Circulatory cytokeratin 17, marginal zone B1 protein and leucine-rich α2-glycoprotein-1 as biomarkers for disease severity and fibrosis in systemic sclerosis patients.

Introduction: Systemic sclerosis (Ssc) is a multiorgan debilitating autoimmune disease that associates the triad: vascular involvement, tissue fibrosis and profound immune response alterations. Numerous previous studies focused on identification of candidate proteomic Ssc biomarkers using mass-spectrometry techniques and a large number of candidate Ssc biomarkers emerged. These biomarkers must firstly be confirmed in independent patient groups. The aim of the present study was to investigate the association of cytokeratin 17 (CK17), marginal zone B1 protein (MZB1) and leucine-rich α2-glycoprotein-1 (LRG1) with clinical and biological Ssc characteristics. Material and methods: Serum CK17, MZB1 and LRG1 were assessed in samples of the available Ssc biobank comprising of samples from 53 Ssc patients and 26 matched age and gender controls. Results: Circulatory CK17, LRG1 and MZB1 concentrations were increased in Ssc patients. Cytokeratin 17 is independently associated with Ssc disease activity. Patients with pulmonary fibrosis expressed higher LRG1 and MZB1 concentrations. Serum MZB1 concentrations were also associated with extensive skin fibrosis. Conclusions: Serum CK17, MZB1 and LRG1 were confirmed biomarkers for Ssc. LRG1 seems a good biomarker for pulmonary fibrosis, while MZB1 is a good biomarker for extensive skin fibrosis. CK17 proved to be independently associated with Ssc disease severity, higher CK17 values being protective for a more active disease.

S100A6, Calumenin and Cytohesin 2 as Biomarkers for Cutaneous Involvement in Systemic Sclerosis Patients: A Case Control Study.

BACKGROUND: Systemic sclerosis (Ssc) is an autoimmune disease with incomplete known physiopathology. There is a high number of candidate proteomic biomarkers for Ssc that have not yet been confirmed on independent Ssc cohorts. The aim of the study was to confirm circulating S100A6, calumenin, and cytohesin 2 as biomarkers for Ssc. METHODS: 53 Ssc patients and 26 age- and gender-matched controls were included. Serum S100A6, calumenin, and cytohesin 2 were evaluated with commercial ELISA kits. Associations between serum expression and clinical Ssc characteristics were evaluated. RESULTS: Serum calumenin, S100A6, and cytohesin 2 were higher in Ssc patients compared to controls. Calumenin associated with extensive cutaneous fibrosis, frequency of Raynaud phenomenon, and low complement level, and had a tendency to be higher in Ssc patients with pulmonary fibrosis. S100A6 correlated with the number of active digital ulcers. Serum cytohesin 2 levels were higher in patients with teleangiectasia and associated with pulmonary artery pressure. CONCLUSIONS: Serum calumenin, S100A6, and cytohesin 2 were confirmed as biomarkers on an independent group of Ssc patients. Calumenin had the best predictive capacity for cutaneous Ssc manifestations. Future studies are needed to evaluate the prognostic value of these biomarkers and evaluate them as possible therapeutic targets.

Candidate proteomic biomarkers in systemic sclerosis discovered using mass-spectrometry: an update of a systematic review (2014-2020).

Background. Systemic sclerosis (Ssc) is an autoimmune disease characterized by graduate cutaneous and tissue fibrosis development and irreversible fibroproliferative vascular changes.The aim of the current systematic review was to update the list of proteomic candidate biomarkers identified from Ssc samples with mass spectrometry techniques.Methods. Medline and Scopus databases were searched on 1st September 2020. Relevant articles were searched from March 2014 until September 2020. Two independent reviewers evaluated the retrieved articles.Results. From a total of 97 articles, 9 articles were included in the final analysis summarizing 539 candidate proteomic biomarkers from various samples from Ssc patients (a larger number compared to the previous systematic review). Most biomarkers were identified from cutaneous biopsies. Only 5 articles included a validation step of the findings with only 13 biomarkers being validated.Conclusions. Although many candidate biomarkers were additionally identified, independent validation studies are needed in order to evaluate the importance of these biomarkers for Ssc patients.

