Circadian clock gene expression and polymorphism in non-segmental vitiligo.

BACKGROUND: Vitiligo is an acquired and progressive mucocutaneous disease with the damage of functioning epidermal melanocytes. Metabolic syndrome is associated with inflammatory skin diseases incorporating vitiligo. The circadian dysfunction triggers the pathogenesis of metabolic diseases, so our study aimed to determine the relationship between aryl hydrocarbon receptor nuclear translocator-like gene, a ligand-activated transcription factor and sensor of environmental chemicals, expression and polymorphism with non-segmental vitiligo, as well as its effect on lipid profile. METHODS: This case-control study was handled on 50 non-segmental vitiligo patients (generalized (12) and localized type (focal; 24 and acrofacial; 14)) and 50 matched controls. Each subject was proposed for full history taking, clinical examinations, serum lipid profile, and measurement of BMAL1 gene expression in the blood, and BMAL1 rs2279287 polymorphism of DNA extract from whole blood by real time-PCR. RESULTS: We identified that total cholesterol, triglyceride, and low-density lipoprotein were significantly higher, but high-density lipoprotein was significantly lower in non-segmental vitiligo patients than in the control group. A significant increase in circadian gene expression in non-segmental vitiligo patients was observed, with more detection of the BMAL1 T/C genotype (92%) than the T/T genotype. There was a significant positive relationship between the level of the circadian gene and the vitiligo patient's age, age of onset, and VIDA Score. The level of the circadian gene at Cutoff  ≥ 1.16 can predict the prognosis of vitiligo with a sensitivity of 78%, specificity of 84%, and accuracy of 81%. CONCLUSION: The circadian gene has an active role in the progress of non-segmental vitiligo and targeting this gene could have a significant impact on its management.

Immunohistochemical Expression of Angiotensin-Converting Enzyme 2 in the Skin of Patients Affected by COVID-19.

BACKGROUND: After many recorded cases of acute pneumonia of unknown cause, the World Health Organization announced COVID-19 as the start of a new coronavirus disease pandemic in 2019. Angiotensin-converting enzyme-2 (ACE2) is reduced by a protease known as transmembrane serine type 2 in the host cell, which then activates the S protein of SARS-CoV-2 regulating coronavirus entry into the host cells. AIM: The aim of this study was to assess the immunohistochemical expression of ACE 2 in the skin of patients affected by COVID-19 with and without cutaneous manifestations and to correlate ACE2 expression with clinical and pathologic parameters. METHODS: Skin biopsies were obtained from skin lesions of 25 patients presenting with cutaneous manifestations and from the left forearm of 22 patients without cutaneous manifestations. The specimens were processed for evaluation of histopathologic changes and ACE2 immunohistochemical evaluation. RESULTS: Positive ACE2 expression was significantly higher in patients without cutaneous manifestations (96%) than those with cutaneous manifestations (72.7%). Positive ACE2 expression in the skin of affected patients was significantly associated with the presence of comorbidities, positive family history, high ABCD score, elevated lactate dehydrogenase, high D-dimer, rapid respiratory rate, and low oxygen saturation. CONCLUSIONS: The skin could be involved in COVID-19 infection in the form of inflammatory changes, such as pityriasis rosea-like lesions. Patients with COVID-19 who presented with cutaneous manifestations are usually less severe. The presence of ACE2 in the skin of patients with COVID-19 is an indicator of worse status. Patients with COVID-19 without skin manifestations showed higher positivity for ACE2, which may explain the severity of the cases.

Identifying the association between polymorphisms in the GZMB and IFIH1 genes and psoriasis in Egyptians.

