THU0312 Microcirculation Comparative Study in Fibromyalgia Patients with and without Raynaud's Phenomenon: Table 1.

Abstract

Background Previous studies demonstrated functional and morphological microcirculatory abnormalities that may be relevant to the pathophysiology and clinical manifestations of fibromyalgia (FM). Objectives To ascertain and compare capillary morphology of FM patients with and without Raynaud's phenomenon (RP) using nailfold videocapillaroscopy (NVC). Methods Patients fulfilling the 2010 American College of Rheumatology Diagnostic Criteria for FM were allocated in 2 groups according to the presence or absence of RP (RP+ or RP-, respectively). All patients with secondary causes of RP other than FM were excluded. One blinded operator performed all the NVC using a 200x amplification digital microscope and analytical software. Capillary parameters evaluated in fingers II-V of both hands included: tortuosity, apex enlargement, branch enlargement, microhemorrhages, giant capillaries, capillary density, capillary branching and architectural derangements. Each parameter was rated 0-3 (0= no changes; 1= <33% abnormalities; 2=33-66% abnormalities; 3= >66% abnormalities) and the mean scores were calculated. The association of RP with the capillary parameters was assessed using multivariate linear regression adjusted for age, FM duration and occupation. Results Twenty FM patients were enrolled, 10 in each group, however 2 patients RP+ were excluded due to thyroid disease. Included patients were all female, had a mean age of 50.4 years and a mean duration of disease of 12.8 years. In both RP+ and RP- groups, the most frequently found abnormalities were minor dysmorphies, namely tortuosities, apex enlargement and branch enlargement. However, scoring of these parameters showed no significant difference between the 2 groups. More than half of RP+ and RP- patients presented slight focal decreases in capillary density, once again with no difference between groups. The only giant capillaries were found in a RP+ patient with an “early scleroderma pattern” as proposed by Cutolo et al. Hemorrhages were scarce and had a traumatic appearance, except in the previously mentioned patient. Interestingly, RP associated negatively with the capillary branching score. Table 1 summarizes the results. Table 1. Microcirculatory parameters assessed in fibromyalgia patients with and without Raynaud's phenomenon Parameters RP+, n=8 RP−, n=10 Adjusted p-value n (%) Score, median (IQR) n (%) Score, median (IQR) Tortuosity 8 (100) 1.17 (0.66) 10 (100) 1.25 (0.53) 0.99 Apex enlargement 7 (87.5) 0.31 (0.50) 10 (100) 0.14 (0.06) 0.26 Branch enlargement 7 (87.5) 0.13 (0.33) 10 (100) 0.03 (0.06) 0.06 Microhemorrhages 2 (25) 0 (0.06) 2 (20) 0 (0) 0.20 Giant capillaries 1 (12.5) 0 (0) 0 (0) 0 (0) 0.24 Capillary density 5 (62.5) 0.03 (0.09) 6 (60) 0.08 (0.19) 0.98 Capillary branching 3 (37.5) 0 (0.03) 5 (50) 0.03 (0.13) 0.04 Architectural derangements 2 (25) 0 (0.08) 3 (30) 0 (0.03) 0.27 IQR, interquartile range; RP, Raynaud's phenomenon. Conclusions No association was established between RP and microcirculatory abnormali...

Conformational Analysis of Large and Highly Disulfide-Stabilized Proteins by Integrating Online Electrochemical Reduction into an Optimized H/D Exchange Mass Spectrometry Workflow

“…NGF is a small, 13 kDa, protein involved in the correct development of both the central and peripheral nervous system . The structure of NGF is dominated by three pairs of antiparallel β-strands, and it contains three intersecting disulfide bonds forming a so-called cysteine knot that tightly binds the protein together, thus making it very resistant to reduction and enzymatic digestion. − On the other hand, therapeutic IgG 1 -antibodies are large, 150 kDa, multichain molecules, which are used to treat a huge variety of diseases from cancer to anti-immune disorders. , IgG 1 -antibodies consist of two light and two heavy chains, connected by four interchain disulfide bonds. Furthermore, two and four intrachain disulfide bonds are situated on the light and heavy chain, respectively …”

“…37−39 On the other hand, therapeutic IgG 1 -antibodies are large, 150 kDa, multichain molecules, which are used to treat a huge variety of diseases from cancer to anti-immune disorders. 40,41 chain disulfide bonds are situated on the light and heavy chain, respectively. 42 To enable an unbiased comparison to a classical HDX-MS workflow employing chemical reduction, we systematically screened conditions for optimal chemical reduction and digestion of NGF using 26 different quench conditions.…”