Smoking in Systemic Sclerosis: a Longitudinal European Scleroderma Trials and Research Group Study

Data on the role of tobacco exposure in systemic sclerosis (SSc) severity and progression are scarce. We aimed to assess the effects of smoking on the evolution of pulmonary and skin manifestations in the EUSTAR database

Impact of fixed orthodontic appliances on blood count and high-sensitivity C-reactive protein levels: A prospective cohort study.

INTRODUCTION The aim was to elucidate the magnitude of alterations in systemic blood counts in healthy patients during the first 14 days after fixed orthodontic appliance placement. METHODS This prospective cohort study consecutively included 35 White Caucasian patients starting orthodontic treatment with fixed appliances. The mean age was 24.48 ± 6.68 years. All patients were physically and periodontally healthy. Blood samples were collected at 3 time points: (1) baseline (exactly before the placement of appliances), (2) 5 days after bonding, and (3) 14 days after baseline. Whole blood and erythrocyte sedimentation rates were analyzed in automated hematology and erythrocyte sedimentation rate analyzer. Serum high-sensitivity C-reactive protein levels were measured by the nephelometric method. Standardized sample handling and patient preparation procedures were adopted to reduce preanalytical variability. RESULTS A total of 105 samples were analyzed. All clinical and orthodontic procedures were performed without complications or side effects during the study period. All laboratory procedures were performed per protocol. Significantly lower white blood cell counts were detected 5 days after bracket bonding, compared with baseline (P <0.05). Hemoglobin levels were lower at 14 days than baseline (P <0.05). No other significant shifts or alteration patterns were observed over time. CONCLUSIONS Orthodontic fixed appliances led to a limited and transient change in white blood cell counts and hemoglobin levels during the first days after bracket placement. The fluctuation of high-sensitivity C-reactive protein levels was not significant, demonstrating a lack of association between systemic inflammation and orthodontic treatment

Registry Evaluation of Digital Ulcers in Systemic Sclerosis

Digital ulcers are a very frequent complication of systemic sclerosis affecting about half of the SSc patients, and about 75% of the affected patients have their first DU episode within 5 years from their first non-Raynaud symptom. The lack of adequate classification criteria as well as the lack of knowledge of the development of DU have contributed to the opening of specific registries to better understand the natural history of these lesions. For these reason, specific disease registries play a fundamental role in this field of research. Thanks to the systematic collection of data and their subsequent analysis and comparison between different cohorts, it is possible to improve understanding of the underlying trigger mechanisms of DU development and to determine temporal trends. In the future, the development of recommendations for the management of DU remains of pivotal importance to prevent DU development and obtain rapid healing as well as reduction of pain and disability

The Role of Proteoglycans in Contributing to Placental Thrombosis and Fetal Growth Restriction

Fetal growth restriction is an important pregnancy complication that has major consequences for the fetus and neonate as well as an increased risk of long-term morbidity extending into adulthood. The precise aetiology of most cases of fetal growth restriction is unknown although placental thrombosis is a common feature in many of these cases. This paper will outline the potential role of proteoglycans in contributing to placental thrombosis and fetal growth restriction

PHENOTYPIC ANALYSIS OF MICE DEFICIENT FOR Ly6C1/Ly6C2

Ly6C comprises two homologous components of Ly6C1 and Ly6C2, and the expression of either of the Ly6C molecules defines unique functional subsets of monocytes. Ly6C is also expressed by other immune cell types, including Aire-expressing medullary thymic epithelial cells. Because the role of Ly6C expression in determining the functional subsets remains unclear, we generated mice deficient for both Ly6C1 and Ly6C2 with CRISPR-Cas9–mediated deletion. Mice deficient for Ly6C1/Ly6C2 showed no major alterations in the subsets and function of monocyte and other immune cells, including the cells involved in the dextran sulfate sodium salt–induced colitis model. By generating the mice deficient for Ly6C1 alone, we have also investigated the expression pattern of Ly6C1 and Ly6C2 in immune cells. Except for medullary thymic epithelial cells and CD4 single-positive T cells, immune cells predominantly expressed Ly6C2. Thus, despite the importance as a marker with a unique differential expression pattern, the Ly6C molecules have no major impact on determining the functional subsets and maintaining immune homeostasis

Collagenous Colitis and Spondylarthropathy

Collagenous colitis is a recent cause of chronic diarrhea. Cooccurrence with spondylarthropathy is rare. We describe two cases: one man and one woman of 33 and 20 years old were suffering from spondylarthropathy. They then developed collagenous colitis, 4 and 14 years after the onset of spondylarthropathy. The diagnosis was based on histological features. A sicca syndrome and vitiligo were observed with the female case. The presence of colitis leads to therapeutic problems. This association suggests a systemic kind of rheumatic disease of collagenous colitis

Neutrophilic Cell-Free Exudate Induces Antinociception Mediate by the Protein S100A9

