C-Reactive Protein (CRP) and Autoimmune Disease: Facts and Conjectures

C-reactive protein (CRP) is a blood component comprised of five identical subunits with a combined molecular mass of 110 kDa; in the presence of Ca++ it binds phosphocholine (PC) with high affinity. Ligand-bound CRP activates complement and the protein reportedly binds various Fc receptors. Coincident with a now decade-long resurgence in clinical interest in associations of CRP with disease, our laboratory has been investigating the biology of CRP in vivo using human CRP transgenic mice (CRPtg). At that time we confirmed that CRP affects a host defense function mediated at least in part through the elimination of pathogens. Less appreciated and not as well understood as CRP's ability to bind antigen and aid in the elimination of microbes, is its known ability to bind autoantigens and presumed capacity to promote clearance of apoptotic cells. These latter properties of CRP have long been suspected to contribute to homeostasis and to autoimmune disease. In this article we review and update the evidence generated in CRPtg by our group and in vitro by others' that indicates CRP is more than just an antimicrobial molecule and convenient marker of inflammation - rather, it protects against autoimmunity. A mechanistic hypothesis is presented to account for this cause-and-effect relationship

Inhibition of Experimental Autoimmune Encephalomyelitis in Human C-Reactive Protein Transgenic Mice Is FcγRIIB Dependent

We showed earlier that experimental autoimmune encephalomyelitis (EAE) in human C-reactive protein (CRP) transgenic mice (CRPtg) has delayed onset and reduced severity compared to wild-type mice. Since human CRP is known to engage Fc receptors and Fc receptors are known to play a role in EAE in the mouse, we sought to determine if FcγRI, FcγRIIb, or FcγRIII was needed to manifest human CRP-mediated protection of CRPtg. We report here that in CRPtg lacking either of the two activating receptors, FcγRI and FcγRIII, the beneficial effects of human CRP are still observed. In contrast, if CRPtg lack expression of the inhibitory receptor FcγRIIB, then the beneficial effect of human CRP is abrogated. Also, subcutaneous administration of purified human CRP stalled progression of ongoing EAE in wild-type mice, but similar treatment failed to impede EAE progression in mice lacking FcγRIIB. The results reveal that a CRP → FcγRIIB axis is responsible for protection against EAE in the CRPtg model

Spectral domain optical coherence tomography in patients after successful management of postoperative endophthalmitis following cataract surgery by pars plana vitrectomy.

BACKGROUND: Acute severe postoperative endophthalmitis may lead to severe vision loss. The aim of this study was the analysis of macular microstructure imaged by spectral domain optical coherence tomography in patients after pars plana vitrectomy due to postcataract endophthalmitis. METHODS: A cross sectional study was carried out in 17 patients who had cataract surgery in both eyes and underwent unilateral pars plana vitrectomy due to postcataract endophthalmitis. Postoperative best corrected visual acuity was determined in both eyes. Evaluation of macular thickness, macular volume, peripapillary retinal nerve fiber layer thickness and choroidal thickness using enhanced depth imaging technique was performed by spectral domain optical coherence tomography. The measurements obtained in the operated eye were compared to the fellow eye by Wilcoxon matched pair test. Correlation test was performed by Spearman rank order. RESULTS: A mean postoperative best corrected visual acuity of 63 +/- 30 ETDRS letters versus 75 +/- 21 letters was achieved in the study and fellow eyes, respectively, after a mean of 5.3 +/- 4.5 months (p = 0.1). The mean macular thickness was 320.6 +/- 28.8 mum SD in the study eyes compared to 318.4 +/- 18.8 mum in the fellow eyes (p = 0.767). No differences were noted in macular volume (p = 0.97) and in peripapillary retinal nerve fiber layer thickness (p = 0.31). Choroidal thickness was significantly lower in the study eyes compared to the fellow eyes (p = 0.018). Epiretinal membrane was found in 7 eyes after endophthalmitis, while in the fellow eyes only in 3 cases (p = 0.13, Fisher's exact test). CONCLUSION: Choroidal thickness decreased significantly after endophthalmitis, but there was no functional correlation with the changes in choroidal microstructure. The development of epiretinal membranes may be associated with either vitrectomy or endophthalmitis in the history. Absence of other significant structural and morphological findings shows that successful treatment may guarantee good clinical results even in long term after this severe postoperative complication

The Great Escape: How Exoplanets and Smaller Bodies Desert Dying Stars

Mounting discoveries of extrasolar planets orbiting post-main sequence stars motivate studies aimed at understanding the fate of these planets. In the traditional "adiabatic" approximation, a secondary's eccentricity remains constant during stellar mass loss. Here, we remove this approximation, investigate the full two-body point-mass problem with isotropic mass loss, and illustrate the resulting dynamical evolution. The magnitude and duration of a star's mass loss combined with a secondary's initial orbital characteristics might provoke ejection, modest eccentricity pumping, or even circularisation of the orbit. We conclude that Oort clouds and wide-separation planets may be dynamically ejected from 1-7 Solar-mass parent stars during AGB evolution. The vast majority of planetary material which survives a supernova from a 7-20 Solar-mass progenitor will be dynamically ejected from the system, placing limits on the existence of first-generation pulsar planets. Planets around >20 Solar-mass black hole progenitors may easily survive or readily be ejected depending on the core collapse and superwind models applied. Material ejected during stellar evolution might contribute significantly to the free-floating planetary population.Comment: 23 pages, 16 figures, accepted for publication in MNRA

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362