Association between IL-17F, IL-17RA Gene Polymorphisms and Response to Biological Drugs in Psoriasis and Beyond.

Psoriasis is a systemic inflammatory disease that associates with multiple comorbidities. It involves complex interactions between environmental factors and polygenic predisposition. The IL-17 family is one of the main actors in the pathogenesis of psoriasis. Secondary nonresponse is common, especially during the long-term use of TNF-α inhibitors, but it is not uncommon even for newer biologics, such as IL-17 inhibitors. Identification of clinically useful biomarkers of treatment efficacy and safety would enable optimal treatment selection, improve patient quality of life and outcome, and reduce healthcare costs. To our knowledge, this is the first study to evaluate the relationship between genetic polymorphism of IL-17F (rs763780) and IL-17RA (rs4819554) and response to biological treatment and other clinical data in bio-naive and secondary non-responders psoriasis patients in Romania and Southeastern Europe. We performed a prospective, longitudinal, analytical cohort study of 81 patients diagnosed with moderate-to-severe chronic plaque psoriasis who received biological treatments for the first time. Of the 79 patients treated with TNF-α inhibitors, 44 experienced secondary nonresponse. All patients were genotyped for the two SNPs in IL-17F and IL-17RA genes. The rs763780 polymorphism in the IL-17F gene could be an attractive candidate biomarker for predicting which patients will respond to anti-TNF-α therapies. Another emergent association of rs4819554 in IL-17RA with the risk of nail psoriasis and a higher BMI in moderate-to-severe plaque psoriasis patients is described.

Influence of vitamin D receptor polymorphism rs2228570 on pathological scarring.

The physiological process of scarring is a common denominator of interest in a plethora of medical specialties. The molecular basis whereby this process results in pathological scarring for some individuals is poorly understood at present, with clues pointing towards individual predisposition for pathological scarring. Vitamin D and its subsequent pathway plays a key role in skin metabolism and homeostasis, with alterations in the level of vitamin D receptor (VDR) seen within pathological scars. The present study investigated the role of the rs2228570 polymorphism of VDR with regards to scar formation and evolution in a group of 71 female patients recovering from Caesarian section. Blood samples were taken at the time of surgery, and the follow-up was collected remotely at 3 and 6 months after surgery. The rs2228570 polymorphism was investigated using an RFLP-PCR protocol. The results demonstrated that the CC genotype, in combination with the Patient Observer Scar Assessment Scale (POSAS) and SCAR scores are associated with pathological scarring, with more studies being necessary to draw a firm conclusion.

Role of hTERT rs2736100 in pathological scarring.

Hypertrophic and atrophic scars are the effect of a dysregulated wound-healing process in genetically predisposed individuals. The genetic predisposition has acquired significant attention due to the diverse phenotype of pathological scarring in individuals with a positive personal and family history. Recent studies have identified telomere shortening and decreased hTERT activity in pathological scarring, proposing the rs2736100 variant of human telomerase reverse transcriptase (hTERT) gene as a valuable variant gene candidate. We examined the scarring process in 71 female patients who had undergone Caesarean section and developed hypertrophic and atrophic scars with the objective to investigate the role of single nucleotide polymorphism (SNP) rs2736100 in pathological scarring. Genotyping was performed using RT-PCR and follow-up included the Patient Observer Scar Assessment Scale (POSAS) and SCAR scales. Comparative analysis for mean POSAS value between the check-ups at 3 and 6 months revealed a statistical decreased difference of 1.71 points [95% confidence interval (CI), 0.4-2.89; P=0.01], while SCAR highlighted a decreased difference of 0.670 (95% CI, -0.04-1.38; P=0.055). The C variant allele revealed a borderline statistical value for the risk of developing pathological scarring (OR=1.44; 95% CI, 0.876-1.332: P=0.066). In our study a pre-conceptional body mass index (BMI) >25 kg/m2 was statistically associated with pathological scarring. The Fitzpatrick type 4 phototype displayed an increased frequency for the heterozygous genotype in the current study, and it was demonstrated that dark skin tone was associated with abnormal scar formation. Our study investigated the role of hTERT gene variant rs2736100 in hypertrophic and atrophic scarring in a Caucasian population group. We report a borderline statistically significant value for the variant C allele of hTERT SNP for the risk of developing pathological scarring in female patients that had undergone Caesarean section.

Involvement of COL5A2 and TGF-ß1 in pathological scarring.

