Chitinase-3-like Protein 1 (YKL-40): A New Biomarker of Inflammation in Pyoderma Gangrenosum.

Pyoderma gangrenosum (PG) is a rare, neutrophilic dermatosis with unclear aetiopathology, considered as an autoinflammatory disease, associated with other immune-mediated disorders. Chitinase-3-like protein 1 (YKL-40) is an inflammatory biomarker secreted by a wide variety of cells, including neutrophils. To evaluate YKL-40 serum level in relation to clinicopathological data, 48 patients with PG and 40 healthy controls were enrolled in the study. Skin lesions were measured to calculate the affected area. Inflammatory parameters (C-reactive protein, white blood cell count with neutrophils) were determined from blood samples. YKL-40 and IL-6 levels were measured in serum by enzyme-linked immunosorbent assay. YKL-40 serum level was significantly higher in patients with PG than in controls (58.4 vs 36.4 ng/ml, respectively; p < 0.00001). The positive correlation between YKL-40 level and IL-6 level was observed (r=0.48, p = 0.0006) along with a trend towards significance of relationship between YKL-40 level and C-reactive protein (r=0.28, p = 0.052). YKL-40 can be considered a valuable biomarker of inflammation in PG.

Serum Concentration and Skin Expression of S100A7 (Psoriasin) in Patients Suffering from Hidradenitis Suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease. An important role of innate immune dysregulation in the pathogenesis of HS has been highlighted. S100A7 (psoriasin) is an innate, antimicrobial protein that exerts proinflammatory and chemotactic action. OBJECTIVES: The objective of the study was to investigate serum concentrations of S100A7 in individuals with HS as compared to healthy controls. Further, we evaluated the expression of S100A7 in lesional HS skin as compared to perilesional (clinically uninvolved) HS skin and normal skin. METHODS: Serum concentrations of S100A7 were evaluated with a commercially available ELISA kit. The expression of S100A7 in the skin was assessed using qRT-PCR and immunofluorescence staining. RESULTS: We found increased expression of S100A7 in lesional HS skin as compared to perilesional HS skin (p = 0.0017). The expression of S100A7 in lesional HS skin was positively associated with serum C-reactive protein concentration and the severity of disease according to Hurley staging. The serum concentration of S100A7 in individuals with HS was decreased as compared to healthy controls and patients with psoriasis. CONCLUSIONS: Upregulated in lesional HS skin, S100A7 may enhance the inflammatory process and contribute to the HS pathogenesis.

Comparison of serum concentrations of interleukins 10, 12, 17 and 35 between patients with alopecia areata and controls.

INTRODUCTION: Alopecia areata (AA) is one of the most common causes of non-scarring hair loss in adults and children with unknown etiopathogenesis, however immunological factors play an important role. AIM: To evaluate the concentration of interleukin (IL) 10 (IL-10), IL-12, IL-17 and IL-35 in the blood serum of patients with AA. MATERIAL AND METHODS: AA study group consisted of 118 patients. The control group consisted of 54 healthy individuals. The severity of the disease was assessed by SALT score. In the study group, the percentage of hair loss averaged 49.6% ±36.3%. The concentration of IL-10, IL-12, IL-17 and IL-35 in the serum was assessed by the enzyme-linked immunosorbent assays (ELISA). RESULTS: In patients with AA, the level of IL-12 and IL-17 was significantly higher than in the control group (p > 0.05). The level of IL-10 in patients was slightly higher, whereas the level of IL-35 was slightly lower, compared to the control group, but those differences were not statistically significant. Furthermore, in patients with more severe disease the IL-12 level was significantly higher as compared to patients with the less severe AA (p < 0.05). CONCLUSIONS: The etiopathogenesis of AA is complex, however Th1 and Th17 lymphocytes and their increased activity are undoubtedly significant contributors in this process. Disorders of immunological processes in AA require further research in order to understand the underlying pathomechanisms of the disease and to provide potential therapeutic strategies.

Chitinase-3-like protein 1 (YKL-40) is a biomarker of severity of joint involvement in psoriatic arthritis.