Endocan and Lumican in Relation to Cardiometabolic Risk in a Pediatric Overweight and Obese Cohort: A Cross-Sectional Study.

The aim of the study was to evaluate serum Endocan and Lumican levels as biomarkers for pediatric Nonalcoholic Fatty Liver Disease (NAFLD) and to explore their associations with pediatric cardiometabolic risk factors. We conducted a cross-sectional study on 68 pediatric obese and overweight (O&O) patients. Ten healthy controls were recruited. Serum Lumican and Endocan levels were analyzed using ELISA kits. O&O patients had lower levels of Endocan compared to healthy controls (p < 0.001). There were no differences between serum Endocan levels in O&O patients with NAFLD and those without (p = 0.53). Patients considered having Nonalcoholic Steatohepatitis (NASH) had lower Endocan levels compared to O&O patients without NASH (p = 0.026). Patients with metabolic syndrome had lower levels of Endocan (p = 0.003). There were no significant differences between serum Lumican levels in O&O children compared to healthy controls. Lumican levels were higher in patients with hypertension (p = 0.04). In O&O patients, Lumican levels were negatively correlated with Endocan levels (r = -0.37, p = 0.002). Endocan seems a promising biomarker for the evaluation of pediatric NASH. Lumican was not confirmed as a biomarker for NAFLD in our cohort but was associated with higher arterial pressure. Low Endocan levels are accompanied by high serum Lumican levels, and this could be an early signature of cardiometabolic risk.

Circulating Hsp90 Isoform Levels in Overweight and Obese Children and the Relation to Nonalcoholic Fatty Liver Disease: Results from a Cross-Sectional Study.

BACKGROUND: Obesity prevalence is increasing in children. It is associated with various comorbidities including nonalcoholic fatty liver disease (NAFLD). Hsp90 isoforms were identified in previous proteomic studies as potential biomarkers for NAFLD. The aim of the study was to analyze circulating levels of Hsp90α and Hsp90ß in overweight and obese children. In addition, Hsp90α and Hsp90ß were evaluated as biomarkers for NAFLD in overweight and obese children. METHODS: 68 overweight and obese children and ten age- and gender-matched controls were recruited. Hsp90α and Hsp90ß levels were analyzed from serum in both controls and overweight and obese children by ELISA. RESULTS: Serum Hsp90ß and total Hsp90 levels were statistically significantly higher in overweight and obese children compared to controls. On the contrary, there was no difference in Hsp90α levels between overweight and obese children and healthy controls. Hsp90 isoforms had different expression in NAFLD patients. Hsp90ß levels were higher in overweight and obese NAFLD patients while Hsp90α levels were lower. Hsp90α to Hsp90ß ratio had better accuracy for NAFLD diagnosis in obese and overweight patients compared to individual biomarkers. CONCLUSION: Hsp90 isoforms were confirmed on an independent cohort as biomarkers for NAFLD in overweight and obese children. In these patients, it seems to be more useful to separately analyze Hsp90 isoforms rather than total Hsp90 as the isoforms have greater discriminative capacity.

Characteristics of shared decision making in Romania from the patient perspective: A cross-sectional multicentric study.

