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.

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.

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.

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.

4-Hydroxy-2-nonenal modified histone-H2A: a possible antigenic stimulus for systemic lupus erythematosus autoantibodies.

Protein modifications by 4-hydroxy-2-nonenals (HNE) are involved in various diseases. Histones are DNA protective nucleoprotein, which adopt different structures under oxidative stress. This study was undertaken to test the role of HNE-modified-histone-H2A (HNE-H2A) in systemic lupus erythematosus (SLE). Our data revealed that HNE-mediated-lipid peroxidation in histone-H2A caused alteration in histidine, lysine and cystein residues. In addition, protein carbonyl contents were also high in HNE-H2A. HNE-specific quencher, L-carnosine further reiterates HNE-modifications. Specificity of autoantibodies from SLE patients (n=48) were analyzed towards HNE-H2A and their results were compared with sex- and age-matched controls (n=36). SLE autoantibodies show preferential binding to HNE-H2A in comparison with histone-H2A (p<0.0001). Furthermore, HNE-H2A was also detected in SLE peripheral blood mononuclear cells. In conclusion, this is the first study to demonstrate the role of HNE-modified-histone in SLE. Preferential binding of HNE-H2A by affinity purified SLE-IgG pointed out the likely role of HNE-H2A in the initiation/progression of SLE.

Immunological studies of reactive oxygen species damaged catalase in patients with systemic lupus erythematosus: correlation with disease activity index.

OBJECTIVES: This study was undertaken to investigate the status and contribution of oxidized catalase in systemic lupus erythematosus (SLE) and to explore whether oxidized catalase has a role in disease progression. METHODS: Catalase (CAT) was modified by reactive oxygen species (ROS). Sera from 50 SLE patients with varying levels of disease activity according to SLE Disease-Activity-Index (SLEDAI) and 45 age- and sex-matched healthy controls were evaluated for antibodies against oxidized CAT. RESULTS: Serum analysis showed significantly higher level of anti-oxidized-CAT-antibodies in SLE patients compared with controls. Interestingly, not only was there an increased number of subjects positive for anti-oxidized-CAT-antibodies, but also the levels of these antibodies were significantly higher among SLE patients, whose SLEDAI scores were ≥ 10 as compared with lower SLEDAI scores (<10). In addition, significant correlation was observed between the levels of anti-oxidized-CAT-antibodies and SLEDAI score (r = 0.796). Furthermore, sera from SLE patients had lower levels of CAT activity compared with control sera. CONCLUSIONS: These findings support an association between oxidized CAT and SLE. The stronger response observed in serum samples from patients with higher SLEDAI scores suggests that oxidized CAT may be a useful biomarker in evaluating the progression of SLE and in elucidating the mechanisms of disease pathogenesis.

Biochemical markers of oxidative and nitrosative stress in acne vulgaris: correlation with disease activity.

BACKGROUND: Acne vulgaris is a multifactorial skin disorder of unknown etiology. Free radical-mediated reactions have been implicated but their role in eliciting this response and contributing to disease progress remains unexplored. This study was undertaken to investigate the status and contribution of oxidative/nitrosative stress in patients with acne vulgaris. METHODS: Sera from 50 acne vulgaris with varying levels of disease activity (mild, moderate, and severe) according to the Global Acne Grading System (GAGS) and 40 age- and sex-matched controls were evaluated for serum levels of oxidative/nitrosative stress markers, including protein oxidation, lipid peroxidation and nitric oxide (NO), superoxide dismutase (SOD), and glutathione (GSH). RESULTS: Serum analysis showed significantly higher levels of carbonyl contents, malondialdehyde (MDA) and NO, in acne patients compared with healthy controls (P < 0.05). Interestingly, not only there were an increased number of subjects positive for carbonyl contents, but also the levels of these oxidants were significantly increased with the increase of the disease activity (P < 0.05). In addition, a significant correlation was observed between the levels of carbonyl contents and the GAGS scores (r = 0.341, r = 0.355, and r = 0.299, respectively). Furthermore, sera from acne patients had lower levels of SOD and GSH compared with healthy control sera. CONCLUSION: These findings support an association between oxidative/nitrosative stress and acne. The stronger response observed in serum samples from patients with higher GAGS scores suggests that markers of oxidative/nitrosative stress may be useful in evaluating the progression of acne and in elucidating the mechanisms of disease pathogenesis.

Psoriasin: a novel marker linked obesity with psoriasis.