INTRODUCTION: Psoriasis is an inflammatory disease of a complex pathogenesis and arthritis is one of its most common complications. The biological role of chitinase-3-like protein 1 remains unknown. It is suggested that this protein takes part in processes such as proliferation, inflammation and tissue remodelling. AIM: To determine whether YKL-40 can be a useful biomarker in psoriatic arthritis. MATERIAL AND METHODS: The study was performed on 42 patients with psoriatic arthritis: 28 men and 14 women, aged from 24 to 71 years. All patients met the diagnostic criteria (CASPAR) for psoriatic arthritis. The severity of psoriatic arthritis was assessed using 28-joint Disease Activity Score with CRP. The assessment of skin lesions was performed by Psoriasis Area and Severity Index (PASI) and, additionally, the Body Surface Area (BSA) was calculated. Blood samples were taken to measure the serum concentration of YKL-40, as well as C-reactive protein, erythrocyte sedimentation rate, white blood cell count and neutrophil count. RESULTS: YKL-40 serum levels were significantly higher in patients with psoriatic arthritis, compared to the control group. Moreover, a significant positive correlation between the activity of psoriatic arthritis measured by DAS 28 and serum level of YKL-40 was found. There was a positive correlation between serum YKL-40 and BSA, as well as a distinct trend towards significance between YKL-40 and PASI score. CONCLUSIONS: YKL-40 can be a useful biomarker for both diagnosing and monitoring joint involvement in psoriatic patients.

Increased interleukin (IL)-17 serum levels in patients with hidradenitis suppurativa: Implications for treatment with anti-IL-17 agents.

BACKGROUND: Biologics seem to offer a promising nonsurgical approach in hidradenitis suppurativa (HS), especially in disease with highly pronounced inflammation. Recent studies revealed increased expression of a broad range of cytokines in lesional HS skin, including interleukin (IL)-17. OBJECTIVE: This study was undertaken to determine IL-17 serum levels in this group of patients. METHODS: Our study was conducted on a group of 86 patients between 16 and 72 years of age with HS. A total of 86 matched healthy volunteers constituted the control group. Enzyme-linked immunosorbent assay kits were used to quantify IL-17 serum concentration. RESULTS: The mean IL-17 serum level of patients with HS was 3.68 ± 2.08 pg/mL, which was significantly elevated (P < .0001) compared with that found in healthy volunteers (2.5 ± 1.11 pg/mL). Moreover, there was a tendency toward higher serum concentrations of IL-17 in patients with more advanced disease (P = .005). Disease duration; patient sex, age, and body mass index; and smoking habits were not determining factors for IL-17 serum concentration. LIMITATIONS: Hospital-based study population was a limitation, as was a lack of posttreatment assessment. CONCLUSION: In light of our findings and literature on increased expression of IL-17 in HS lesions, evaluating the clinical effectiveness of using anti-IL-17 agents in the treatment of patients with HS is justified.

Chitinase-3-Like Protein 1 (YKL-40) Is a New Biomarker of Inflammation in Psoriasis.

PURPOSE: The evaluation of new inflammatory biomarkers in psoriasis could determine therapeutic decisions. Chitinase-3-like protein 1 (YKL-40) plays a role in inflammation. The study was undertaken to check whether YKL-40 is a reliable biomarker of inflammation in psoriasis. MATERIALS AND METHODS: 55 psoriatic patients were enrolled, including 21 men and 34 women, aged from 18 to 88 years. The PASI and body surface area were calculated for all patients. Blood samples were taken to evaluate serum concentration of YKL-40, as well as other inflammatory parameters, including CRP, ESR, white blood cell count, and neutrophil count. The measurements of YKL-40 level were performed by enzyme-linked immunosorbent assay (ELISA). RESULTS: YKL-40 serum concentration was significantly higher in psoriatic patients than in the control group. No correlations were found between YKL-40 levels and other clinical or laboratory parameters. Serum YKL-40 level was elevated in 81.8% patients, whereas CRP and WBC in 20% and 7.3% of patients, respectively. CONCLUSIONS: YKL-40 could be considered as a useful biomarker of inflammation in psoriasis and is more sensitive than CRP or WBC. Increased YKL-40 may indicate psoriatic patients with a higher level of systemic inflammation, which may determine disease management.

Serum Level of Protein-Bound Uraemic Toxins in Haemodialysis Patients with Chronic Kidney Disease-Associated Pruritus: Myths and Facts.