OBJECTIVES: This study aims to examine whether the genetic variants in the genes for Granzyme B (GZMB) and Interferon Induced with Helicase C domain 1 (IFIH1) were associated with psoriasis. BACKGROUND: Psoriasis, a papulosquamous skin disease, was initially thought of as a disorder primarily of epidermal keratinocytes but is now recognized as one of the most common immune-mediated disorders. It is caused by the interplay between multiple genetic and environmental risk factors. SUBJECTS AND METHODS: This case-control study has 65 participants with psoriasis and 65 healthy controls. Real-time PCR was used to genotype GZMB (rs8192917) and IFIH1 (rs35667974). RESULTS: Genotype occurrence and allelic spreading for both SNPs are in Hardy - Weinberg equilibrium. The genotype and allele distributions of rs35667974 showed no differences between the studied groups. Regarding rs8192917, compared to Group II, there is a statistically significant rise in the CC genotype and C allele in Group I. Higher PASI scores are detected in the C/C and C/T genotypes more than the T/T genotype. Univariate and multivariate analyses revealed that BMI, catalase, MDA, and rs8192917 (C/C) are associated with psoriasis. CONCLUSION: GZMB rs8192917 was significantly related to psoriasis risk; its C allele is likewise associated with psoriasis vulnerability. However, our investigation found no link between rs35667974 and psoriasis.

Interleukin-6 serum level and gene polymorphism in keloid patients.

The formation of keloid is associated with accumulation of extracellular matrix (ECM) formed mainly of collagen and fibronectin. Persistent deregulated IL-6 synthesis causes the development of various diseases. This study aim to investigate interleukin 6 (IL-6) serum level and gene polymorphism in a sample of Egyptian patients having keloid. This study was carried out on 90 subjects; 60 patients with keloid, and 30 age and sex matched apparently healthy control. All subjects underwent full history taking, clinical examinations, weight and length measuring to calculate BMI, dermatological examination, analysis of IL6-572 gene polymorphism using REFLP- PCR and IL-6 serum level using ELISA.IL-6 serum levels were significantly higher in keloid patients than control group (75.54±39.18) vs (19.17±6.06), (p <0.001). The higher serum levels of IL-6 were associated with GG genotype (104.84±19.12) followed by CG (57.64±35.38) genotype (P<0.001). GG genotype was significantly higher in keloid patients and increased the risk for keloid development by nearly14 folds (p<0.001, OR (95%CI) =13.81).  CG genotype was significantly observed in keloid patients and increased the risk for keloid development by about 4 times (p=0.010, OR (95%CI) =4.27). G Allele significantly increased the risk for keloid development by about 5 folds (P <0.001 OR =5.11). In conclusion, there was a great association between IL-6 572 gene polymorphism and its serum level in patients with keloid specifically who have family history.

Immunolocalization of MUC1 in chronic plaque psoriasis.

Psoriasis is a chronic skin inflammatory disease with immunological, hyperproliferative and angiogenic dysfunction. MUC1 is a molecular sensor and signal transductor that responds to external stimuli generating cellular responses, which include cell proliferation, growth, differentiation, migration, invasion, survival and secretion of growth factors, and cytokines. The current study aimed at evaluation of the possible role of MUC1 in the pathogenesis of psoriasis through its immunohistochemical localization in involved and uninvolved psoriatic skin compared to normal skin in addition of correlating MUC1 expression with the clinical and pathological parameters of psoriasis. The current study investigated 30 patients with psoriasis and 10 controls. MUC1 was expressed in epidermis in 30% of normal skin compared to 20% of uninvolved epidermis and 63.3% of involved epidermis of psoriatic skin. MUC1 was seen staining endothelial cells of capillaries and inflammatory cells in dermis in 10% of normal skin, 0% of uninvolved psoriasis, and 83.3% of involved psoriasis. Dermal expression of MUC1 in psoriasis was associated with mild to moderate degrees of epidermal acanthosis (p = .027). Intense MUC1 expression by psoriatic epidermis was associated with short disease duration (p = .044). The upregulation of MUC1 in involved psoriatic lesion compared to uninvolved and normal skin may suggest MUC1 role in pathogenesis of psoriasis especially early stages. MUC1 may be responsible for less severity of psoriasis in old aged patients.

Adiponectin serum levels and ADIPOQ (rs2241766) polymorphism in alopecia areata Egyptian patients.