BACKGROUND: Shared decision making (SDM) is very important from patients' perspective. This process has not yet been evaluated in Romania. The study aims to evaluate SDM from the patients' perspective and to evaluate patients' characteristics that associate with SDM. MATERIAL AND METHODS: A cross-sectional multicentric study comprising eight recruitment centres was performed. Inpatients and outpatients who referred to Hospital Units treating autoimmune diseases or atrial fibrillation were included. Another sample consisted of members of the Autoimmune Disease Patient Society, who completed an online anonymous questionnaire. All participants completed the Romanian translated version of the 9-item Shared Decision Making Questionnaire (SDM-Q-9), as these samples were used for the validation of this questionnaire, too. Patients had to refer to the visit in which the decision concerning the antithrombotic treatment was taken (atrial fibrillation patients), or the immunosuppressive treatment was last time changed (autoimmune disease patients). Ordinal regression having the total SDM score as dependent variable was used. RESULTS: A total of 665 questionnaires were filled in within the hospital setting (n = 324; 48.7%) and online (n = 341; 51.3%). The median score for SDM was 34 of 45, but it differed between hospital completion -39/45 and online completion (anonymous) -20/45 (P < .001). Patients with higher education were influenced most by the setting, giving the best marks in hospital and low marks online, while those with lower education gave lower marks in both settings. In ordinal regression with SDM score as dependent variable, hospital completion of the questionnaire (OR = 9.5, 95% confidence interval, 5.69-16), collagen disease diagnosis (OR = 2.4, 95% confidence interval, 1.39-4.14), and immunosuppressive treatment (OR = 2.16, 95% confidence interval, 1.43-3.26) were independent predictors. CONCLUSION: In our study, full anonymity was associated with significantly lower scores for the SDM process. The patients with higher education were most influenced by this condition, while those with the lowest education were the most critical.

Romanian version of SDM-Q-9 validation in Internal Medicine and Cardiology setting: a multicentric cross-sectional study.

BACKGROUND: Shared decision making (SDM) is becoming more and more important for the patient-physician interaction. There has not been a study in Romania evaluating patients' point of view in the SDM process yet. Therefore, the present study aims to evaluate the psychometric parameters of the translated Romanian version of SDM-Q-9. MATERIAL AND METHODS: A multicentric cross-sectional study was performed comprising eight recruitment centers. The sample consisted of in- and outpatients who referred to Hospital Units for treatment for atrial fibrillation or collagen diseases. Furthermore, patients who were members of Autoimmune Disease Patient Society were able to participate via an online survey. All participants completed the Romanian translated SDM-Q-9. RESULTS: Altogether, 665 questionnaires were filled in within the hospital setting (n = 324; 48.7%) and online (n = 341; 51.3%). The Romanian version had good internal consistency (Cronbach α coefficient of 0.96.) Corrected item correlations were good ranging from 0.64 to 0.89 with low corrected item correlations for item 1 and item 7. PCA found a one-factorial solution (similar with previous reports) but the first item had the lowest loading. CONCLUSION: SDM-Q-9 is a useful tool for evaluation and improvement in health care that was validated in Romania and can be used in clinical setting in this country.

Salivary biomarkers of inflammation in systemic lupus erythematosus.

Saliva is currently used as a reliable diagnostic fluid in a wide range of local and systemic diseases. However, the link between salivary diagnosis and the inflammatory process in autoimmune diseases has not yet been explored. The aim of our study is to assess possible correlations between salivary inflammatory markers and systemic lupus erythematosus (SLE). Patients fulfilling the Systemic Lupus International Collaborating Clinics (SLICC) diagnosis criteria were included. Salivary and serum levels of interleukin-6 (IL-6), leptin, monocyte chemoattractant protein-1 (MCP-1) and plasminogen activator inhibitor-1 (PAI-1) were determined using stochastic sensors. Serum leptin and IL-6 had significantly higher levels in SLE patients compared to non-SLE. Also, salivary IL-6 levels highly correlated with the serum IL-6 levels. A positive correlation was found between salivary and serum levels of IL-6, signaling salivary IL-6 as a reliable marker for assessing the inflammation process in SLE.

IL-17 and Th17 cells in systemic sclerosis: a comprehensive review.

T cells (especially T helper cells) seem to be strongly associated with systemic sclerosis pathogenesis. Th17-IL-17 axis was proved to be involved in the pathogenesis of multiple autoimmune diseases. By performing a comprehensive research of the literature indexed in PubMed database, the current review summarizes current knowledge related to Th17 and IL-17 in systemic sclerosis. While there is promising data suggesting inhibition of Tregulatory and Th1 signals on one hand and promotion of Th17 and Th2 signals on the other, studies that include prospective and integrated analysis of Tregulatory, Th17, Th1, Th2 (cells and derived cytokines) on the same cohort of Ssc patients are warranted.

Circulating Reticulocalbin 1 and Reticulocalbin 3 in Systemic Sclerosis Patients: Results of a Case Control Study.

