Beta-2-glycoprotein specificity of human anti-phospholipid antibody resides on the light chain: a novel mechanism for acquisition of cross-reactivity by an autoantibody

We have recently shown that the anti-cardiolipin activity of human anti-phospholipid antibody UK4 (lambda) resides on its heavy chain. We now show that UK4 possesses strong reactivity to the plasma-protein beta2-Glycoprotein I (beta2-GPI) also. Utilizing chain shuffling experiments involving an unrelated anti-p185 antibody 4D5 (kappa) with no reactivity to beta2-GPI, we now demonstrate that both the constructs possessing the auto-antibody-derived light chain exhibited significant binding to beta2-GPI. However, the construct possessing UK4 heavy chain in association with 4D5 light chain, exhibited no anti-beta2-GPI activity. Furthermore, there was a low increase (approximately 10%) in the binding of UK4 to cardiolipin in the presence of beta2-GPI. The results demonstrate that anti-beta2-GPI activity resides on UK4 light chain and, importantly, this activity could be transferred to a novel antibody construct via the light chain alone. Computer-generated models of the three-dimensional structures of UK4 and its hybrids, suggest predominant interaction of UK4 light chain with domain IV of beta2-GPI. Molecular docking experiments highlight a number of potential sites on beta2-GPI for interaction of UK4 and indicate as to how beta2-GPI recognition may occur primarily via the autoantibody light chain. The study provides first demonstration of the occurrence of anti-phospholipid and anti-beta2-GPI activities separately on heavy and light chains of an autoantibody. The possible mechanisms that such antibodies may employ to recognise their antigens, are discussed.     

Curcumin,Quercetin, Catechins and Metabolic Diseases: The Role of Gut Microbiota

Polyphenols (PPs) are the naturally occurring bioactive components in fruits and vegetables, and they are the most abundant antioxidant in the human diet. Studies are suggesting that ingestion of PPs might be helpful to ameliorate metabolic syndromes that may contribute in the prevention of several chronic disorders like diabetes, obesity, hypertension, and colon cancer. PPs have structural diversity which impacts their bioavailability as they accumulate in the large intestine and are extensively metabolized through gut microbiota (GM). Intestinal microbiota transforms PPs into their metabolites to make them bioactive. Interestingly, not only GM act on PPs to metabolize them but PPs also modulate the composition of GM. Thus, change in GM from pathogenic to beneficial ones may be helpful to ameliorate gut health and associated diseases. However, to overcome the low bioavailability of PPs, various approaches have been developed to improve their solubility and transportation through the gut. In this review, we present evidence supporting the structural changes that occur after metabolic reactions in PPs (curcumin, quercetin, and catechins) and their effect on GM composition that leads to improving overall gut health and helping to ameliorate metabolic disorders.     

Self‐initiated use of topical cannabidiol oil for epidermolysis bullosa

Epidermolysis bullosa is a rare blistering skin disorder that is challenging to manage because skin fragility and repeated wound healing cause itching, pain, limited mobility, and recurrent infections. Cannabidiol, an active cannabinoid found in cannabis, is postulated to have antiinflammatory and analgesic effects. We report 3 cases of self‐initiated topical cannabidiol use in patients with epidermolysis bullosa in an observational study. One patient was weaned completely off oral opioid analgesics. All 3 reported faster wound healing, less blistering, and amelioration of pain with cannabidiol use. Although these results demonstrate promise, further randomized, double‐blind clinical trials are necessary to provide scientific evidence of our observed benefits of cannabidiol for the treatment of epidermolysis bullosa.     

Risk-reducing laparoscopic cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for low-grade appendiceal mucinous neoplasm: early outcomes and technique

Background

Low-grade appendiceal mucinous neoplasm (LAMN) is a precursor lesion of pseudomyxoma peritonei, which, if treated suboptimally, may later disseminate throughout the abdominal cavity. We previously demonstrated the role of cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) to reduce the dissemination risk. Here we describe the feasibility and safety of minimal access cytoreductive surgery (MACRS) and HIPEC as an alternative to the open approach.

Methods

We evaluated patients with LAMNs at risk of dissemination (known as LAMN II) who were referred to a national treatment centre between 2010 and 2012 and comparison is made between this group and patients undergoing open CRS and HIPEC for the same pathology over the same time period.

Results

Of the 39 patients with LAMN II, 10 patients were treated by MACRS and HIPEC and 7 were treated by an open approach. Among the MACRS procedures, there were no conversions to open surgery; median procedure length, median length of stay, and complication rates were similar between groups and there were no 30-day deaths. After 3- and 11-months median follow-up respectively, no patients have evidence of disease progression.

Conclusions

The present series demonstrates that MACRS and HIPEC is a feasible and safe alternative to the open procedure with the advantage of smaller abdominal wounds and comparable morbidity and inpatient stay. Longer follow-up is needed to assess the impact on disease progression.     

Rare case of breast tumor secondary to rectal adenocarcinoma

Primary breast cancer is the most common malignancy in women. Metastatic cancer to the breast is very rare. Colorectal cancers usually metastasize to the liver and the lung; other sites of metastasis from colon cancer are uncommon and are usually found in association with extensive liver and/or lung metastases. This is a report of a rare case of aggressive rectal cancer with metastasis to the breast without liver or lung metastases.