and in elucidating the mechanisms of disease pathogenesis.

Interleukin-4 -590 T>C and interleukin-4 receptor Q551R A>G gene polymorphisms in Saudi cases with alopecia areata.

OBJECTIVES: Immunogenetic factors are known to play a role in the pathogenesis of alopecia areata (AA). This study aimed at investigating the association between AA with the polymorphisms of interleukin-4 (IL-4) promoter and receptor (IL-4R) genes. PATIENTS AND METHODS: This work is a case-control study that was conducted on 76 AA patients from Qassim region, Saudi Arabia. Patients were compared with 93 normal healthy controls from the same locality. Genomic DNA was extracted and processed using real-time PCR amplification for characterization of IL-4 -590 T>C and IL-4R Q551R A>G gene polymorphisms. RESULTS: Cases of AA showed a higher frequency of the IL-4 -590 CC homozygous genotype compared with controls (63.2 vs. 53.8%, P>0.05) with a lower frequency of the TT genotype (5.3 vs. 10.8%); yet, both were statistically nonsignificant (P>0.05). Regarding the IL-4R Q551R A>G polymorphism, cases and controls showed nearly equal frequencies of all variants, that is, with no significant difference. Although the frequency of the IL-4 C and the IL-4R A alleles was higher among cases than among controls (78.9 vs. 71.5% and 78.8 vs. 72.6%, respectively), this was also statistically nonsignificant (P>0.05). Comparing case subgroups in terms of their age of onset, sex, disease severity, consanguinity, and family history showed no statistically significant difference regarding the studied genetic variant. CONCLUSION: IL-4 -590 and IL-4R Q551R gene polymorphisms are not associated with the susceptibility and the clinical pattern of AA in Saudi patients. We recommend further research studies involving the estimation of cytokines both in the serum and in the local skin lesions or in cultured skin cells to figure out whether Th1 or Th2 pathways play a specific role in the pathogenesis of AA.

Genetic polymorphisms of NFκB1 -94 del/ins ATTG, NFκB1A 2758 A>G and SUMO rs237025 G>A in psoriasis.

BACKGROUND: Nuclear factor-κB (NF-κB) and small ubiquitin-like modifier (SUMO4) are key transcription factors involved in the regulation of immune responses and apoptosis. The aim of this study is to test for the association of NF-κB and SUMO gene polymorphisms with the susceptibility and severity of psoriasis among Saudi cases. SUBJECTS AND METHODS: This is a case controlled study including 85 Saudi psoriasis patients in addition to 92 matched healthy unrelated controls from the same locality. For all participants, DNA was analyzed by PCR for characterization of NF-κB1 -94 del/ins ATTG, NF-κB IA 2758 A>G and SUMO rs237025 G>A gene polymorphisms. RESULTS: Compared to controls, psoriasis patients showed a non-significant difference for all frequencies of genotypes and alleles of NF-κB1 ins/del, NF-κB1A A>G and SUMO4 G>A polymorphisms (p>0.05). However, cases with the plaque type had significantly higher frequency of the SUMO4 A allele carriage (GA+AA genoytpes) than the guttate type (78.6% vs. 21.4%, p=0.02). The PASI score was also significantly higher among cases with the NF-κB1A AA genotype than other cases (p=0.00). CONCLUSION: Genetic polymorphisms of NF-κB1-94 ins/del ATTG, NF-κB IA 2758 A>G and SUMO4 rs237025 G>A were not associated with the susceptibility to psoriasis vulgaris in Saudi patients. However, it might be associated with the expressivity of the disease in terms of its clinical type and severity.

Onychomycosis in qassim region of saudi arabia: a clinicoaetiologic correlation.