BACKGROUND: Proteomic candidate biomarkers for systemic sclerosis (Ssc) useful for appropriate patient evaluation and follow-up were identified in mass-spectrometry studies; however, most of these biomarkers were not evaluated and confirmed on independent patient samples. Up-regulation of reticulocalbin 1 (RCN1) and reticulocalbin 3 (RCN3) in the dermal fibroblast secretome originating from Ssc patients was previously described. The aim of the study was to evaluate circulating RCN1 and RCN3 as candidate biomarkers for Ssc clinical expression. METHODS: 40 consecutive Ssc patients and 20 gender and age matched controls were included. Serum RCN1 and RCN3 was evaluated using commercial ELISA kits. RESULTS: Serum RCN1 and RCN3 were not statistically significant different between Ssc patients and healthy controls. Serum RCN1 and RCN3 were correlated in both Ssc and healthy control groups (p < 0.001). Serum RCN1 was positively correlated with Ssc disease activity score (EUSTAR, p = 0.02) and remained associated with EUSTAR after adjusting for disease duration in multivariate analysis. 6 Ssc patients (15%) had elevated RCN1 values compared to reference values obtained from healthy control samples. These patients had higher prevalence of digital ulcers, higher disease activity scores, and tended to have esophageal hypomotility, calcinosis, telangiectasia, and diffuse Ssc subtype. CONCLUSIONS: RCN1 and RCN3 expression was not statistically significantly different to healthy controls. However, RCN1 was associated with disease activity score and could be used as a stratification biomarker for Ssc patients, as patients with high RCN1 shared a particular disease pattern.

Endocan, Novel Potential Biomarker for Systemic Sclerosis: Results of a Pilot Study.

BACKGROUND: Systemic sclerosis (Ssc) is an autoimmune disease characterized by vascular alterations of small arteries and microvessels with subsequent tissue fibrosis. Endocan is expressed by endothelial cells and associated with endothelial dysfunction; therefore it could be a potential biomarker for Ssc patients. METHODS: Twenty-one Ssc patients and 20 sex- and age-matched healthy controls were recruited for the study. Serum endocan levels were determined using ELISA method in all patients and controls. RESULTS: Serum endocan levels were superior in Ssc patients (median 2.53 (1.10-7 ng/ml)) compared with controls (0.79 (0-2 ng/ml), P < 0.05). Higher serum endocan expression was seen in diffuse Ssc subset and associated with the presence of digital ulcers and daily Raynaud's phenomenon (P < 0.05). Higher serum endocan levels were associated with a modified Rodnan skin score >14 and longer disease duration (P < 0.05). Values of areas under the receiver operating curves showed that serum endocan had good discriminative power for Ssc diagnosis, differentiating diffuse from limited subset type and differentiating patients with modified Rodnan skin score above and under 14 (area under curve: 0.94, 0.81, 0.75, respectively). CONCLUSION: The results of this pilot study suggest endocan as a potential biomarker for microvascular manifestations and complications in Ssc patients. These encouraging results could promote future prospective studies in order to determine the exact role played by endocan as a biomarker for Ssc.

IL-17, IL-6 and IFN-γ in Systemic Sclerosis Patients.

BACKGROUND: Systemic sclerosis (Ssc) is an autoimmune disease characterized by cutaneous and visceral fibrosis and its pathogenesis is incompletely understood. T helper cells are key regulators of the immune response and they seem to be involved in Ssc clinical manifestations. The aim of the study is to determine key cytokines secreted by Th1 (IFN-γ), Th2 (IL-6) and Th17 (IL-17) in Ssc patients and correlate them with specific manifestations of Ssc patients. MATERIAL AND METHODS: 35 consecutive Ssc patients and 20 age and sex matched controls were recruited. Serum IL-17, IFN-γ and IL-6 were determined using ELISA method. RESULTS: Serum IL-17 and IL-6 levels were not significantly different in Ssc patients and controls. Serum IFN-γ levels were higher in Ssc patients when compared to controls. Higher serum IFN-γ levels associated with pulmonary hypertension. After adjusting for gender and age, IL-17 levels remained independently associated with some clinical manifestations of Ssc patients (telangiectasia and high activity score of Ssc). CONCLUSION: Th17 and Th1 cell responses are active in Ssc patients as their cytokines associated with higher disease activity scores and pulmonary manifestations. Th17 and Th1 specific activity and homing within Ssc patients still needs to be defined and determined in order to target them as potential future therapeutic targets in Ssc patients.