To evaluate the role of psoriasin, koebnerisin, interleukn (IL)-12 and IL-23 in the pathogenesis of psoriasis and their relations to Psoriasis Area Severity Index (PASI) and obesity. Thirty patients had chronic plaque psoriasis and 30 healthy subjects matched in age and sex were enrolled in this study. Serum from all subjects were used for determination of psoriasin, koebnerisin, IL-12 and IL-23 by ELISA kits. IL-23 and psoriasin were significantly higher in skin psoriasis compared to controls and psoriatic arthritis (PsA). There was a correlation between psoriasin and both PASI and obesity. On the other hand, IL-12 was significantly increased in PsA compared to skin psoriasis (p=0.000) and controls. Its sensitivity and specificity were 87%, 93%; respectively. To our knowledge, psoriasin is the first biomarker confirm the link between obesity and psoriasis. The risk of developing psoriasis is directly related to higher BMI.

Patients seen at the Dermatology ambulatory office in a tertiary care center in Qassim region, Saudi Arabia.

BACKGROUND: In Saudi Arabia where there is lack of dermatologists in primary health care centers, patients with simple or minor skin conditions have to attend to hospitals to be treated. We analyzed the data of patients with cutaneous disorders attending the tertiary referral hospital in Qassim region of Saudi Arabia, with the aim to identify the most common conditions that patients complain of, in order to define the areas where the education of General Practitioners in Dermatology must focus. METHODOLOGY: All patients seen at the Dermatology ambulatory office in the Emergency Department of Qassim University affiliated hospital from January 2011 to December 2011 were included in this retrospective analysis. The medical records of the patients (history, physical examination and laboratory investigations) were analyzed to ascertain the diagnosis and the management of cases. All patients were evaluated by qualified dermatologists. RESULTS: A total of 1147 patients attended the Dermatology ambulatory office. Most patients were young adults in the age group 21-30 years (34.4%). Allergic skin diseases (65.2%), mostly dermatitis (48.8%) and urticaria (10.5%) were the most common for attendance, followed by infectious diseases (25.8%) and inflammatory and autoimmune disorders (5.3%). The management of the vast majority of cases (94.1%) consisted of systemic treatment and 58.2% patients required topical treatment. A reevaluation plan as outpatients was planned in 9.0% patients while only 0.3% of patients required admission in the hospital. CONCLUSION: Allergic and infectious skin diseases were the most common cutaneous diseases in patients attending this tertiary University hospital, while the management of most patients did not require specialized care. On the basis of the present data, the training of primary health care providers in Dermatology should emphasize these common conditions, with the aim of improving primary care and alleviating the burden on hospital care.

Documentation of vancomycin-resistant Staphylococcus aureus (VRSA) among children with atopic dermatitis in the Qassim region, Saudi Arabia.

INTRODUCTION: Staphylococcus aureus is known as a common pathogen in atopic dermatitis. A methicillin-resistant S. aureus strain with reduced susceptibility to vancomycin (VISA/VRSA) is increasing worldwide. The aims of this study were to evaluate the antibiotic-susceptibility pattern of S. aureus isolated from children with atopic dermatitis and to identify the occurrence of resistance to glycopeptide antibiotics. METHODS: Swabs were collected from atopic dermatitis skin lesions of 80 children being treated at dermatology clinics whose ages ranged from 6 months to 15 years in the period from March 2009 to February 2010. Isolates were studied with an antibiogram for an antibiotic-susceptibility test. The selected antibiotics were the usually administered antimicrobials at dermatological clinics in Buraydah (Qassim, Saudi Arabia). Results were determined as minimal inhibitory concentration (MIC) using the Vitek system. RESULTS: Thirty S. aureus isolates showed resistance to streptomycin (100%), benzylpenicillin and ampicillin (96.7%), and oxacillin (90%). S. aureus resistance to trimethoprim/sulfamethoxazole, tigecycline, and vancomycin was 63.3%, 83.3%, and 53.3%, respectively. Resistance to linezolid was less, at 5.7%. CONCLUSIONS: Strains of MRSA with decreasing susceptibility to vancomycin were documented in the Qassim region of Saudi Arabia. Other studies will be required on VISA/VRSA strains concerning phenotypic and genotypic characterization.

Preferential recognition of peroxynitrite damaged thymidine-monophosphate by anti-DNA autoantibodies in systemic lupus erythematosus.

This study was undertaken to investigate the role of peroxynitrite (ONOO(-)) modified thymine-5'-monophosphate (TMP) in the generation of anti-DNA autoantibodies in patients with systemic lupus erythematosus (SLE). TMP was exposed to ONOO(-) in vitro and challenged in vivo. TMP and ONOO(-)-modified-TMP were found to be nonimmunogenic in rabbits. TMP-linked-BSA and ONOO(-)-modified-TMP-BSA induced high titer antibodies. Induced antibodies against ONOO(-)-TMP-BSA show crossreactions with nucleic acids conformers. A high degree of specific binding by SLE autoantibodies with ONOO(-)-TMP-BSA was observed. Our novel results provide an important insight into the immunological basis of anti-DNA autoantibodies generation in SLE.