Calcium-binding protein S100A9 (MRP-14) induces antinociceptive effect in an experimental model of painful sensibility and participates of antinociception observed during neutrophilic peritonitis induced by glycogen or carrageenan in mice. In this study, the direct antinociceptive role of the protein S100A9 in neutrophilic cell-free exudates obtained of mice injected with glycogen was investigated. Mice were intraperitoneally injected with a glycogen solution, and after 4, 8, 24, and 48 hours, either the pattern of cell migration of the peritoneal exudate or the nociceptive response of animals was evaluated. The glycogen-induced neutrophilic peritonitis evoked antinociception 4 and 8 hours after inoculation of the irritant. Peritoneal cell-free exudates, collected in different times after the irritant injection, were transferred to naive animals which were submitted to the nociceptive test. The transference of exudates also induced antinociceptive effect, and neutralization of S100A9 activity by anti-S100A9 monoclonal antibody totally reverted this response. This effect was not observed when experiments were made 24 or 48 hours after glycogen injection. These results clearly indicate that S100A9 is secreted during glycogen-induced neutrophilic peritonitis, and that this protein is responsible by antinociception observed in the initial phase of inflammatory reaction. Thus, these data reinforce the hypothesis that the calcium-binding protein S100A9 participates of the endogenous control of inflammatory pain

Role of Bone Marrow-Derived Monocytes/Macrophages in the Repair of Mucosal Damage Caused by Irradiation and/or Anticancer Drugs in Colitis Model

Mucosal damage is a common side effect of many cancer treatments, especially radiotherapy and intensive chemotherapy, which often induce bone marrow (BM) suppression. We observed that acetic acid- (AA-) induced mucosal damage in the colon of mice was worsened by simultaneous treatment with irradiation or 5-FU. However, irradiation 14 days prior to the AA treatment augmented the recovery from mucosal damage, suggesting that the recovery from BM suppression had an advantageous effect on the mucosal repair. In addition, BM transplantation also augmented the recovery from AA-induced mucosal damage. We further confirmed that transplanted BM-derived cells, particularly F4/80+Gr1+ “inflammatory” monocytes (Subset 1), accumulated in the damaged mucosal area in the early healing phase, and both of Subset 1 and F4/80+Gr1− “resident” monocytes (Subset 2) accumulated in this area in later phases. Our results suggest that monocytes/macrophages contribute to the mucosal recovery and regeneration following mucosal damage by anticancer drug therapy

Adaptive Immune Response to Model Antigens Is Impaired in Murine Leukocyte-Adhesion Deficiency-1 Revealing Elevated Activation Thresholds In Vivo

Absence of β2 integrins (CD11/CD18) leads to leukocyte-adhesion deficiency-1 (LAD1), a rare primary immunodeficiency syndrome. Although extensive in vitro work has established an essential function of β2 integrins in adhesive and signaling properties for cells of the innate and adaptive immune system, their respective participation in an altered adaptive immunity in LAD1 patients are complex and only partly understood in vivo. Therefore, we investigated adaptive immune responses towards different T-dependent antigens in a murine LAD1 model of β2 integrin-deficiency (CD18−/−). CD18−/− mice generated only weak IgG responses after immunization with tetanus toxoid (TT). In contrast, robust hapten- and protein-specific immune responses were observed after immunization with highly haptenated antigens such as (4-hydroxy-3-nitrophenyl)21 acetyl chicken γ globulin (NP21-CG), even though regularly structured germinal centers with specificity for the defined antigens/haptens in CD18−/− mice remained absent. However, a decrease in the hapten/protein ratio lowered the efficacy of immune responses in CD18−/− mice, whereas a mere reduction of the antigen dose was less crucial. Importantly, haptenation of TT with NP (NP-TT) efficiently restored a robust IgG response also to TT. Our findings may stimulate further studies on a modification of vaccination strategies using highly haptenated antigens in individuals suffering from LAD1

Toll-Like Receptor 4 Activation in Cancer Progression and Therapy

Cancer immunotherapy has been the focus of intense research since the late 19th century when Coley observed that bacterial components can contribute to cancer regression by eliciting an antitumor immune response. Successful activation and maturation of tumor-specific immune cells is now known to be mediated by bacterial endotoxin, which activates Toll-like receptor 4 (TLR4). TLR4 is expressed on a variety of immune as well as tumor cells, but its activation can have opposing effects. While TLR4 activation can promote antitumor immunity, it can also result in increased tumor growth and immunosuppression. Nevertheless, TLR4 engagement by endotoxin as well as by endogenous ligands represents notable contribution to the outcome of different cancer treatments, such as radiation or chemotherapy. Further research of the role and mechanisms of TLR4 activation in cancer may provide novel antitumor vaccine adjuvants as well as TLR4 inhibitors that could prevent inflammation-induced carcinogenesis