BACKGROUND: Onychomycosis is mainly caused by dermatophytes, but yeasts and nondermatophyte molds have also been implicated, giving rise to diverse clinical presentations. The aetiological agents of the disease may show geographic variation. AIM: The aim of the present study was to isolate the causative pathogens and to correlate the various clinical patterns of onychomycosis with causative pathogens. MATERIALS AND METHODS: The study population comprised 170 patients with clinical suspicion of onychomycosis. Nail samples were collected for direct microscopic examination and culture. Clinical patterns were noted and correlated with causative pathogens. RESULTS: Out of total 170 cases included in the study, 140 (82.4%) were positive by microscopy and 77 (45.3%) showed positive mycological findings by both microscopy and culture. The male: female ratio was 1:2.5 and the mean age was 35.29 ± 16.47 years. Fingernails were involved in 51.9%, toenails in 28.6% and both fingernails and toenails in 19.5% of the 77 patients. The clinical types noted were distal lateral subungual onychomycosis (71.4%), proximal subungual onychomycosis (10.4%), total dystrophic onychomycosis (10.4%), superficial white onychomycosis (3.9%) and mixed pattern onychomycosis (3.9%). Yeasts were the most common pathogens isolated, being found in 36 patients (46.8%) followed by nondermatophyte molds which were isolated from 28 patients (36.4%) followed by dermatophytes which were isolated from 13 patients (16.9%). CONCLUSION: Distal lateral subungual onychomycosis was the most common clinical presentation. Candida albicans, Aspergillus species and Tricophyton rubrum were the major pathogens. A single pathogen can give rise to more than one clinical type.

Preferential recognition of hydroxyl radical-modified superoxide dismutase by circulating autoantibodies in patients with alopecia areata.

BACKGROUND: Alopecia areata (AA) is a common form of localized, non-scarring hair loss. The cause of AA is unknown but reports suggest an autoimmune etiology, where oxygen free radicals play an important role. OBJECTIVE: The aim of this study was to investigate the role of a hydroxyl radicals (·OH)-modified antioxidant enzyme, superoxide dismutase (SOD), in AA autoimmunity. METHODS: SOD was modified by ·OH radicals. Binding characteristics of autoantibodies in AA patients (n=26) against ·OH-modified SOD (·OH-SOD) were evaluated by immunoassays and the results were compared with those of healthy, age-matched controls (n=30). The effects of ·OH radicals on immunoglobulin G (IgG) isolated from AA patients were studied. RESULTS: Highly specific binding to ·OH-SOD was observed in 32% of the samples of patient sera, whereas normal human sera showed negligible binding with either antigen. Competitive inhibition immunoassays reiterated the results from direct binding. Protein-A-purified IgG from AA patients (AA-IgG) also showed strong binding to ·OH-SOD as compared to IgG from normal human controls (p<0.001). In addition, AA-IgG from patients with alopecia universalis recognized ·OH-SOD to a greater extent than did AA-IgG from patients with the patchy, persistent type of alopecia. Furthermore, sera from AA patients had lower levels of SOD activity as compared to control sera. CONCLUSION: This is the first report showing an association between ·OH-modified SOD and AA. These novel results demonstrate that ·OH radical-mediated changes in SOD present unique neo-epitopes that might contribute to antigen-driven antibody induction in AA.

Association of CYP2C9 Genetic Variants with Vitiligo.

BACKGROUND: Vitiligo is a depigmenting skin disorder in which genetic factors play an important role. OBJECTIVE: To examine the association of CYP2C9 (*) 1/(*) 2/(*) 3 gene polymorphism with vitiligo. METHODS: In this case controlled study, 95 Saudi patients with vitiligo (50 men and 45 women), with a mean age of 27.3 years, were analyzed. Patients were compared to 86 healthy controls from the same locality (76 men and 10 women), with a mean age of 20.1 years. In all participants, DNA was extracted and processed for characterization of 2C9 (*) 1/(*) 2/(*) 3 gene variants using real time-polymerase chain reaction. RESULTS: Vitiligo patients have a significantly higher CYP2C9 (*) 3 allele carriage rate compared to controls (32.7% versus 4.7%, p=0.00, odds ratio=9.9, 95% confidence interval=3.3~29.6). On the other hand, frequencies of CYP2C9 (*) 2 genotypes and alleles did not show any significant difference between vitiligo cases and controls. When the frequencies of CYP2C9 genotypes were compared among subgroups of age, gender, family history, and disease patterns, the cases with positive consanguinity had significantly higher frequencies of homozygous genotypes than others (p=0.029). CONCLUSION: CYP2C9 (*) 3 allele carriage is probably associated with vitiligo susceptibility.

Impact of atopic dermatitis on the quality of life of Saudi children.

