CD28 signals the differential control of regulatory T cells and effector T cells

One possible means of driving antigen‐specific immune suppression is to expand or induce antigen‐specific FoxP3‐expressing Treg cells. One way of activating and expanding these specialized cells, both in vitro and in vivo, is by strong costimulation via CD28 with an agonistic anti‐CD28 monoclonal antibody, called anti‐CD28 superagonist (CD28SA). However, CD28SA also strongly activates conventional T (Tconv) cells to secrete proinflammatory cytokines and, under certain conditions, causes serious cytokine release syndrome. In this issue of European Journal of Immunology, Tabares et al. [Eur. J. Immunol. 2014. 44: 1225–1236] address how CD28SA can be used for the differential control of human Treg and Tconv cells to suppress immune responses without serious adverse effects. They show that, depending on the dose of the antibody or by comedication of cortico‐steroid, the selective expansion of Treg cells can be achieved without significantly activating Tconv cells to produce inflammatory cytokines. This difference in CD28 signal sensitivity between the two populations can be exploited for better control of immune responses.     

Isolation and characterization of 25 polymorphic microsatellites of the large Japanese wood mouse (Apodemus speciosus)

The large Japanese wood mouse (Apodemus speciosus) is common, but endemic to Japan, and its population structure was affected by habitat fragmentation because of urbanization. It suggested that the species might be one of the important models for the conservation of ecosystems and biodiversity affected by humans, including the effect of radioactive discharge caused by nuclear power plant accidents at Fukushima. We developed and characterized 25 novel polymorphic microsatellite markers from the next-generation sequencing data in an effort to provide an effective tool for genetic studies on this species. In 8 individuals from Aomori, Japan, the number of alleles and expected heterozygosities ranged from 5 to 13 and from 0.795 to 0.991, respectively, suggesting the availability of these markers for genetic studies in this species.     

Prognosis of pneumocystis pneumonia complicated in patients with rheumatoid arthritis (RA) and non-RA rheumatic diseases

Clinical presentation of pneumocystis pneumonia (PCP) during immunosuppressive therapy for rheumatic diseases was compared between patients with rheumatoid arthritis (RA; n = 7) and those without RA (non-RA; n = 12) based on a chart review. Both RA and non-RA patients with PCP were treated with methotrexate (n = 7) combined with steroids (n = 6) and/or biologics (n = 4). RA-PCP patients were found to have a higher mortality rate than non-RA-PCP patients (3/7 vs. 0/12, respectively; p?=?0.036) due to a later exacerbation of interstitial pneumonia and a higher presentation rate of diffuse pulmonary lesions (4/7 vs. 1/12, respectively; p?=?0.036) despite lower mean levels of serum beta-D: -glucan (314?±?214 vs. 1139?±?1114?pg/ml, respectively; p?=?0.02) that suggested a lower burden of Pneumocystis jirovecii. In conclusion, PCP in RA patients with existing pulmonary lesions may trigger subsequent progression to lethal interstitial pneumonia.     

Omental patch repair effectively treats perforated marginal ulcer following Roux-en-Y gastric bypass

Background

Marginal ulcer formation remains a significant complication of Roux-en-Y gastric bypass (RYGB). Up to 1 % of all RYGB patients will develop free perforation of a marginal ulcer. Classically, this complication has required anastomotic revision; however, this approach is associated with significant morbidity. Several small series have suggested that omental patch repair may be effective. The aim of this study was to examine the management of perforated marginal ulcers following RYGB.

Methods

All patients who underwent operative intervention for perforated ulcers between 2003 and 2011 were reviewed. Those with a history of RYGB with perforation of a marginal ulcer were included in the analysis. Data collected included operative approach, operative time, blood loss, length of hospital stay, complications, smoking history, and steroid or NSAID use.

Results

From January 2003 to December 2011, a total of 1,760 patients underwent RYGB at our institution. Eighteen (0.85 %) developed perforation of a marginal ulcer. Three patients’ original procedure was performed at another institution. Eight patients (44 %) had at least one risk factor for ulcer formation. Treatment included omental patch repair (laparoscopic, n = 7; open, n = 9) or anastomotic revision (n = 2). Compared to anastomotic revision, omental patch repair had shorter OR time (101 ± 57 vs. 138 ± 2 min), decreased estimated blood loss (70 ± 72 vs. 250 ± 71 mL), and shorter total length of stay (5.6 ± 1.4 vs. 11.0 ± 5.7 days).

Conclusions

Perforated marginal ulcer represents a significant complication of RYGB. Patients should be educated to reduce risk factors for perforation, as prolonged proton pump inhibitor therapy may not prevent this complication in a patient with even just one risk factor. In our sample population we found laparoscopic or open omental patch repair to be a safe and effective treatment for this condition and it was associated with decreased operative time, blood loss, and length of stay.