Complement Diagnostics: Concepts, Indications, and Practical Guidelines

Aberrations in the complement system have been shown to be direct or indirect pathophysiological mechanisms in a number of diseases and pathological conditions such as autoimmune disease, infections, cancer, allogeneic and xenogeneic transplantation, and inflammation. Complement analyses have been performed on these conditions in both prospective and retrospective studies and significant differences have been found between groups of patients, but in many diseases, it has not been possible to make predictions for individual patients because of the lack of sensitivity and specificity of many of the assays used. The basic indications for serological diagnostic complement analysis today may be divided into three major categories: (a) acquired and inherited complement deficiencies; (b) disorders with complement activation; (c) inherited and acquired C1INH deficiencies. Here, we summarize indications, techniques, and interpretations for basic complement analyses and present an algorithm, which we follow in our routine laboratory

Complement Diagnostics: Concepts, Indications, and Practical Guidelines

Aberrations in the complement system have been shown to be direct or indirect pathophysiological mechanisms in a number of diseases and pathological conditions such as autoimmune disease, infections, cancer, allogeneic and xenogeneic transplantation, and inflammation. Complement analyses have been performed on these conditions in both prospective and retrospective studies and significant differences have been found between groups of patients, but in many diseases, it has not been possible to make predictions for individual patients because of the lack of sensitivity and specificity of many of the assays used. The basic indications for serological diagnostic complement analysis today may be divided into three major categories: (a) acquired and inherited complement deficiencies; (b) disorders with complement activation; (c) inherited and acquired C1INH deficiencies. Here, we summarize indications, techniques, and interpretations for basic complement analyses and present an algorithm, which we follow in our routine laboratory

The Swedish version of OMAS is a reliable and valid outcome measure for patients with ankle fractures

BACKGROUND: The aim of this study was to evaluate the test-retest reliability and the validity of the self-reported questionnaire Olerud-Molander Ankle Score (OMAS) in subjects after an ankle fracture. METHODS: When evaluating the test-retest reliability of the OMAS, 42 subjects surgically treated due to an ankle fracture participated 12 months after injury. OMAS was completed by the patients on two occasions at one to two weeks’ interval. Concurrent criterion validity was evaluated using the five subscales of the Foot and Ankle Outcome Score (FAOS) and global self-rating function (GSRF), which is a five-grade Likert scale with the alternatives: “very good”, “good”, “fair”, “poor”, “very poor”. Forty-six patients participated in the validation against FAOS, and for GSRF 105 patients participated at 6 months and 99 at 12 months. Uni-, bi- and trimalleolar fractures were all included and both non-rigid and rigid surgical techniques were used. All fractures healed without complications. Before analysis of the results the five groups according to GSRF were reduced to three: “good”, “fair” and “poor”. Test-retest reliability was assessed using Spearman’s rank correlation, the intraclass correlation coefficient (ICC), the standard error of measurement (SEM and SEM%) and the smallest real difference (SRD and SRD%). The Cronbach’s alpha score and validity versus FAOS was assessed using Spearman’s rank correlation and validity versus GSRF using the Kruskal-Wallis Test and the Mann–Whitney U-Test as ad hoc analyses. RESULTS: The test-retest reliability correlation coefficient obtained was rho = 0.95 and ICC = 0.94. The SEM was 4.4 points and SEM% 5.8% and should be interpreted as the smallest change that indicates a real change of clinical interest for a group of subjects. The SRD was 12 points and SRD% 15.8% and should be interpreted as the smallest change that indicates a real change of clinical interest for a single subject. The correlation coefficients versus the five subscales of FAOS ranged from rho = 0.80 to 0.86. There were significant differences between GSRF groups “good”, “fair” and “poor” (p < 0.001) at both the six-month and the 12-month follow-up. The internal consistency for the OMAS was 0.76. The effect size between results from 6-month and 12-month follow-up turned out be 0.44 and should be considered as medium. CONCLUSION: The results showed that the test-retest reliability of the Swedish version of OMAS was very high in subjects after an ankle fracture and the standard error of measurement was low. Furthermore the OMAS was found to be valid using both the five subscales of FAOS and the GSRF. The OMAS can thus be used as an outcome measure after an ankle fracture

Analysis of binding sites on complement factor I using artificial N-linked glycosylation.

Factor I (FI) is a serine protease that inhibits all complement pathways by degrading activated complement components C3b and C4b. FI functions only in the presence of several cofactors such as factor H, C4b-binding protein, complement receptor 1 and membrane cofactor protein. FI is composed of two chains linked by a disulphide bridge; the light chain comprises only the serine protease (SP) domain, while the heavy chain contains FI membrane attack complex domain (FIMAC), CD5 domain, low-density lipoprotein receptor 1 (LDLr1) and LDLr2 domains. To better understand how FI inhibits complement, we used homology-based 3D models of FI domains in an attempt to identify potential protein-protein interaction sites. Specific amino acids were then mutated to yield 20 recombinant mutants of FI carrying additional surface exposed N-glycosylation sites that were expected to sterically hinder interactions. The Michaelis constant (Km) of all FI mutants toward a small substrate was not increased. We found that many mutations in the FIMAC and SP domains nearly abolished ability of FI to degrade C4b and C3b in the fluid phase and on the surface, irrespectively of the cofactor used. In the other hand only few alterations in the CD5 and LDLr1/2 domains impaired this activity. In conclusion, all analyzed cofactors form similar trimolecular complexes with FI and C3b/C4b, and the accessibility of FIMAC and SP domains is crucial for the function of FI

Hemocompatibility of Nanotitania-Nanocellulose Hybrid Materials

In order to develop a new type of improved wound dressing, we combined the wound healing properties of nanotitania with the advantageous dressing properties of nanocellulose to create three different hybrid materials. The hemocompatibility of the synthesized hybrid materials was evaluated in an in vitro human whole blood model. To our knowledge, this is the first study of the molecular interaction between hybrid nanotitania and blood proteins. Two of the hybrid materials prepared with 3 nm colloidal titania and 10 nm hydrothermally synthesized titania induced strong coagulation and platelet activation but negligible complement activation. Hence, they have great potential as a new dressing for promoting wound healing. Unlike the other two, the third hybrid material using molecular ammonium oxo-lactato titanate as a titania source inhibited platelet consumption, TAT generation, and complement activation, apparently via lowered pH at the surface interface. It is therefore suitable for applications where a passivating surface is desired, such as drug delivery systems and extracorporeal circuits. This opens the possibility for a tailored blood response through the surface functionalization of titania

Результаты паратиреоидной аллотрансплантации

АЛЛОТРАНСПЛАНТАЦИЯГИПОПАРАТИРЕОЗИММУНОСУПРЕССИЯПАРАЩИТОВИДНЫЕ ЖЕЛЕЗЫ /хирТКАНЕВАЯ ТЕРАПИ