Tissue and circulating levels of IL-17A and FoxP3+ in patients with scabies: Correlation with clinical features.

The scabies mite is known to induce a complicated immune response that involves both innate and long-term adaptive immunity. Many immune effectors and pathways are involved. Th17/Treg balance can influence the complex immune response to scabies. The immunological effectors including IL-17A, as a pro-inflammatory cytokine, and Treg cells, anti-inflammatory regulatory T cells, are essential for preserving cutaneous immunological homeostasis. So, evaluating these immune effectors may help in comprehending the pathophysiology of scabies and facilitate the development of new treatment approaches. This study examined the expression of IL-17A and FoxP3+ in the skin and serum of 50 scabies patients and 25 healthy controls. An assessment of their correlation with clinical features was performed. Regarding tissue response, scabietic patients exhibited a significant increase in IL-17A and FoxP3+ expression in their epidermis and dermis compared to controls (P<0.001), but the correlation between these factors was not significant in either area (P>0.05). Also, patients showed a significant increase in serum IL-17A levels compared to controls (P<0.001), with a significant association between serum IL-17A levels and lesion severity, but no significant correlation was observed between skin and serum responses (P>0.05). In conclusion, there was increased expression of both IL-17A and FoxP3+, with FoxP3+ being significantly more abundant than IL-17A in the skin of scabies patients. Skin FoxP3+ up-regulation has been linked to the severity of the condition.

Reappraisal of psoriasis pathogenesis: the role of TEAD4 expression in keratinocytes.

BACKGROUND: Psoriasis is an immune-mediated inflammatory skin disorder with a multifaceted pathogenesis. Immune dysregulation and immune cell dysfunction are among the mechanisms involved. TEA domain family member 4 (TEAD4) is suggested to play a role in psoriasis development. TEAD4 expression in keratinocytes may have a chemotactic effect and could disturb the function of FOXP3-positive T lymphocytes. This study aimed to evaluate the expressions of TEAD4 and FOXP3 in lesional, nonlesional psoriatic, and healthy skin and assess the clinical impact of their expression. METHODS: This case-control study included 32 cases with psoriasis vulgaris and 32 control groups. Hematoxylin and eosin-stained slides were examined to evaluate the histopathological findings. Moreover, other sections were immunohistochemically stained with FOXP3 and TEAD4. RESULTS: FOXP3 was expressed in inflammatory cells in 56.5, 37.5, and 12.5% of lesional, nonlesional, and healthy skin, whereas it was entirely negative in the keratinocytes. TEAD4 was expressed in keratinocytes in 93.7 and 46.9% of lesional and nonlesional skin, while negative in healthy skin. Significant differences were observed between their lesional, nonlesional, and healthy skin expressions. Furthermore, FOXP3 expression in lesional skin was significantly associated with early onset (P = 0.016), low PASI score (P = 0.002), mild psoriasis (P = 0.007), and axial affection (P = 0.022), while TEAD4 expression was associated with progressive course (P = 0.032), high PASI score (P = 0.002), severe psoriasis (P = 0.001), severe inflammation (P = 0.001), and progressive course (P = 0.017). CONCLUSION: TEAD4 expression was higher in lesional than nonlesional skin and absent in healthy skin, suggesting a role in psoriasis development. TEAD4 expression was also associated with severe and progressive psoriasis. This may be mediated by the downregulation of FOXP3 and dysfunction of Treg cells. TEAD4 could serve as a promising therapeutic target in psoriasis.

Uncoupling protein 2 and dynamin-related protein 1 mRNA expressions as genetic markers for plaque psoriasis.

BACKGROUND: Psoriasis is a long-lasting, inflammatory disease of the skin with not fully understood pathogenesis. Uncoupling protein 2 (UCP2) and dynamin-related protein 1 (Drp1) are the main mitochondrial regulatory proteins implicated in various inflammatory conditions. This work aimed to evaluate the role of UCP2 and Drp1 messenger RNA (mRNA) expressions in diagnosing plaque psoriasis and to correlate their expression levels with the available clinical data. METHODS: Total number of 210 subjects (105 plaque psoriasis patients and 105 healthy volunteers) was enrolled in the current study. Plasma UCP2 and Drp1 mRNA relative expressions were studied by real-time polymerase chain reaction technique. RESULTS: A significant statistical decrease in the expression levels of the mitochondrial regulatory proteins UCP2 and Drp1 mRNA in plasma of patient group in comparison to control subjects (P < 0.001). UCP2 mRNA expression was significantly correlated with the onset of disease and scalp affection (P < 0.05). The receiver operating characteristic (ROC) curve was the test used for verification of the accuracy of UCP2 and Drp1 mRNA expressions in identifying cases from healthy control subjects; UCP2 mRNA expression had a greater percent of accuracy (94%), sensitivity (97%), and specificity (87%) than Drp1 mRNA expression. CONCLUSIONS: Although UCP2 and Drp1 mRNA are downregulated in plasma of psoriatic patients, UCP2 could serve better as a promising marker for plaque psoriasis. Despite developments in the treatment of psoriasis, these results provide new insights in disease pathogenesis suggesting UCP2 may be a good target for treatment.

