A portable dermatoscope for easy, rapid examination of periungual nailfold capillary changes in patients with systemic sclerosis.

Microvascular lesions are a predominant feature in systemic sclerosis (SSc) and seem to play a central pathogenic role. The presence of nailfold capillary abnormalities is useful in diagnosing SSc. Capillaroscopy, however, usually requires special equipment and may be time consuming. Dermatoscope has been presented as a new diagnostic tool for quick and efficient examination of nailfold capillaries for circumstances when standard microscope equipment is not available. To assess the practical utility of dermatoscope for assessment of capillary morphology in patients with SSc, 83 Japanese patients with SSc (68 women, 15 men) and 68 healthy controls were examined in the study. Twenty-one patients (16 women, 5 men) had diffuse cutaneous SSc and 62 (52 women, 10 men) had limited cutaneous SSc. Enlarged capillaries and hemorrhages were evaluated in all 10 fingers with either naked eyes or DermLite((R)) DL100 dermatoscope. Enlarged capillaries and hemorrhages were significantly more frequently detected with dermatoscope than without it. These findings were observed most frequently in the fourth finger. The presence of two or more enlarged capillaries in one or more fingers showed 83.1% sensitivity and 100% specificity for SSc. Among patients with SSc with anti-topoisomerase I antibody, the disease duration correlated negatively with the dermatoscopic number of enlarged capillaries and hemorrhages. Dermatoscope allows the easy and rapid identification of capillary nailfold morphological changes in SSc and should be routinely used for diagnosing SSc.The original publication is available at www.springerlink.co

CCL13 is a promising diagnostic marker for systemic sclerosis.

Summary Background Previous studies suggest that CCL13 may have some role in the pathogenesis of systemic sclerosis (SSc). Objectives To determine serum levels of CCL13 and its clinical associations in patients with SSc. Methods Serum CCL13 levels were examined by enzyme-linked immunosorbent assay in 80 patients with SSc, 20 patients with systemic lupus erythematosus (SLE), 20 patients with dermatomyositis (DM), 29 patients with atopic dermatitis (AD) and 50 healthy individuals. Results Mean +/- SD serum CCL13 levels were elevated in patients with SSc (81.3 +/- 55.8 pg mL(-1)) compared with healthy controls (15.0 +/- 9.9 pg mL(-1); P < 0.001) and patients with SLE (22.0 +/- 6.9 pg mL(-1); P < 0.001), DM (24.4 +/- 36.1 pg mL(-1); P < 0.001) and AD (18.0 +/- 6.4 pg mL(-1); P < 0.001). Among patients with SSc, there were no differences in serum CCL13 levels between limited cutaneous SSc and diffuse cutaneous SSc. In a longitudinal study, CCL13 levels were generally unchanged during the follow-up. Conclusions Serum CCL13 was specifically increased in patients with SSc, but not in patients with SLE, DM or AD or in healthy controls. CCL13 could be a promising serological marker for SSc

Involvement of gaseous low molecular monoxides in the cutaneous reverse passive Arthus reaction: cytoprotective action of carbon monoxide.

The deposition of immune complexes (IC) induces an acute inflammatory response with tissue injury, for which the involvement of nitric oxide (NO) and carbon monoxide (CO) has been suggested. NO is induced by NO synthase (NOS) and CO is generated by haeme oxygenase (HO). Among HO isoenzymes, HO-1 is an induced type. To assess the role of NO and CO in the pathogenic process, the cutaneous reverse passive Arthus reaction was examined using NOS inhibitor, HO-1 stimulator and HO-1 inhibitor. To evaluate the reaction we considered oedema, tumour necrosis factor-alpha, interleukin-6, and neutrophil number. The values of these four parameters were significantly reduced in mice treated with HO-1 stimulator as compared with the positive control mice. Quite the reverse was observed in mice treated with HO-1 inhibitor. These results suggest that the HO-1/CO signalling pathway is a therapeutic target for human IC-mediated disease

Decreased levels of autoantibody against histone deacetylase 3 in patients with systemic sclerosis.