Association of anti phosphatidyl ethanolamine antibodies and low complement levels in systemic sclerosis patients--results of a cross-sectional study.

Some systemic sclerosis (Ssc) patients express antiphospholipid antibodies and their percentage varies within studies in the literature. The particular role of these antibodies in clinical manifestations of Ssc is still unknown. The aim of the study was to examine an extended panel of antiphospholipid antibodies in Ssc patients who did not have any clinical features of antiphospholipid antibody syndrome. A cross-sectional study was designed and 36 consecutive patients with Ssc were recruited. A relatively high proportion of patients (14 patients - 38.9%) had antiphospholipid antibody presence. Most Ssc patients (11 patients - 30.6%) had IgM anti phosphatidyl ethanolamine antibodies. Serum IgM anti phosphatidyl ethanolamine antibodies, IgM anti prothrombin and IgG anti ß2 glycoprotein 1 antibodies were associated with low complement levels in Ssc patients. In multivariate analysis, only serum IgM anti phosphatidyl ethanolamine antibodies concentration and serum IgG anti ß2 glycoprotein 1 antibodies concentration were independently associated with hypocomplementemia after adjusting for age and gender. No other correlations with Ssc clinical characteristics were found. In conclusion, antiphospholipid antibodies are present in a large proportion of Ssc patients who do not have clinical features or a history of antiphospholipid antibodies. IgM anti phosphatidyl ethanolamine antibodies seem to be more frequent and the dominant antiphospholipid antibody type in the group recruited from the Romanian Ssc population.

Extended Antiphospholipid Antibodies Screening in Systemic Lupus Erythematosus Patients.

BACKGROUND: The antiphospholipid syndrome (APS) is one of the most encountered autoimmunity in systemic lupus erythematosus (SLE) patients and pathogenesis of these two seems to be intricate. AIM: To investigate the association of antiphospholipid antibodies (APLAs) titer with the presence of secondary APS diagnosis in SLE patients. METHODS: 65 patients fulfilling the 2012 Systemic Lupus Collaborating International Clinics (SLICC) SLE's criteria were included. The APS diagnosis was sustained according to the 2006 Sydney APS's criteria. Three groups of patients were defined: SLE patients with secondary APS, SLE with history of positive "criteria" APLAs but without APS clinical features, respectively SLE patients without positive APLAs or clinical APS criteria. An extended APLAs panel was searched in all cases: both IgM and IgG of anticardiolipin antibodies (aCL), anti-P2 glycoprotein I antibodies (aß2GPI), antiphosphatidylethanolamine antibodies (aPE), antiphosphatidylserine antibodies (aPS), respectively antiprothrombin antibodies (aPT). Results. Only the aß2GPI, both IgM and IgG serotypes, had significantly higher titers in patients with SLE and secondary APS compared to no APS (with/ without positive APLAs): median (min; max) 7.0 (0.0-300.0) vs. 1.0 (0.0-28.0) vs. 1.0 (0.0-12.0), respectively 3.0 (0.0-79.0) vs. 1.0 (0.0-3.0) vs. 1.0 (0.0-12.0) (p<0.001, Kruskal-Wallis test)]. Also, in regression logistic models, only the aß2 GPI (IgG and IgM ) were identified as risk factors for secondary APS diagnosis in the SLE patients: OR(95%CI) 5.9 (2.2-15.7), respectively 1.3 (1.1-1.5). In regard with the SLE markers, the IgG serotypes of the "non-criteria" APLAs analyzed (aPS, aPT, aPE) were correlated with the antiDNA titers while the IgM serotypes inversely associated with the complement C3 levels. CONCLUSIONS: IgG aß2 GPI are accompanied by almost 6-fold increase risk of secondary APS when screening SLE patients. On the contrary, the "non-criteria" APLAs do not seem associated with the APS diagnosis in SLE patients. Some correlates of the "non-criteria" APLAs with the antiDNA and complement C3 levels were also observed.