BACKGROUND: Alopecia Areata (AA) is an acquired autoimmune form of non-scarring hair loss. Adiponectin and its gene polymorphism were related to many autoimmune disorders. OBJECTIVE: Assessment of adiponectin serum levels and adiponectin gene (ADIPOQ) (rs2241766) Single Nucleoid Polymorphism (SNP) in AA patients and correlating the results with the disease severity in those patients. METHODS: This study included 75 AA patients and 75 age and gender-matched healthy subjects (controls). The severity of Alopecia Tool (SALT) score assessment to evaluate AA severity was done. Adiponectin serum levels by ELISA and ADIPOQ (rs2241766) SNP using PCR were performed. RESULTS: Adiponectin serum levels were significantly lower in AA patients than controls (p = 0.001). ADIPOQ (rs2241766) TG genotype and G allele were significantly predominant in AA patients increasing its risk by 5 and 4 folds (OR = 5.17, p = 0.001), (OR = 3.82, p = 0.001) respectively. Serum adiponectin levels were negatively correlated with SALT score (r = -0.435, p = 0.001) and associated with alopecia totalis (p = 0.016). ADIPOQ (rs2241766) TG genotype was significantly associated with low serum adiponectin levels and higher SALT score (p = 0.001). STUDY LIMITATIONS: The small sample size. CONCLUSIONS: ADIPOQ (rs2241766) gene polymorphism (TG genotype and G allele) may modulate AA risk and contribute to the development of AA in Egyptian populations. Decreased circulating adiponectin levels may have a dynamic role in AA etiopathogenesis. Adiponectin serum concentration can be considered a severity marker of hair loss in AA.

Serum and Seminal Plasma Levels of Lead and Arsenic in Cigarette Smokers and Their Relation to the Semen Parameters.

Male infertility along with altered semen parameters have been related to smoking. Smoking-related elevations in serum and seminal lead (Pb) and arsenic (As) may play a role in mediating the toxic effects of smoking on seminogram. This research aims to determine whether smoking has any significant impact on Pb and As levels in the seminal plasma and serum, as well as on the various semen parameters, when compared to nonsmokers. In total, 80 adult males were included: 60 smokers and 20 age-matched nonsmokers. Based on the number of cigarettes smoked/day (CPD), the smokers were categorized into mild (1-10), moderate (11-20), and severe (> 20). The analysis of semen was conducted in accordance with the 2010 WHO laboratory manual. Using an atomic absorption spectrophotometer, Pb and As concentrations in the serum and seminal plasma of all groups were determined. Compared to nonsmokers, smokers had a significantly reduced sperm count, motility, and viability, as well as a larger percentage of aberrant forms (P = 0.001, 0.025, 0.034, 0.002 respectively). Smokers had higher Pb concentrations in their serum and seminal fluid than nonsmokers (P = 0.002, 0.001 respectively). Seminal Pb had a significant negative correlation with sperm count (P = 0.004, r = -0.320). Serum Pb levels were found to positively correlate with seminal Pb levels (P 0.001, r = 0.648), and cigarette smokers had substantially greater seminal As levels than nonsmokers (P = 0.024). Sperm viability was strongly inversely related to seminal As (P = 0.042, r = -0.264). Seminal As levels and aberrant sperm shapes were found to be significantly correlated (P = 0.001, r = 0.414). In smokers, a significant positive relationship between seminal As and seminal Pb was observed. Therefore, semen parameters could be adversely affected by smoking through high levels of Pb and As (P = 0.012, r = 0.298).

Human beta-defensin 1 circulating level and gene polymorphism in non-segmental vitiligo Egyptian patients.