Recent studies place great importance on Protein-Bound Uraemic Toxins (PBUT) in the context of etiopathogenesis of chronic kidney disease-associated pruritus (CKD-aP). This study aimed to investigate the possible contribution of free and total Indoxyl Sulfate (IS) and p-Cresol Sulfate (PCS) to the cause of CKD-aP. Group A included 64 patients on maintenance haemodialysis (HD) with CKD-aP. Group B included 62 patients on maintenance HD that did not report CKD-aP, and group C included 50 healthy controls. Pruritus severity was assessed using a Numerical Rating Scale (NRS). Moreover, other tools like UP-Dial, ItchyQoL, and the 4-Item Itch Questionnaire evaluating CKD-aP were completed by the patients. The serum levels of free and total IS and PCS concentrations were measured using the Ultra Performance Liquid Chromatography System. No significant difference in the serum level of free and total IS, or PCS, was observed between the patients who reported CKD-aP and those without pruritus. Moreover, there was no correlation between serum IS or PCS levels and the severity of the itch. Our study does not support earlier findings about higher levels of IS and PCS in patients reporting CKD-aP. Further studies will be needed to investigate these discrepancies as well as to understand the cause of CKD-aP.

Endogenous Opioid Imbalance as a Potential Factor Involved in the Pathogenesis of Chronic Kidney Disease-Associated Pruritus in Dialysis Patients.

Chronic pruritus is one of the most common symptoms of dermatological diseases. It may occur in the course of other disorders, such as kidney disease. Chronic kidney disease-associated pruritus (CKD-aP) most often affects people with end-stage renal disease. The etiology of this condition is still not fully understood, but researchers are currently focusing on a thorough analysis of the association between disturbed opioid balance and increased neuronal signaling leading to pruritus. The aim of this study is to assess the concentration of endogenous opioids in dialysis patients with and without pruritus and in the control group, and to determine the correlation between the concentration of these substances and the occurrence and severity of itching. The study involved 126 dialysis patients and 50 healthy controls. Patients were divided into groups with pruritus (n = 62) and without pruritus (n = 64). The severity of pruritus was assessed using the NRS scale. The concentration of endogenous opioids was determined using the ELISA. The concentration of met-enkephalin was higher in the group of patients with pruritus compared to the control group. Moreover, significantly lower levels of ß-endorphin and dynorphin A were observed in the group of dialysis patients compared to the control group. In addition, a statistically significant difference was seen between the ß-endorphin concentration in the group of dialysis patients with pruritus compared to the group without pruritus. The ratio of ß-endorphin/dynorphin A concentrations was significantly lower in the group of patients with pruritus compared to patients without pruritus and the control group. No correlations were found between serum level of studied opioids and the severity of pruritus. The concentrations of the studied opioids did not correlate with the severity of pruritus. Observed opioid imbalance may affect the occurrence of CKD-aP in dialysis patients, but a thorough understanding of the mechanism of action of these substances in the sensation of pruritus is necessary to assess the possibility of finding a new therapeutic target.

Neurotrophin-4 and Brain-Derived Neurotrophic Factor Serum Levels in Renal Transplant Recipients with Chronic Pruritus.

INTRODUCTION: Chronic pruritus (CP) is a common symptom defined as a sensation that provokes the desire to scratch and which lasts for at least 6 weeks. CP remains a problem for up to 21.3% of renal transplant recipients (RTRs). Our research aimed to establish the possible association between serum levels of neurotrophin-4 (NT-4) and brain-derived neurotrophic factor (BDNF) and the presence and intensity of CP in RTR. METHODS: The study was performed on a group of 129 RTRs, who were divided according to the presence or absence of pruritus in the previous 3 days. The assessment of pruritus was performed with the use of a numeric rating scale (NRS), 4-Item Itch Questionnaire (4IIQ), and Itchy Quality of Life (Itchy QoL). A total of 129 blood samples with a volume of 9 ml were drawn from RTRs during the monthly routine control. Serum levels (pg/mL) of NT-4 and BDNF were measured by the ELISA. RESULTS: Pruritic RTRs have statistically significantly higher serum concentrations of NT-4 serum level compared to non-pruritic RTRs (229.17 ± 143.86 pg/mL and 153.08 ± 78.19 pg/mL [p = 0.024], respectively). Moreover, a statistically significant difference between pruritic and non-pruritic RTRs with healthy controls was shown (p < 0.001 and p < 0.001, respectively). Although there was a numerically higher serum concentration of BDNF in pruritic RTRs (32.18 ± 7.31 pg/mL vs. 31.58 ± 10.84 pg/mL), the difference did not reach statistical significance. No statistically significant difference was also seen in BDNF serum levels between RTRs and healthy controls. Furthermore, there was a statistically significant, positive correlation between serum concentration of NT-4 and NRS score (p = 0.008, r = 0.357). CONCLUSIONS: The results indicate higher NT-4 serum concentration in RTRs with pruritus compared to RTRs without pruritus. Furthermore, the study revealed a statistically significant, positive correlation between the serum concentration of NT-4 and NRS score.