Systemic sclerosis biomarkers discovered using mass-spectrometry-based proteomics: a systematic review.

CONTEXT: Systemic sclerosis (SSc) is an autoimmune disease with incompletely known physiopathology. There is a great challenge to predict its course and therapeutic response using biomarkers. OBJECTIVE: To critically review proteomic biomarkers discovered from biological specimens from systemic sclerosis patients using mass spectrometry technologies. METHODS: Medline and Embase databases were searched in February 2014. RESULTS: Out of the 199 records retrieved, a total of 20 records were included, identifying 116 candidate proteomic biomarkers. CONCLUSION: Research in SSc proteomic biomarkers should focus on biomarker validation, as there are valuable mass-spectrometry proteomics studies in the literature.

Th17 and IL-17 immunity in chronic hepatitis C infection.

Hepatitis C virus (HCV) is one of the most important etiologic agents of postransfusional hepatitis and a common cause of chronic hepatitis, cirrhosis and hepatocarcinoma. T helper (Th)17 cells are a newly discovered Th cell subset with implications in both host defense and autoimmunity. Th17 implications in chronic HCV infection are not well characterized. Given the important role in multiple other immune and inflammatory conditions, they are of obvious interest. Specific HCV-Th17 cells are implicated in immune response modulation, correlated with fibrosis severity and intrahepatic inflammatory status. Serum IL-17 levels are higher in chronic HCV infected patients and Th17 cytokines are modulated within the therapeutic response at anti-viral treatment. However, novel intriguing data indicate that Th17 boost could be associated with spontaneous HCV clearance. It is possible that Th17 could play a dual role (both beneficial and harmful) and that an unbalance of regulating factors (chemokines, transcription factors, receptor expression, etc.) rather than the lymphocyte itself could tip the Th17 immune response one way or another. The role of Th17 cells in host anti HCV defense is beginning to emerge and one has to focus upon its potential beneficial aspects and not only on its destructive potential.

Hepatitis C virus-mixed cryoglobulinemia-lymphoma relationship.

HCV (hepatitis C virus) chronic hepatitis has become one the most expensive diseases for public health systems all over the world in the past 10-20 years, a real epidemic, the second most frequent, after hepatitis B virus infection. Due to the complex manifestations, one may consider HCV infection as a "systemic" disease. Mixed cryoglobulinemia (MC) is the most common extrahepatic manifestation of HCV infection, but cryoglobulinemic vasculitis (CV) is considered to be relatively sparse although prevalence studies are needed. Presence of serum cryoglobulins is essential for MC diagnosis, but serum levels do not correlate with the disease activity or prognosis. MC can be defined as a B lymphocyte proliferation disease being characterized by polyclonal activation and antibody synthesis. Evolution to lymphoma should be considered continuous but also other infectious, environmental or genetic factors could be involved. The t (14.18) translocation and Bcl-2 activation in B lymphocytes, B cell-activating factor (BAFF), E2-CD81 interaction, immunoregulatory T CD4+CD25(high) + lymphocytes and type III IFNs might play an important role in MC and lymphoma evolution in HCV patients.

Anti C1q antibodies in cutaneous lupus erythematosus.