BACKGROUND: Vitiligo is an acquired depigmented skin disorder. It has a genetic and autoimmune background. Human beta defensin-1(HBD-1) plus its gene polymorphism were linked to some autoimmune disorders. OBJECTIVE: To elucidate the possible role of HBD-1 in the pathogenesis of non-segmental vitiligo (NSV) through evaluation of HBD-1 serum levels and its single nucleotide polymorphism (SNP) in patients having NSV, in addition, to correlating the results with the extent of vitiligo in those patients. METHODS: A current case-control study included 50 patients having NSV and 50 controls. The authors used Vitiligo Area Scoring Index (VASI) score to assess vitiligo severity and laboratory investigations to assess serum HBD-1 level using ELISA and defensin-beta1 (DEFB1) SNP using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: There were significantly lower HBD-1 serum levels in NSV cases than in controls (p < 0.001). There was a significant predominance of GG DEFB1 genotype and G allele in NSV patients in comparison to controls (p < 0.001). The levels of serum HBD-1 and DEFB1 genotypes were not associated or correlated significantly with any of the personal and clinical parameters of vitiligo patients. STUDY LIMITATION: The small sample size. CONCLUSIONS: DEFB1 gene polymorphism (GG genotype and G allele) may modulate vitiligo risk and contribute to vitiligo development in Egyptian populations. Decreased circulating HBD-1 levels might have an active role in vitiligo etiopathogenesis that could be mediated through its possible anti-inflammatory effects.

Interleukin-17A in Egyptian leprosy patients: a clinical, genetic, and biochemical study.

BACKGROUND: Leprosy represents a long-term communicable disease resulting from Mycobacterium leprae infection. IL-17A is one of the pro-inflammatory cytokines that protects humans against many fungal and bacterial pathogens. OBJECTIVE: To investigate IL-17A (rs2275913) gene polymorphism and its circulating level in leprosy patients, and to correlate the detected results with different clinical aspects of leprosy in the investigated patients. METHODS: 60 patients with leprosy, and 29 age and sex-matched volunteers were investigated for IL-17A serum level and IL-17A single nucleotide polymorphism (SNP) by ELISA and RFLP-PCR respectively. RESULTS: IL-17A serum level was significantly higher in leprosy patients than in controls (p=0.034), and in TL than LL (p=0.017). IL-17A (rs2275913 A/G) G allele and GG genotype were associated significantly with LL (p=0.005and 0.001 respectively). IL-17A (rs2275913 A/G) AG genotype carriers demonstrated the highest IL-17A serum levels; however, its lowest levels were found in IL-17A (rs2275913 A/G) AA genotype carriers (p=0.005). Grade 2 disability (p=0.030) and positive slit skin smear (SSS) (p=0.005) were significantly associated with IL-17A (rs2275913 A/G) GG genotype. STUDY LIMITATIONS: The small number of studied subjects. CONCLUSIONS: IL -17A may have a pivotal role in leprosy pathogenesis. IL-17A (rs2275913) GG genotype plus G allele might be related to the development of LL in the Egyptian population.

The clinical and pathological effectiveness of microneedling and topical 5-fluorouracil in vitiligo treatment: An association with matrix metalloproteinase 2 immunohistochemical expression.

BACKGROUND: The current therapies for vitiligo require long duration with often disappointing outcomes. 5-Fluorouracil (5-FU) is a chemotherapeutic agent approved for topical use in the treatment of several dermatologic conditions. Matrix metalloproteinase 2 (MMP2) is synthesized by keratinocytes during the epidermal remodeling process and has been found to help in melanocyte migration. AIM: To investigate the efficacy and safety of flexible microneedling followed by application of 5-FU in vitiligo treatment and to evaluate the immunohistochemical expression of MMP2 in involved skin in vitiligo patients before and after treatment. METHODS: Twenty patients presented with vitiligo were planned to receive one session every 2 weeks for 12 weeks of microneedling followed by 5-FU application. Clinical response to therapy was evaluated by VASI score. Pre- and post-treatment biopsies were taken from vitiliginous patches for MMP2 immunostaining. RESULTS: Fifteen patients (75%) responded to therapy with observed side effects such as pain, erythema, and hyperpigmentation of margins. The clinical response was more in young patients and those who have short disease duration. MMP2 was significantly increased in post-treatment biopsy compared with the pretreatment one. CONCLUSIONS: 5-Fluorouracil application after microneedling is effective in the treatment of vitiligo with 75% response, 60% patient satisfaction, and tolerable side effects. The improvement in vitiligo patients by microneedling and 5-fluorouracil could be due to upregulation of MMP2 in affected vitiligo specimens.