OBJECTIVE: To assess the impact of atopic dermatitis (AD) on the quality of life (QoL) of Saudi infants and children using a validated/culturally adapted Arabic version of the infants` dermatitis quality of life (IDQoL) index, and to investigate the correlation between IDQoL and disease severity. METHODS: This study was performed in the Dermatology Clinics and Hospitals affiliated to Qassim University, Buraidah, Saudi Arabia between September 2012 and August 2013. The study was designed to investigate the role of IDQoL in AD patients with different severities. The AD patients (n=630) were evaluated for IDQoL and disease severity using the SCORing of Atopic Dermatitis index. RESULTS: The average (+/=standard deviation) of IDQoL score was 12.3+/=5.1 for all studied subjects. The IDQoL scores were significantly different among the 3 studied severity groups, with a highest score in the severe group (p=0.000). A positive correlation was observed between the severity of AD and IDQoL scores (r=0.596, p=0.000). Three items with a negative impact on IDQoL were itching and scratching, the child`s mood, and time to get the child to sleep. All these reached a significantly higher value in the severe group compared with the moderate or mild groups (p=0.000). No significant differences were observed concerning gender or the association with other atopic disorders (p=0.99, and p=0.79). CONCLUSION: This study demonstrates that AD manifestations impaired the IDQoL of Saudi patients and were also well correlated with the disease severity score.

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.

Acquired immunogenicity of DNA after modification with malondialdehyde in patients with alopecia areata.

BACKGROUND: Lipid peroxidative-mediated reactions have been implicated in alopecia areata (AA). However, the potential for lipid peroxidation to elicit an autoimmune response or to contribute in disease pathogenesis remain unexplored. This study was undertaken to investigate the status/contribution of lipid oxidative-by-product malondialdehyde modified DNA (MDA-DNA) in AA. METHODS: DNA was modified by MDA. Binding characteristics of AA circulating immunoglobulin G (AA-IgG) MDA-modified DNA were screened. Immunogenicity of MDA-DNA was probed by inducing antibodies in rabbits. DNA samples from AA patients were isolated (DNA-AA) and their immune reactions with rabbit anti-MDA-DNA-IgGs were evaluated. RESULTS: Our data show that MDA caused extensive DNA damage. Protein-A purified IgG from 45% of AA patients showed strong binding to MDA-DNA in comparison with native DNA (p < 0.05). MDA-DNA was found to be highly immunogenic in rabbits. Rabbit anti-MDA-DNA-IgG showed binding with isolated DNA from AA patients. CONCLUSIONS: This is the first study to demonstrate the role of MDA-modified DNA in AA patients. Our novel results conclude that perturbations in DNA by MDA present unique neo-epitopes that might be one of the factors for the antigen driven antibodies induction in AA. These results provide an important insight into the immunological mechanisms occurring in AA.

Pattern of bacterial colonization of atopic dermatitis in saudi children.

BACKGROUND: Atopic dermatitis is an inflammatory skin disorder. Although it is not a life threatening condition, it may become infected with microorganisms, especially in children. OBJECTIVES: The aim of this study was to determine bacterial colonisation in children with atopic dermatitis. METHODS: A total of 80 children were randomly included in this study. Two swabs were taken from each child, one from the eczematous skin lesion and the other from apparently healthy skin, as a control. Bacteria were isolated and identified on the basis of the colonial morphology, gram staining and the Vitek System. RESULTS: The mean age of children in this study was 1.4 years, with no gender difference (p=0.98) (n=80). A total of 240 bacterial colonies were grown from atopic dermatitis lesions in contrast to 193 colonies from non-lesional skin. Gram-positive cocci were found in 78 (97.5%) lesions and in 77 (96.2%) non-lesional skin. Staphylococci species were significantly detected in the lesions than in the non-lesional skin. Ent. Faecalis, Ent. Faecium, Ent. gallinarium and C. minutissium were significantly isolated from lesions as compared to non-lesional skin, whereas C. xerosis was insignificantly found to be more in the lesions (p=0.21). Gram-negative bacteria were isolated from 7(8.8%) lesions, but none were isolated from non-lesional skin. Recovered species were Pantoea agglomerans, Enterobacter cloacae, Chryseobacterium indologenes and Acinetobacter Iwoffii. CONCLUSION: Atopic dermatitis in children is complicated with streptococcal and gram-negative bacterial colonisations and the latter was correlated with the severity of the lesions. Enterococci and Corynebacterium species were significant residents. S. aureus remained the chief inhabitant. No causal relationship could be established between the skin microbiota and atopic dermatitis.