Dysregulation in the cutaneous wound-healing process is a consequence of alterations in the efficiency and activity of the various components involved in the healing process. This dysregulation may result in various clinical appearances of a lesion, such as skin ulcers, keloids, hypertrophic and atrophic scars. The collagen type V alpha 2 (COL5A2) gene provides a template for a component of type V collagen, found primarily within the skin basement membrane. Transforming growth factor (TGF)-ß is involved in inflammation, angiogenesis, proliferation of fibroblasts, collagen synthesis and extracellular matrix remodeling. Hypertrophic scar fibroblasts possess a disrupted expression pattern of the TGF-ß signaling compared to normal healing, while an increased TGF-ß signaling reduces the epidermal proliferation rate, triggering atrophic scarring. In the present study, 71 female patients who had undergone planned Caesarean section, without postoperative complications, were examined. These patients were clinically and molecularly evaluated after developing scars in order to determine the role of TGF-ß1 (rs201700967 and rs200230083) and COL5A2 (rs369072636) in pathological scarring. Clinical scar evaluation was carried out using SCAR and POSAS scales and genotyping was performed by RT-PCR. No statistical differences were found between the subgroups regarding the genotype and the pathological scarring, since all the patients included were wild-type allele carriers. Further investigations and a more representative study group may highlight the involvement of COL5A2 and TGF-ß1 single nucleotide variants in pathological scarring.

High-frequency ultrasonography of psoriatic skin: A non-invasive technique in the evaluation of the entire skin of patients with psoriasis: A pilot study.

Psoriasis is a chronic, systemic, inflammatory disorder which accelerates the life process of skin cells, based on a genetically induced deviant immune response. High-frequency ultrasonography (HF-USG) is a painless, non-invasive imaging technique that can be performed and repeated whenever the need arises. We evaluated lesional and non-lesional skin of psoriatic patients with the use of HF-USG, focusing on the immune-induced inflammation and skin thickness. Previous studies suggested that HF-USG, being a non-invasive technique, is useful as an aid to clinical evaluation of the severity of psoriatic plaques. Our goal was to determine whether the skin of psoriatic patients is influenced by the background or habits of the patients. The study included a total of 27 patients affected by psoriasis vulgaris. The thickness of the epidermis and dermis and the skin echogenicity were documented for the active plaques, as well as for the non-affected skin of all the patients included in the study, using a high-frequency ultrasonographic system. The patient's local background, sex, family history of psoriasis, smoking habits and sun exposure were analyzed. HF-USG of the psoriatic plaques exposes a three-band structure that is easily distinguished from the surrounding unaffected skin, due to a hypoechoic band in the upper dermis. Although not specific for psoriasis, it is a strong marker of inflammation. The obtained results confirm that, indeed, skin thickness is greater in lesional skin compared to non-lesional skin, by a mean of 1,180 µm (±340 µm). We consider that skin HF-USG should be used as a quantitative method in the clinical evaluation of the patients with psoriasis and may help as an objective means of assessing inflammation in lesional skin.

The Role Of Adiponectin, TNF-α And Glutathione In The Pathogenesis And Evolution Of Type 1 Diabetes.

INTRODUCTION: Type 1 diabetes (T1DM) is a chronic autoimmune or idiopathic condition, featuring complex and unique interactions between proteins and enzyme systems. The purpose of the present study is to investigate the role of AdipoQ +276G>T, TNF-α-308G>A, GSTT1/GSTM1 polymorphic variants in the development of T1DM. MATERIALS AND METHODS: The study is designed as a cross-sectional study, involving 72 diabetic cases and 90 controls. Genotyping was carried out according to specific protocols for the above-mentioned polymorphic variants. RESULTS: The G allele of AdipoQ was associated with the development of type 1 diabetes (OR 0.577, CI95% 0.336-0.802, p=0.001), similar to the GG and GA genotypes (OR 0.405, CI95% 0.156-0.654, p=0.001 and OR 0.623, CI95% 0.401-0.855, p=0.004). The G allele of TNF-α was marginally associated with the development of type 1 diabetes (OR 0.789, CI95% 0.579-0.956, p=0.005). The presence of the T1 genotype was a strong predictor for type 1 diabetes (OR 3.4, CI95% 1.433-6.243, p<0.001). CONCLUSION: The results of our study suggest that G alleles of AdipoQ and TNFα act as a protective factor in T1DM, while the T1 allele for GST could be considered a risk factor for the development of Type 1 diabetes in our study group.