UNLABELLED: Autoantibodies against C1q are strongly linked to immune-complex disorders like systemic lupus erythematosus (SLE). Although anti-C1q antibodies have received much interest in the recent years, their biological functions remain unclear. Anti-C1q antibodies are strongly associated with lupus nephritis. Recent studies describe apoptosis as a key player in LE pathogenesis and C1q is an important opsonin, playing a central role in the uptake of apoptotic blebs. The aim of this study was to evaluate serum anti C1q antibodies, C1q with circulating immune complexes and correlation between serology and cutaneous apoptosis in patients with cutaneous lupus erythematosus. MATERIAL AND METHODS: 79 subjects were recruited and divided into 4 groups-13 healthy controls, 26 with discoid chronic lupus (DLE), 23 with systemic lupus erythematosus (SLE) and 17 with subacute lupus erythematosus (SCLE). Blood samples and skin punched-biopsy specimens were performed. Serum anti-C1q antibodies and C1q associated to the immune complexes concentrations were determined by ELISA. Cutaneous caspase-3 expression was evaluated by immunohistochemistry. RESULTS: SLE and SCLE patients had significantly higher levels of anti-C1q antibodies and serum C1q-CIC levels when compared to healthy controls (p < 0.05). Serum anti-C1q antibodies correlated with proteinuria in SLE patients (p < 0.05). Anti C1q antibodies levels also correlated with cutaneous caspase 3 expression in SLE and SCLE patients (both p < 0.05). CONCLUSIONS: Anti C1q antibodies might play a pathogenic role in SCLE pathogenesis and being positively associated with cutaneous apoptosis markers might be associated with a negative prognosis and secondary SLE development.

T helper 17 cell population in lupus erythematosus.

UNLABELLED: Lupus erythematosus (LE) is an autoimmune inflammatory disease that involves many organs and systems. Immunological factors seem to play a key-role in LE pathogenesis. LE patients have T lymphocytes dysfunctions.Th17 is implicated in the pathogenesis of various autoimmune diseases like psoriasis, multiple sclerosis or rheumatoid arthritis. The purpose of this study was to evaluate the circulating Th17 cell population in LE patients. MATERIAL AND METHODS: A total of 15 LE patients were recruited and divided into three groups: systemic lupus erythematosus (SLE), discoid lupus (DLE) and subacute lupus (SCLE). Serum IL-17A, IL-17F and IL-23 were detected. Th17 circulating cells were evaluated by flow cytometry. RESULTS: Serum IL-17A and IL-17F levels were higher in SLE, DLE and SCLE patients compared to healthy controls. The number of Th17 cells were higher in SLE and DLE patients (p<0.05). the number of CD3+IL-17+ cells were higher in SLE, DLE and SCLE patients (p<0.05). CONCLUSION: Th17 lymphocytes are implicated in LE pathogenesis. Our findings suggest that IL-17 is implicated not only in SLE but also in DLE and SCLE immunopathogenesis.

Immunohistochemical aspects of apoptosis in subcutaneous lupus erythematosus.

UNLABELLED: Lupus erythematosus (LE) has a broad clinical spectrum from exclusively skin damage (chronic discoid lupus-DLE or subacute lupus erythematosus-SCLE) to systemic, multiorgan disease (involving skin, joints, kidney, central nervous system). LE is characterized by an autoimmune component. SCLE is characterized by erythemato-squamous lesions mainly in photoexposed areas. Apoptosis (programmed cellular death) is essential for normal embryogenesis and for normal tissue homeostasis and control. Inefficient apoptotic cell clearance has been correlated with inflammatory diseases and autoimmunity outburst. This study evaluates histological and immunohistochemical expression ofpro-apoptotic markers in patients with SCLE. MATERIALS AND METHODS: 20 patients with SCLE and 10 healthy controls were selected. Biopsies from skin lesions were performed. Biopsies were evaluated for immunohistochemical expression of caspase 3, CD25, CD35, CD21, CD36, CD68, CD31, IgM detection, T and B cell markers. RESULTS: In the inflammatory cells population we distinguished T lymphocytes, rare B lymphocytes, dendritic cells and macrophages. Within the lymphocyte population IL-2 receptor (CD25) expression was low but caspase 3 expression was intense in lymphocytes, epithelial cells and pericytes. Basal epithelial vacuolations were common. Phagocytic-cell and lymphocytic expression of CD35 (complement receptor 1-CR1) and CD21 (complement receptor 2-CR2) were lower when compared to healthy controls. CONCLUSIONS: In SCLE patients we observed lymphocytic, epithelial and pericytal cell apoptosis and CR1 and CR2 expression are lower in professional phagocytes, suggesting a delay in the uptake of apoptotic bodies.