Fundamental role of C1q in autoimmunity and inflammation

C1q, historically viewed as the initiating component of the classical complement pathway, also exhibits a variety of complement-independent activities in both innate and acquired immunity. Recent studies focusing on C1q\u27s suppressive role in the immune system have provided new insight into how abnormal C1q expression and bioactivity may contribute to autoimmunity. In particular, molecular networks involving C1q interactions with cell surface receptors and other ligands are emerging as mechanisms involved in C1q\u27s modulation of immunity. Here, we discuss the role of C1q in controlling immune cell function, including recently elucidated mechanisms of action, and suggest how these processes are critical for maintaining tissue homeostasis under steady-state conditions and in preventing autoimmunity

Orthostatic hypotension: clinical review and case study

Transient loss of consciousness (TLOC) accounts for 3% of all attendance in emergency departments within the UK. More than 90% of TLOC presentations are due to epileptic seizures, psychogenic seizures or syncope. However, in England and Wales in 2002, it was estimated that 92000 patients were incorrectly diagnosed with epilepsy, at an additional annual cost to the NHS of up to £189 million. This article will reflect on the case study of a 54-year-old female patient who presented with a possible TLOC, and had a background of long-term depression. Differential diagnoses will be discussed, but the article will focus on orthostatic hypotension. Being diagnosed with this condition is independently associated with an increased risk of all-cause mortality. Causes of orthostatic hypotension and the pathophysiology behind the condition will be discussed, highlighting the importance of obtaining an accurate clinical history. This is extremely pertinent if a patient collapses in an NHS setting and this is witnessed by nurses because they can contribute to the history of the type of collapse, to aid diagnosis and correct treatment. In addition, nurses have a valuable role to play in highlighting polypharmacy to doctors, and non-medical prescribers, as a contributing factor to orthostatic hypotension is polypharmacy. It is therefore important to accurately distinguish TLOC aetiology, not only to provide appropriate management, but to also identify patients at risk of morbidity/mortality related to underlying disease.N/

Induction chemotherapy followed by chemoradiotherapy versus chemoradiotherapy alone as neoadjuvant treatment for locally recurrent rectal cancer: study protocol of a multicentre, open-label, parallel-arms, randomized controlled study (PelvEx II)

Background A resection with clear margins (R0 resection) is the most important prognostic factor in patients with locally recurrent rectal cancer (LRRC). However, this is achieved in only 60 per cent of patients. The aim of this study is to investigate whether the addition of induction chemotherapy to neoadjuvant chemo(re)irradiation improves the R0 resection rate in LRRC. Methods This multicentre, international, open-label, phase III, parallel-arms study will enrol 364 patients with resectable LRRC after previous partial or total mesorectal resection without synchronous distant metastases or recent chemo- and/or radiotherapy treatment. Patients will be randomized to receive either induction chemotherapy (three 3-week cycles of CAPOX (capecitabine, oxaliplatin), four 2-week cycles of FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) or FOLFORI (5-fluorouracil, leucovorin, irinotecan)) followed by neoadjuvant chemoradiotherapy and surgery (experimental arm) or neoadjuvant chemoradiotherapy and surgery alone (control arm). Tumours will be restaged using MRI and, in the experimental arm, a further cycle of CAPOX or two cycles of FOLFOX/FOLFIRI will be administered before chemoradiotherapy in case of stable or responsive disease. The radiotherapy dose will be 25 × 2.0 Gy or 28 × 1.8 Gy in radiotherapy-naive patients, and 15 × 2.0 Gy in previously irradiated patients. The concomitant chemotherapy agent will be capecitabine administered twice daily at a dose of 825 mg/m2 on radiotherapy days. The primary endpoint of the study is the R0 resection rate. Secondary endpoints are long-term oncological outcomes, radiological and pathological response, toxicity, postoperative complications, costs, and quality of life. Discussion This trial protocol describes the PelvEx II study. PelvEx II, designed as a multicentre, open-label, phase III, parallel-arms study, is the first randomized study to compare induction chemotherapy followed by neoadjuvant chemo(re)irradiation and surgery with neoadjuvant chemo(re)irradiation and surgery alone in patients with locally recurrent rectal cancer, with the aim of improving the number of R0 resections

SERUM LAIR-2 IS INCREASED IN AUTOIMMUNE THYROID DISEASES

Leukocyte-associated Ig-like receptor (LAIR) is a small family-receptor able to inhibit immune cell function via collagen binding. It exists as both membrane-bound and soluble forms. LAIR-1 functions as an inhibitory receptor on natural killer cells, T lymphocytes and monocytes. In addition to LAIR-1, the human genome encodes LAIR-2, a soluble homolog. Several studies have focused on LAIR-1, whereas few investigations concentrate on the expression and function of LAIR-2. We demonstrate the presence of high LAIR-2 levels in 74/80 sera from patients with autoimmune thyroid diseases (both Graves\u2019 disease and autoimmune thyroiditis). LAIR-2 levels seemed not to be related to specific clinical manifestations, such as thyroid functions (hypo- or hyperthyroidism), or specific clinical features (such as ophtalmopathy). In addition, serum LAIR-2 is able, in vitro, to bind its natural ligand, collagen. Since LAIR-2 has been found to have higher affinity for collagens than LAIR-1 did, we hypothesize a potential regulating capability of serum LAIR-2 in finelly regulating the inhibitory capability of LAIR-1