The Serum Level of IL-31 in Patients with Chronic Kidney Disease-Associated Pruritus: What Can We Expect?

Chronic-kidney-disease-associated pruritus (CKD-aP) is one of the most common and burdensome dermatological symptoms affecting patients undergoing dialysis, and its etiopathogenesis has still not been fully discovered. This study was designed to investigate the possible contribution of interleukin-31 (IL-31) to the pathogenesis of itch in patients undergoing maintenance hemodialysis (HD). We evaluated the serum level of IL-31 in HD patients with pruritus, in HD patients without pruritus and in healthy controls, as well as its correlation to the severity of itch. The study enrolled 175 adult subjects. The participants were divided into three groups. Group A included 64 patients on maintenance HD with CKD-aP, Group B included 62 patients on maintenance HD not reporting CKD-aP and Group C included 49 healthy controls. Pruritus severity was assessed using the Numerical Rating Scale (NRS), and the serum levels of IL-31 were measured. The results showed that the IL-31 serum level was significantly higher in the itchy group (p < 0.001) in comparison to the patients free from pruritus. Moreover, a marginal trend towards significance (r = 0.242, p = 0.058) was observed between the IL-31 serum level and itch intensity. Our study supports earlier findings on the extended role of IL-31 in the development of CKD-aP.

High Serum IL-31 Concentration Is Associated with Itch among Renal Transplant Recipients.

Chronic itch (CI) is a common symptom caused by both dermatological and systemic disorders. CI is also a frequent, burdensome symptom among renal transplant recipients (RTR); however, its pathophysiology is not fully understood. The aim of this study was to assess the differences in concentration of IL-31 among itchy RTR. The study was performed on a group of selected 129 RTRs (54 itchy and 75 non-itchy patients). Itch severity was assessed with the use of the numeral rating scale (NRS) and the 4-item itch questionnaire (4IIQ). Every subject had his blood drawn to measure the concentration of IL-31. The results were subsequently compared and correlated. The mean concentration differed significantly between RTR suffering from itch (602.44 ± 534.5 pg/mL), non-itchy RTR (161.49 ± 106.61 pg/mL), and HC (110.33 ± 51.81 pg/mL) (p < 0.001). Post-hoc analysis revealed a statistically significantly increased IL-31 serum concentration in itchy RTR in comparison to the non-itchy RTR group (p < 0.001) and HC (p < 0.001). No significant difference was observed in IL-31 serum levels between non-itchy RTRs and HC. No correlation between IL-31 and itch intensity was found. The results of our study clearly demonstrate the association between IL-31 levels and CI in patients after renal transplantation.

Elevated Level of Serum Neurotrophin-4, but Not of Brain-Derived Neurotrophic Factor, in Patients with Chronic Kidney Disease-Associated Pruritus.