Immunohistochemical expression of SOX2 in non-melanoma skin cancer.

BACKGROUND: Basal cell carcinoma (BCC) followed by squamous cell carcinoma (SCC) are the most common non-melanoma skin cancer (NMSC). SOX2 is a transcription factor that acts on various phases of embryonic development and its overexpression in many tumors has been reported. AIM: This work aimed to evaluate the possible role of SOX2 in pathogenesis of non-melanoma skin cancer through its immunohistochemical assessment in BCC and SCC compared to normal skin and correlating its expression with the established prognostic factors. METHODS: The investigated cases were 24 BCC, 21 SCC, and 26 normal skin specimens. RESULTS: SOX2 was not expressed in normal skin, but it was upregulated in SCC (85.7%) and BCC (66.7%), with a significant difference between malignant cases and normal skin (p < 0.001). However, SOX2 expression did not differ between SCC and BCC. SOX2 expression was associated with large-sized tumors in all malignant cases (BCC plus SCC) (p = 0.02) and in SCC (p = 0.043) alone together with its liability to be expressed in advanced stage in SCC (p = 0.063). CONCLUSIONS: SOX2 was over-expressed in cutaneous SCC and BCC without a significant difference. SOX2 may enhance progression of NMSC manifested by its association with large tumor size and advanced stage.

Fatty acid-binding protein 4 circulating levels in non-segmental vitiligo.

BACKGROUND: Vitiligo is an acquired and progressive mucocutaneous disease resulting from the loss of active epidermal melanocytes. Metabolic syndrome (MetS) affects about 25% of the world's population and is linked to inflammatory skin diseases including vitiligo. Fatty Acid-Binding Protein 4 (FABP4) is an intracellular lipid chaperone. FABP4 is closely associated with MetS. OBJECTIVES: To evaluate the serum level of FABP4 in vitiligo patients and its relation to MetS in the investigated cases. METHODS: This case control study was conducted on 45 patients having non segmental vitiligo and 45 matched controls. Their lipid profile, blood glucose and serum FABP4 levels were measured. RESULTS: There were significant elevations in FABP4 (p < 0.001), cholesterol (p < 0.001), triglycerides (p = 0.005), and glucose (fasting [p = 0.001] and 2 hours post prandial [p < 0.001]) levels in patients in comparison with controls. MetS was significantly more prevalent among vitiligo patients (p < 0.001) and associated with high FABP4 serum levels (p = 0.037). In vitiligo patients, there were significant positive correlations between FABP4 serum levels and triglycerides (p = 0.047), cholesterol (p = 0.001) and LDL (p = 0.001) levels and negative correlation regarding HDL level (p = 0.009). FABP4 level was a significantly good diagnostic test for early detection of vitiligo (p < 0.001). STUDY LIMITATIONS: The small number of studied subjects. CONCLUSIONS: FABP4 may play an active role in the disease process of vitiligo that could be mediated through associated dyslipidemia and hyperglycemia. FABP4 may be a marker of vitiligo helping in its early diagnosis, but it does not appear to be useful for determining vitiligo severity, activity or associated MetS.

Evaluation of the Langerhans cells role in vitiligo and its relationship to NB-UVB.

BACKGROUND: Langerhans cells (LCs) are antigen-presenting cells that are characterized by CD1a and CD207/langerin expression. The disturbance in the communication network among keratinocytes, melanocytes, and antigen-presenting cells may be involved in vitiligo pathogenesis. AIMS: The current work aims to detect and quantify LCs in involved skin of patients affected by vitiligo before and after treatment with NB-UVB using CD1a immunohistochemistry, in addition to correlate percentage of LCs with the clinicopathological parameters. METHODS: Twenty vitiligo patients and 10 age and sex matched controls were investigated. Patients were received NB-UVB thrice weekly for 12 weeks. RESULTS: There was a significant reduction in LCs percentage in skin affected by vitiligo before treatment in comparison with normal skin. About 65% (13/20) of vitiligo patients responded to NB-UVB, and the liability to respond was correlated with LCs percentage in specimens before treatment. However, there was no statistical difference between specimens before and after treatment regarding LCs percentage. CONCLUSIONS: Reduction in LCs in vitiligo may be a sign of active disease and melanocytes destruction. The percentage of LCs affects response to NB-UVB since higher percentage is associated with greater response to therapy. Therefore, modulation of LCs as a type of immunotherapy could be beneficial in improvement of vitiligo.