Serum resistin levels and resistin gene polymorphism in patients with acne vulgaris: does it correlate with disease severity?

BACKGROUND: Acne vulgaris is a disease that inflames the sebaceous gland with multiple etiologies. Many proinflammatory adipokines contribute to this pathogenesis. Resistin is a proinflammatory mediator that activates kappa B, a nuclear factor, and c-Jun N-terminal kinases pathways inducing toll-like receptor-2, interleukin-1, 6, and tumor necrosis factor alpha. Resistin gene affects the promoter and intron regions' polymorphisms' expression levels. We aimed to study the association of resistin gene polymorphisms (RETN -420 C/G) and the development of acne vulgaris and whether it is associated with serum resistin levels and disease severity. SUBJECTS AND METHODS: Resistin (RETN) gene (rs1862513) genotypes were identified using restriction fragment length polymorphism (RFLP), and serum resistin presence was assessed by enzyme-linked immunosorbent assay in 40 patients with acne vulgaris and 40 age- and sex-matched healthy controls as a cross-reference. Patients were divided into mild, moderate, and severe groups. Global Acne Grading System (GAGS) was used to assess the severity of acne vulgaris. RESULTS: CG and GG genotypes were present in cases (P = 0.006) odds ratio (OR)1 = 4.43; 95% confidence interval (CI) (1.53, 12.7) and OR2 = 5.47; 95% CI (0.99, 30.1); G-allele statistically dominated in the patient group where P = 0.001 and OR = 3.57; 95% CI (1.63, 7.80). A positive significant relationship between RETN genotypes and serum resistin levels and GAGS score was present. CONCLUSION: RETN genes rs1862513 GG and G allele are correlated to acne vulgaris development and severity in a sample of the Egyptian population. This study comprised a small sample size. The cases may not accurately represent the general population; only one clinic was enrolled in the study.

Valosin-containing Protein in Psoriasis: A Clinical and Immunohistochemical Study.

Psoriasis is a chronic immune-mediated inflammatory skin disease, affects about 2% to 3% of the world population. Valosin-containing protein (VCP) is one of the newly discovered markers that is highly expressed in neoplasms and hyperproliferative lesions. This work aimed to study the role of VCP in psoriasis vulgaris by immunohistochemical study and correlate its expression with the available clinicopathologic data. This prospective case-control study was conducted on 25 patients with psoriasis vulgaris and 25 age-matched and sex-matched healthy individuals as a control group. Skin biopsies were taken under local anesthesia from cases and controls. VCP immunoreactivity showed that epidermal VCP expression had a significant stepwise increase (P=0.002) from control to lesional psoriatic sections. Epidermal VCP H-score was significantly associated with the progressive course (P=0.037). Similarly, VCP in the dermis showed a significant expression in lesional psoriatic skin (P≤0.001). Higher VCP in the dermis in cases with a history of joint affection (P<0.05) was detected. We concluded that VCP is a promising marker for follow-up and monitoring of psoriatic patients and may play a role as a therapeutic target.

Genetic polymorphism of liver X receptor gene in vitiligo: Does it have an association?

BACKGROUND: Vitiligo is an acquired depigmentation of the skin and the mucous membranes, exhibited as white macules and patches due to selective loss of melanocytes. Etiological theories of vitiligo include genetic, immunological, neurohormonal, cytotoxic, biochemical, oxidative stress, and newer theories of melanocytorrhagy and diminished melanocytes survival. It has been revealed that liver X receptor alpha gene is expressed in skin tissue such as sebaceous glands, hair follicle, keratinocytes, and fibroblasts and is linked to various skin disorders as acne vulgaris and psoriasis. AIM OF THE STUDY: To evaluate the association between liver X receptor-α gene polymorphism (rs11039155 and rs2279238) and vitiligo and whether they are related to disease activity and severity or not. SUBJECTS AND METHODS: 50 vitiligo patients and 20 age- and sex-matched apparently healthy controls were enrolled. All the included subjects were genotyped using polymerase chain reaction-restriction fragment length polymorphism analysis technique for (-6G/A) and (+1257C/T) SNPs. RESULTS: Significant statistical difference between cases and controls regarding genotype and allele frequencies for -6G/A polymorphism with predominance of AA genotype (OR: 5.1, 95% CI: 1.6-15.9) and A allele (OR: 5.3, 95% CI: 1.6-15.9) in cases and also for +1257C/T polymorphism with predominance of TT genotype OR: 9.2 (95% CI: 1.4-82.9) and T allele OR: 3.4 (95% CI: 1.4-8.1) in vitiligo cases. No significant relationship between -6G/A genotypes nor +1257C/T genotypes and disease activity and severity. CONCLUSION: The study showed significant association between Liver X receptor gene polymorphisms (-6G/A, +1257 C/T) and development of vitiligo in Egyptian patients. However, it failed to show any relation with disease activity nor severity.

