The axis of complement C1 and nucleolus in antinuclear autoimmunity.

Antinuclear autoantibodies (ANA) are heterogeneous self-reactive antibodies that target the chromatin network, the speckled, the nucleoli, and other nuclear regions. The immunological aberration for ANA production remains partially understood, but ANA are known to be pathogenic, especially, in systemic lupus erythematosus (SLE). Most SLE patients exhibit a highly polygenic disease involving multiple organs, but in rare complement C1q, C1r, or C1s deficiencies, the disease can become largely monogenic. Increasing evidence point to intrinsic autoimmunogenicity of the nuclei. Necrotic cells release fragmented chromatins as nucleosomes and the alarmin HMGB1 is associated with the nucleosomes to activate TLRs and confer anti-chromatin autoimmunogenecity. In speckled regions, the major ANA targets Sm/RNP and SSA/Ro contain snRNAs that confer autoimmunogenecity to Sm/RNP and SSA/Ro antigens. Recently, three GAR/RGG-containing alarmins have been identified in the nucleolus that helps explain its high autoimmunogenicity. Interestingly, C1q binds to the nucleoli exposed by necrotic cells to cause protease C1r and C1s activation. C1s cleaves HMGB1 to inactive its alarmin activity. C1 proteases also degrade many nucleolar autoantigens including nucleolin, a major GAR/RGG-containing autoantigen and alarmin. It appears that the different nuclear regions are intrinsically autoimmunogenic by containing autoantigens and alarmins. However, the extracellular complement C1 complex function to dampen nuclear autoimmunogenecity by degrading these nuclear proteins.

Influence of glycan structure on the colonization of Streptococcus pneumoniae on human respiratory epithelial cells.

Virtually all living cells are encased in glycans. They perform key cellular functions such as immunomodulation and cell-cell recognition. Yet, how their composition and configuration affect their functions remains enigmatic. Here, we constructed isogenic capsule-switch mutants harboring 84 types of capsular polysaccharides (CPSs) in Streptococcus pneumoniae. This collection enables us to systematically measure the affinity of structurally related CPSs to primary human nasal and bronchial epithelial cells. Contrary to the paradigm, the surface charge does not appreciably affect epithelial cell binding. Factors that affect adhesion to respiratory cells include the number of rhamnose residues and the presence of human-like glycomotifs in CPS. Besides, pneumococcal colonization stimulated the production of interleukin 6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF), and monocyte chemoattractantprotein-1 (MCP-1) in nasal epithelial cells, which also appears to be dependent on the serotype. Together, our results reveal glycomotifs of surface polysaccharides that are likely to be important for colonization and survival in the human airway.

A Comprehensive Analysis of Traumatic Rib Fractures in an Acute General Hospital in Singapore.

BACKGROUND: Rib fractures are common sequelae after blunt chest wall trauma. They can occur in isolation or association with life-threatening injuries to the head, thorax, and abdomen and may be complicated by hemothorax, pneumothorax, or lung contusions. Contiguous rib fractures can result in flail chest, which is associated with increased morbidity and mortality. This study aims to compare the risk factors, treatment modalities, and outcomes between patients with flail chest and nonflail chest postblunt trauma. PATIENTS AND METHODS: Data were retrospectively collected from all patients admitted with rib fractures from January 2016 to December 2016 to the Department of General Surgery, Khoo Teck Puat Hospital, Singapore. The outcomes identified were mortality, pain scores on injury day 1, 3, 5, and 7, injury severity score, duration of mechanical ventilation, worst partial pressure arterial oxygen/fraction of inspired oxygen (PaO2/FiO2) ratio, length of intensive care unit (ICU) stay, and pulmonary complications. RESULTS: Motor vehicle accident was the most common cause of rib fractures (63.1%, n = 123). Patients with flail chest had more associated pneumothorax (53.8% vs. 35.2%) and lung contusions (53.8% vs. 30.2%) compared to those without flail chest and underwent more investigations such as inpatient-computed tomography scans (76.9% vs. 59.3%), interventions such as chest tube insertion (61.5% vs. 19.8%), and ICU admission (46.1 vs. 13.7%). Patients also had higher pain scores, used more analgesic modalities, and had increased inpatient mortality (30.8% vs. 4.4%). CONCLUSION: Flail chest is associated with higher morbidity and mortality. Proactive management from a multidisciplinary team such as identification of high-risk patients in particular patients with flail chest, early admission to critical care, and protocols including multimodal pain management, respiratory support, and rehabilitation should be instituted.