Chronic kidney disease-associated pruritus (CKD-aP) is a bothersome condition that occurs in patients with advanced chronic kidney disease (CKD) and severely reduces their quality of life. Recently, much research has focused on the search for markers that are involved in the pathogenesis of CKD-aP and may become a therapeutic target. One of the suggested hypotheses is the increased activation of sensory neurons by molecules such as neurotrophins (NTs). An increased serum concentration of NTs has been demonstrated in pruritic patients, which may suggest their involvement in the pathogenesis of itch. The purpose of this study is to assess the serum concentration of neurotrophin-4 (NT-4) and brain-derived neurotrophic factor (BDNF) in hemodialysis patients. The study enrolled 126 patients undergoing dialysis. Participants were divided into 2 groups: with and without CKD-aP. NRS scale was used to evaluate itch severity. Serum levels of NT-4 and BDNF have been assessed using ELISA. The results showed a significantly higher level of NT-4 in the group with pruritus. No significant difference was reported in the serum level of BDNF between the two groups of patients. There was also no correlation between serum NT-4 nor BDNF levels and the severity of pruritus. In summary, NT-4 may play an important role in the pathophysiology of pruritus in dialysis patients. More research is needed to understand the exact mechanism by which NTs influence the pathogenesis of CKD-aP.

Increased Serum Levels of S100A4 and S100A15 in Individuals Suffering from Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease. Recently, some S100 proteins have been suggested to play an important role in the pathogenesis of chronic immune-mediated inflammatory diseases and they may constitute valuable biomarkers for these diseases' diagnosis and monitoring. The objective of the current study was to investigate, for the first time, serum levels of S100A4 and S100A15 in individuals suffering from HS. Furthermore, we assessed the associations between S100A4 and S100A15 serum levels and the severity of disease, CRP serum concentration and some demographic and clinical data. Serum levels of S100A4 and S100A15 were evaluated with the commercially available ELISA kit according to the manufacturer's instructions. The serum level of S100A4 in individuals with HS was significantly elevated as compared to controls, with the highest level found in the individuals in Hurley stage II. The S100A15 serum level was positively correlated with the CRP concentration and was associated with the severity of the disease. The serum level of S100A15 in the individuals in Hurley stage III was significantly elevated compared to that of the controls and the individuals with HS in Hurley stages I and II. S100A4 and S100A15 may be considered as new serum biomarkers for the monitoring of HS progression, and they may play a role in the pathogenesis of HS by promoting inflammatory process and fibrosis.

Immunosuppression as a Hallmark of Critical COVID-19: Prospective Study.

The dysregulation of both the innate and adaptive responses to SARS-CoV-2 have an impact on the course of COVID-19, and play a role in the clinical outcome of the disease. Here, we performed a comprehensive analysis of peripheral blood lymphocyte subpopulations in 82 patients with COVID-19, including 31 patients with a critical course of the disease. In COVID-19 patients who required hospitalization we analyzed T cell subsets, including Treg cells, as well as TCRα/ß and γ/δ, NK cells, and B cells, during the first two weeks after admission to hospital due to the SARS-CoV-2 infection, with marked reductions in leukocytes subpopulations, especially in critically ill COVID-19 patients. We showed decreased levels of Th, Ts cells, Treg cells (both naïve and induced), TCRα/ß and γ/δ cells, as well as CD16+CD56+NK cells in ICU compared to non-ICU COVID-19 patients. We observed impaired function of T and NK cells in critically ill COVID-19 patients with extremely low levels of secreted cytokines. We found that the IL-2/INFγ ratio was the strongest indicator of a critical course of COVID-19, and was associated with fatal outcomes. Our findings showed markedly impaired innate and adaptive responses in critically ill COVID-19 patients, and suggest that the immunosuppressive state in the case of a critical course of SARS-CoV-2 infection might reflect subsequent clinical deterioration and predict a fatal outcome.

Chitinase-3-Like Protein 1 (YKL-40) Reflects the Severity of Symptoms in Atopic Dermatitis.

Chitinase-3-like protein 1 (YKL-40) is suggested to be associated with type 2 T helper response and atopy. The aim of the study was the evaluation of serum YKL-40 level in atopic dermatitis. The study was performed on 59 patients: 27 males and 32 females, aged from 18 to 64 years. The severity of the disease was assessed by the SCORAD and objective SCORAD indexes. The severity of pruritus was measured by the visual analogue scale. Blood samples were taken to examine serum level of YKL-40, total IgE level, C-reactive protein level, white blood cell count, and neutrophil count. YKL-40 serum levels were significantly higher in patients with atopic dermatitis compared to the controls. There was a positive correlation between YKL-40 concentration and SCORAD, objective SCORAD, and pruritus. This study has shown that YKL-40 serum level is increased in patients with atopic dermatitis and reflects the severity of symptoms.