Tissue expression of IL-17A and FOXP3 in acne vulgaris patients.

BACKGROUND/OBJECTIVES: CD4+  T helper (Th) cells through its pro-inflammatory cell type, interleukin-17 (IL-17)-generating cells and its anti-inflammatory category forkhead box P3-positive (FOXP3+ ) regulatory T (Treg) cells, play a vital role in the immune balance in inflammatory disorders. Therefore, assessment of both IL-17 and FOXP3 in acne vulgaris (AV), a chronic inflammatory disease of the pilosebaceous unit, could be of value in understanding AV pathogenesis. This study aimed to investigate the immunohistochemical expression of IL-17A and FOXP3 in acne vulgaris lesions versus normal skin. METHODS: Forty-five AV patients and 25 controls were included in this case-control study. Biopsies from participants were analyzed for IL-17A and FOXP3 immunohistochemical profiles using IL-17A and FOXP3 polyclonal antibodies. RESULTS: Compared to controls, AV patients exhibited a significant increase of IL-17A percent of expression in epidermis (P ≤ .001), in lymphocytes in papillary dermis (P ≤ .001), and in perifollicular lymphocytic inflammatory infiltrate in AV lesions. Also, there was a significant elevation in FOXP3 percent of expression in epidermis (P = .049) and in lymphocytes in papillary dermis (P ≤ .027) in acne patients than control. A significant positive correlation between IL-17A expression in papillary lymphocytes and in epidermal keratinocyte was observed (r = .537, P = .001). In acne vulgaris patients, the associations between IL-17A and FOXP3 expressions could not reach level of significance. CONCLUSIONS: There was an up-regulation of IL-17A and FOXP3 in acne vulgaris development, but with independent roles. Moreover, targeting of IL-17A and FOXP3 may open the door for development of new therapeutic agents in acne vulgaris treatment.

The Role of TROP2 in BCC and Cutaneous SCC: A Clinical and Immunohistochemical Study.

BACKGROUND: Nonmelanoma skin cancer (NMSC) mainly includes basal (BCC) and squamous (SCC) cell carcinoma. Trophoblast cell-surface antigen2 (TROP2), a cell-signal transduction, is one of the tumor-related calcium signal transducer gene family. TROP2 was highly expressed in many cancers, however, its role in BCC and SCC has not yet been studied. OBJECTIVE: To investigate TROP2 immunohistochemical expression in BCC and SCC (lesional and peri-lesional) skin compared to controls and correlates its expression with the clinicopathologic parameters of the studied cases. METHODS: This case-control study included 17 BCC and 15 SCC patients as well as 12 age and sex matched controls. History and clinical examination were completed. Histological examination of skin biopsies was done together with TROP2 immune-staining. RESULTS: In the studied BCC and SCC cases, there was a significant stepwise up-regulation of TROP2 H score from control to peri-lesional, ended by lesional epidermis in one hand (p=0.003 for BCC and p<0.001 for SCC) and tumor island in another hand (p=0.001 for BCC and p=0.003 for SCC). TROP2 expression in both BCC and SCC tumor tissues was not affected by any of the studied clinicopathological parameters of the investigated cases. CONCLUSION: TROP2 could have an important role in BCC and SCC pathogenesis. TROP2 targeting may have appraising effect in clinical application in BCC and SCC management.

Tumour-infiltrating Langerhans cells in non-melanoma skin cancer, a clinical and immunohistochemical study.

