Rapid Fecal Calprotectin Testing Predicts Mucosal Healing Better than C-reactive Protein and Serum Tumor Necrosis Factor α in Patients with Ulcerative Colitis.

BACKGROUND AND AIMS: Serum and fecal biomarkers have been used as noninvasive methods for assessing disease activity in ulcerative colitis. C-reactive protein, serum tumor necrosis factor-α and fecal calprotectin are among the most promising such biomarkers. However, their role in the management of ulcerative colitis patients remains to be clarified. We aimed to evaluate the accuracy of C-reactive protein, fecal calprotectin and tumor necrosis factor-α in detecting clinical and endoscopic activity and predicting disease outcome. METHODS: A cohort of ulcerative colitis patients was prospectively evaluated for clinical and endoscopic disease activity using the Mayo score. Serum C-reactive protein and tumor necrosis factor-α levels were measured and a point-of-care method was used for determining Calprotectin levels. RESULTS: Fifty-three patients with ulcerative colitis were followed for a median of 12 months. Fecal calprotectin and C-reactive protein levels were significantly higher in patients with clinically active disease at baseline, but only calprotectin levels correlated with endoscopic activity. Calprotectin values over 300 µg/g had 60% sensitivity and 90% specificity for detecting active endoscopic disease and 61% sensitivity and 89% specificity for predicting mucosal healing. CONCLUSION: Rapid calprotectin testing is a better predictor of mucosal healing than serum biomarkers and it could improve the management of ulcerative colitis patients by decreasing the need for invasive investigations.

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.

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.

Pharmacological treatment in calcinosis cutis associated with connective-tissue diseases.

BACKGROUND: Dystrophic calcinosis cutis is a common manifestation in connective tissue diseases, but there's still no consensus on treatment. OBJECTIVES: The purpose of this review is to discuss the current pharmacological options of treatment in calcinosis cutis related to rheumatic diseases. METHOD: We performed an extensive MEDLINE search of articles from 1970 to January 2014 using the index word "calcinosis" and the co-indexing terms "treatment", "calcium channel blocker", "diltiazem", "nifedipine", "verapamil", "amlodipine", "anticoagulant", "warfarin", "bisphosphonate", "etidronate", "pamidronate", "alendronate", "risedronate", "aluminum hydroxide", "probenecid", "antibiotic", "tetracycline", "minocycline", "ceftriaxone", "colchicine", "intravenous immunoglobulin", "sodium thiosulfate", "TNF-alpha inhibitors", "infliximab", "rituximab", "thalidomide", "corticosteroids", "stem cell transplantation". RESULTS: Diltiazem is recommended by some authors as first-line approach in calcinosis cutis and is also the therapeutic principal referred by the largest number of available publications. It seems to be efficient in more than half of the reported cases. There remain, however, a significant number of patients in which another solution must be found. The general trends observed over time are of switching the search of solutions in dystrophic calcinosis cutis related to connective tissue diseases, from therapies on calcium metabolism to therapies for the underlying disease. The new options available in the management of calcinosis cutis, like biological therapies or intravenous immunoglobulin, seem to be promising, but not universally successful. In children with severe forms, hematopoietic stem cell transplantation can also be taken into consideration. CONCLUSIONS: Data for all therapies proposed in calcinosis cutis is generally reported in single cases and small case series and so, the existent data is all yielding a low level of evidence.

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.

IL-17 in cutaneous lupus erythematosus.

BACKGROUND: Lupus erythematosus (LE) is a heterogeneous disease with broad clinical spectrum from cutaneous to visceral and systemic inflammation. IL-17 isoforms (IL-17A and IL-17F) are proinflammatory cytokines with unclear implications in lupus erythematosus pathogenesis. In this study we focused upon IL-17 in normal and modified lupus skin with a correlative study between local and serological expression. MATERIAL AND METHODS: 89 subjects were recruited and divided in 5 groups-10 patients with psoriasis (disease control group), 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 IL-17A, IL-17F, and IL-23 concentrations were determined by ELISA. Skin IL-17A and CD4 expression were evaluated by immunohistochemistry. RESULTS: Immunohistochemical expression of IL-17A was higher in DLE, SCLE and SLE patients than in negative control subjects (all p<0.05). Serum IL-17A concentrations were higher in DLE and SLE patients than in negative controls (p<0.05). Serum IL-17A levels were similar in SCLE and negative controls (p>0.05). Serum IL-17F concentrations were higher in DLE, SCLE and SLE patients than in healthy controls (all p<0.05). In DLE, SCLE, SLE patients and healthy controls we observed comparable levels of IL-23 (p>0.05). Serum anti Ro antibodies correlate with IL-17A+ lymphocytes from SCLE lesion and SLE normal skin (all p<0.05). CONCLUSION: IL-17 isoforms (IL-17A and IL-17F) are implicated in SLE but also in DLE and SCLE immunopathogenesis.

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.