Systemic sclerosis (SSc) is characterized by immunological abnormalities, especially the production of autoantibodies against various cellular components. Treatment with histone deacetylase (HDAC) inhibitors prevents collagen accumulation in a mouse SSc model. Additionally, autoantibody against HDAC-3 is produced in colon cancer patients, while HDAC-1 and HDAC-2 do not elicit autoantibody response. To determine the presence and levels of antibodies (Abs) against HDAC-3 in SSc. Anti-HDAC-3 Ab was examined by enzyme-linked immunosorbent assay (ELISA) and immunoblotting using human recombinant HDAC-3. The HDAC-3 activity was evaluated by ELISA using the fluorimetric HDAC lysyl substrate that comprises an acetylated lysine side chain. Contrary to our hypothesis that autoimmune background in SSc induced the production of autoantibody against HDACs, IgG and IgM anti-HDAC-3 Ab levels in SSc patients were significantly lower than in normal controls (p < 0.0005 and 0.001, respectively). Furthermore, decreased levels of IgG anti-HDAC-3 Ab were specific to SSc, since IgG anti-HDAC-3 Ab levels in patients with dermatomyositis (DM) and those with systemic lupus erythematosus (SLE) were similar and slightly increased relative to normal controls, respectively. Immunoblotting analysis showed that anti-HDAC-3 Ab was detected in normal controls and patients with DM or SLE, while it was absent in SSc patients. The HDAC-3 activity was significantly inhibited by IgG isolated from sera of normal controls, whereas such inhibitory effect was not observed by IgG isolated from sera of SSc patients. These results indicate the lack of anti-HDAC-3 autoantibody in SSc patients, which is produced in healthy individuals as well as DM and SLE patients, suggesting that this autoantibody might function as protective Ab.This is an electronic version of an article published in Free Radical Research, 42(11-12), 957-965: 2008 November. Free Radical Research is available online at: http://informahealthcare.com/doi/abs/10.1080/0891693080240630

The differential role of L-selectin and ICAM-1 in Th1-type and Th2-type contact hypersensitivity.

Sensitization and challenge using DNFB induce contact hypersensitivity (CHS) with predominant type 1 helper (Th1) cell infiltration, whereas those using FITC generate CHS with Th2 cell infiltration. CHS results from inflammatory cell infiltration, a process that is highly regulated by the expression of multiple adhesion molecules. We attempted to determine the role of L-selectin and ICAM-1 in Th1- and Th2-type CHS induced by DNFB or FITC in mice lacking either L-selectin, ICAM-1, or both. Th1-type CHS induced by DNFB was inhibited by L-selectin and/or ICAM-1 deficiency, which was associated with reduced IFN-gamma expression. Similarly, Th2-type CHS induced by FITC was inhibited by L-selectin deficiency. However, Th2-type CHS was increased by ICAM-1 deficiency and accompanied by increased Th2 cytokine expression. Infiltration of in vitro-generated Th1 cells into the FITC-challenged skin decreased in ICAM-1-deficient mice, whereas in vitro-generated Th2 cell infiltration increased, suggesting that ICAM-1 mediates Th1 cell migration and that in the absence of ICAM-1, Th1 cell recruitment decreased, whereas relative Th2 cell migration increased. These results suggest that ICAM-1 mediates Th1 cell recruitment irrespective of DNFB or FITC and that L-selectin recruits Th1 cells in Th1-type CHS, whereas it recruits Th2 cells in Th2-type CHS

P-selectin glycoprotein ligand-1 contributes to wound healing predominantly as a p-selectin ligand and partly as an e-selectin ligand.