Non-melanoma skin cancer, including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) represents 78.5% of all skin malignant tumours in Egypt. Dendritic cells can be found in almost all human tumours, they play an important role in antitumour immunity. The aim of the present study was to evaluate the percentage of Langerhans cells using CD1a in non-melanoma skin cancer, including BCC and SCC and to correlate this percentage with their clinicopathological features. The current study was performed on surgically excised specimens of 41 patients presented with non-melanoma skin cancer (26 BCC and 15 SCC) and 16 healthy volunteer control subjects. The mean and median percentage of Langerhans cells were higher in normal epidermis of control compared to malignant tumour tissue (p < 0.0001) and adjacent epidermis overlying malignant tumour tissue (p = 0.007). Langerhans cells were significantly seen in BCC cases more than SCC (p = 0.035) and they were seen in facial lesions more than those arising from other sites (p = 0.007). The reduction of Langerhans cells is a way for non-melanoma skin cancer to develop and progress. Marked reduction of Langerhans cells in SCC compared to BCC could refer to their role as a barrier against metastasis.

Role of Galectin-9 in Atopic Dermatitis - Is It Mediated Through E Selectin? A Clinical and Immunohistochemical Study.

BACKGROUND: Atopic dermatitis (AD) is a recognized T helper (Th)2, allergic, skin disease. Galectin-9 (gal-9) is a member of galectin family. It alters T-cell balance resulting in Th2 polarization. These Th2 cells yield various cytokines that may influence E selectin expression. Therefore, we hypothesized that gal-9 may have an active role in AD and this role could be mediated through E selectin. OBJECTIVE: To assess this hypothesis, immunohistochemical expression of gal-9 and E selectin was investigated in skin lesions, from atopic dermatitis patients, and compared. METHODS: Twenty-two atopic dermatitis patients and ten controls were included in this case-control study. SCORAD score was used to evaluate atopic dermatitis severity. Biopsies from skin lesions of AD patients and matched sites of controls were taken and stained immunohistochemically by gal-9 and E selectin polyclonal antibodies. RESULTS: Compared to controls, atopic dermatitis patients exhibited a significant increased gal-9 H score, percent of expression, cellular localization (P˂0.001) and intensity (P=0.04) as well as dermal cellular infiltrate (P˂0.001). Also, there were significant elevations in E selectin H score (P=0.002), percent of expression (P=0.001) and cellular localization (P<0.001) as well as dermal inflammatory infiltrates in AD cases than controls. In AD, 20 cases showed co expression of both gal-9 and E selectin in the epidermis with insignificant correlation between their H scores. STUDY LIMITATIONS: This study only included a small number of studied subjects. CONCLUSION: Galectin-9 and E selectin participates independently in atopic dermatitis pathogenesis, that may help in development of new therapeutic agents in atopic dermatitis management program.

Relationship Between sCD163 and mCD163 and Their Implication in the Detection and Typing of Leprosy.

BACKGROUND: Leprosy is a chronic contagious disease caused by Mycobacterium lepraea. CD163 is a monocyte trans-membrane glycoprotein receptor (mCD163) that sheds from the cell surface and circulates as a soluble (serum) form (sCD163). Changes in the mCD163 and sCD163 levels could mirror the categorization of inflammatory procedure, demonstrating a possible use of CD163 as a diagnostic indicator of inflammation. OBJECTIVE: To investigate the possible role of CD163 (sCD163 and mCD163) in leprosy pathogenesis and to assess whether CD163 is a helpful inflammatory marker of leprosy development and typing. PATIENTS AND METHODS: This case control study included 70 leprosy patients and 30 healthy controls. Leprosy patients were classified according to the Madrid criteria (1953) into: tuberculoid leprosy (TT), border-line leprosy (BL), and lepromatous leprosy (LL). For all participants, complete blood count (CBC), serum CD163 using ELISA and monocytes positive for CD163 using flow cytometry were done. RESULTS: Leprosy patients had significantly low WBCs and platelet counts (p<0.001) and had significantly higher sCD163 (p=0.025) and mCD163 (p=0.042) that were highest in LL followed by BL, then TT patients (p<0.001). There was a significant positive correlation between mCD163 and sCD163 levels in leprosy patients (r=0.896, p<0.001). ROC analysis revealed a significant role of serum sCD163 and of mCD163 positive monocytes in the detection (p<0.001) and typing of leprosy (p=0.002 and p<0.001, respectively). CONCLUSION: Both sCD163 and mCD163 positive monocytes may have an active role in leprosy pathogenesis. They could be potential biomarkers for leprosy detection and typing.