ESR1 gene polymorphism (rs827421) as a potential genetic marker for constitutional delay of growth and puberty in Egyptian adolescents.

Constitutional delay of growth and puberty (CDGP) is a variant of normal pubertal timing and progress. It is the most common form of delayed puberty in both genders. The genetic director of CDGP is ill-understood despite the positive family history result noted in those patients. The current study aimed at assessing the role of estrogen receptor 1 (ESR1) gene variant (rs827421) in Egyptian adolescents with CDGP. A cross-sectional study with follow-up part was carried out on 6760 children aged 4 to15 years. The study focused generally on children aged 13-15 years in order to evaluate the prevalence of delayed puberty in relation to all ages in general and to their peers in specific. Assessment of serum TSH, FSH, and LH was conducted on all participants, along with the measurement of serum-free testosterone for males and estradiol for females. Genotyping of ESR1 (rs827421) was done to all subjects through the use of TaqMan discrimination assay by real-time PCR. ESR1 (rs827421) GG genotype and G allele were significantly dominant among CDGP adolescents in comparison with controls (OR = 25.67 and 6.90). As regards follow-up of testicular size, AA genotype was significantly associated with increased size in the right and left testis compared to other genotypes (P = 0.021 and 0.006, respectively). Moreover, AA genotype showed significantly higher Tanner stage in both males and females in comparison with other genotypes. Serum estradiol level was significantly higher in AA genotype group than other genotypes groups. ESR1 gene polymorphism can be considered a potential genetic marker for CDGP in both sexes in a sample of Egyptian adolescents.

Resistin adipokin in atopic dermatitis patients: A clinical, biochemical, and genetic study.

BACKGROUND/OBJECTIVES: Atopic dermatitis (AD) is an inflammatory chronic skin disorder. The etiology of AD is not fully understood. Therefore, we aimed by this study to shed light on the potential role of resistin in an etiopathogenesis of AD through investigation of resistin rs3745367 single nucleotide polymorphism (SNP) and resistin serum levels, and their relation to leukocytic count in a sample of Egyptian patients having atopic dermatitis. METHODS: This case-control study included 45 patients having AD and 40 controls. SCORAD index was assessed to evaluate the severity of AD. CBC, ELISA, and PCR-RFLP were performed to detect leukocytic count, resistin serum level, and resistin rs3745367 SNP, respectively. RESULTS: Atopic dermatitis patients had significant low serum resistin concentrations (P = .036) and a significantly high frequency of leukocytosis (P = .003). Low resistin serum levels were significantly related to AD disease severity (P < .001) and the presence of leukocytosis (P < .001). Resistin rs3745367 GG genotype (P = .030), as well as its G allele (P = .019), was expressively associated with AD development, and both increased the risk of AD by 3- and 2-fold, respectively. Resistin rs3745367 GG genotype was significantly linked to low resistin serum levels (P < .001), AD-positive family history (P = .015), and the presence of leukocytosis (P < .001). CONCLUSIONS: Resistin rs3745367 gene polymorphism may contribute to the development of AD. Resistin may have an immune-modulating active character in the AD etiopathogenesis that could be mediated through its anti-inflammatory effect. From this piece of work, we may suggest resistin as a new therapy to mitigate the pro-inflammatory environment found in AD.

Thyroid disorders associated with alopecia areata in egyptian patients.

CONTEXT: Alopecia areata (AA) is a common form of localized, non-scarring hair loss. The etiopathogenesis of the disease is still unclear, but the role of autoimmunity is strongly suggested. AA is commonly associated with various autoimmune disorders; the most frequent among them is autoimmune thyroid disorders. AIM: To determine whether AA is associated with thyroid autoimmunity or thyroid function abnormalities in Egyptian patients. MATERIALS AND METHODS: Fifty subjects with AA (37 males and 13 females) without clinical evidence of thyroid disorders were selected from Dermatology Outpatient Clinic, Menoufiya University Hospital, Menoufiya Governorate, Egypt, during the period from June 2009 to February 2010. They were divided into 3 groups according to severity of AA. Fifty age and sex-matched healthy volunteers (35 males and 15 females) were selected as a control group. Every case and control were subjected to history taking, complete general and dermatological examination. Venous blood samples were taken from cases and controls after taking their consents for measurement of thyroid stimulating hormone (TSH), free T3, freeT4 and detection of Anti-thyroglobulin Antibody (Tg-Ab) and Anti-thyroid Peroxidase Antibody (TPO-Ab). RESULTS: Subclinical hypothyroidism was detected in 16% of cases. There were statistically significant differences between cases and controls regarding levels of TSH, free T3 and free T4. There were significant differences between cases and controls regarding the presence of Tg-Ab and TPO-Ab. CONCLUSIONS: Every patient with AA should be screened for thyroid functions and presence of thyroid autoantibodies even in absence of clinical manifestations suggestive of thyroid affection.