Cell adhesion molecules are critical to wound healing through leukocyte recruitment. Although P-selectin glycoprotein ligand-1 (PSGL-1) regulates leukocyte rolling by binding P-selectin, but also binding E- and L-selectins with lower affinity, little is known about a role of PSGL-1 in wound healing. To clarify a role of PSGL-1 and its interaction with E- and P-selectins in wound healing, we investigated cutaneous wound healing in PSGL-1-deficient (PSGL-1(-/-)) mice in comparison with E-selectin(-/-), P-selectin(-/-), and P-selectin(-/-) mice treated with an anti-E-selectin antibody. PSGL-1 deficiency inhibited early wound healing, which was accompanied by decreased inflammatory cell infiltration and growth factor expression. By contrast, E-selectin deficiency did not affect wound healing. In general, the inhibitory effect of PSGL-1 deficiency on wound healing was similar to that of P-selectin deficiency either alone or with E-selectin blockade. However, early granulation tissue formation, late angiogenesis, and early infiltration of neutrophils and macrophages in PSGL-1(-/-) mice were inhibited beyond the inhibition in P-selectin(-/-) mice, but to a similar level of inhibition in P-selectin(-/-) mice with E-selectin blockade. These results suggest that PSGL-1 contributes to wound healing predominantly as a P-selectin ligand and partly as an E-selectin ligand by mediating infiltration of inflammatory cells

Autoantibodies against matrix metalloproteinase-1 in patients with localized scleroderma

Background: Localized scleroderma (LSc) is characterized by cutaneous fibrosis and various autoantibodies. Objective: To determine the presence or levels of antibodies (Abs) against matrix metalloproteinase (MMP)-1 and their clinical relevance in LSc. Methods: Anti-MMP-1 Ab was examined by ELISA (Enzyme-Linked ImmunoSorbent Assay) and immunoblotting using human recombinant MMP-1. MMP-1 collagenase activity was determined using biotinylated collagen as substrate and the amount of cleaved biotinylated fragments of collagen by MMP-1 was measured by ELISA. Results: LSc patients exhibited significantly elevated IgG anti-MMP-1 Ab levels relative to normal controls at similar level of patients with systemic sclerosis (SSc). However, IgG anti-MMP-1 Ab levels were comparable among the 3 LSc subgroups: morphea, linear scleroderma, and generalized morphea. When absorbance values higher than the mean + 2S.D. of normal controls were considered positive, IgG or IgM anti-MMP-1 Ab was found in 46% and 49% of total LSc patients and SSc patients, respectively. Anti-MMP-1 Ab was detected most frequently in morphea patients (60%), followed by linear scleroderma patients (47%) and then generalized morphea patients (25%). LSc patients positive for IgG anti-MMP-1 Ab had elevated levels of IgG anti-single-stranded DNA Ab, IgG anti-nucleosome Ab, and shorter disease duration relative to those negative. The presence of anti-MMP-1 Ab in LSc patients was confirmed by immunoblotting. IgG isolated from LSc patients\u27 sera positive for IgG anti-MMP-1 Ab by ELISA inhibited MMP-1 collagenase activity. Conclusion: These results suggest that anti-MMP-1 autoantibody is a novel autoantibody in LSc. c 2008 Japanese Society for Investigative Dermatology

Increasing levels of serum antioxidant status, total antioxidant power, in systemic sclerosis.

Oxidative stress is one of the important factors that contribute to tissue damage in systemic sclerosis (SSc). Since the physiological response to oxidative stress is regulated by multiple antioxidant systems, it is important to measure quantitatively the total antioxidant capacity in the biological specimens. To determine the clinical significance of total antioxidant power (TAP) in SSc, we investigated the prevalence and clinical correlation of serum TAP levels in SSc patients. Serum TAP levels were examined in 49 patients with SSc by colorimetric microplate assay. The assay measures the total abilities for reducing Cu++ into Cu+. Clinical evaluation including medical history, physical examination, and laboratory tests were conducted for all SSc patients. Serum TAP levels were significantly elevated in SSc patients compared to normal controls (p < 0.01). When values higher than the mean + 2SD of the control serum samples were considered to be elevated, TAP levels were elevated in 24% of total SSc patients, with 26% of diffuse cutaneous SSc patients and 23% of limited cutaneous SSc patients. Serum TAP levels were correlated positively with C-reacting protein (r = 0.35, p ≤ 0.05). However, no other significant correlation was observed between serum TAP levels and clinical features in SSc patients. These results suggested that oxidative stress is enhanced in SSc patients, and serum TAP levels increase as an indicator of the global response to oxidative stress