Immunohistochemical study of janus kinase 1/signal transducer and activator of transcription 3 in psoriasis vulgaris.

Background: Human JAKs are responsible for generating docking sites for human SSTAT phosphorylation. The role of JAKs in psoriasis pathogenesis has not been clearly explained. Aim: To investigate the role of JAK1 in psoriasis pathogenesis and to assess if this role is mediated through STAT3 or not, through evaluation of their immunohistochemical expression in the skin of psoriatic patients. Methods: This case-control study was carried out on 26 patients presenting with psoriasis vulgaris versus 26 age- and sex-matched apparently healthy volunteers. Psoriasis Area and Severity Index (PASI) scores were used to evaluate psoriasis severity. From all controls and cases (lesional and perilesional), skin biopsies were taken for histopathological and immunohistochemical JAK1 and STAT3 evaluation. Results: There was significant stepwise upregulation of JAK1 from controls to perilesional to lesional psoriatic skin of the patient group in both epidermis and dermis (P≤0.001 for both). Dermal JAK1 H-score was significantly associated with psoriasis severity (P=0.01). STAT3 was significantly overexpressed in lesional psoriatic skin over nonlesional skin (P<0.001). There were significant positive correlations between lesional H-scores for STAT3 and Psoriasis Area and Severity Index scores in epidermis (r=0.63, P<0.001), and in dermis (r=0.47, P=0.04). There was a significant positive correlation between JAK1 and STAT3 expression in epidermal lesional psoriatic skin (r=0.44, P=0.03). Conclusion: JAK1 has a proinflammatory effect in psoriasis pathogenesis, which could be mediated through increasing STAT3 expression in psoriasis. JAK1 and STAT3 tissue expression could be markers of psoriasis severity. JAK1 may be used as a target for immunotherapy in psoriasis-management programs.

Second to fourth digit ratio in female patients with acne vulgaris: Could it be a predictor of androgen receptor status?

BACKGROUND: Second to fourth digit (2D:4D) ratio is the ratio of index to ring fingers length. It reflects prenatal androgen exposure and sensitivity. Androgens are important in the pathogenesis of acne vulgaris, This ratio may therefore be of significance in determining the expression of androgen receptors. AIM: To investigate the relationship between second to fourth digit ratio and androgen receptor expression in female patients with acne vulgaris and to assess its association with clinical aspects of acne vulgaris. METHODS: Females patients (n = 352) with different degrees of acne vulgaris severity and 168 age-matched females were enrolled. Right, left and total second to fourth digit ratios were calculated. Biopsies from all participants were processed for androgen receptor expression by immunohistochemical method. RESULTS: Right, left and total second to fourth digit ratios were significantly lower in acne vulgaris patients than controls (P < 0.001 for all), and each of them had a significant negative correlation with duration of acne vulgaris (P < 0.001; P = 0.013; P < 0.001, respectively). Androgen receptors were detected in epidermal keratinocytes, hair follicles, sebaceous glands and fibroblasts. Right second to fourth digit ratio showed a negative correlation with androgen receptor H score of keratinocytes (r = -0.28;P = 0.02), hair follicles (r = -0.22; P = 0.05) and fibroblasts (r= -0.37;P = 0.001), while left second to fourth digit ratio demonstrated negative correlation with androgen receptor H score of sebocytes (r = -0.397; P < 0.000) only. LIMITATIONS: Lack of follow-up and absence of male participants were the main limitations of this study. CONCLUSION: A masculine second to fourth digit ratio in female patients could anticipate acne vulgaris development, its duration and severity. Moreover, this ratio is associated with an upregulation of cutaneous androgen receptors. Taken together, second to fourth digit ratio could help in designing plans for treatment of acne vulgaris.