A prominent lack of IgG1-Fc fucosylation of platelet alloantibodies in pregnancy.

Immunoglobulin G (IgG) formed during pregnancy against human platelet antigens (HPAs) of the fetus mediates fetal or neonatal alloimmune thrombocytopenia (FNAIT). Because antibody titer or isotype does not strictly correlate with disease severity, we investigated by mass spectrometry variations in the glycosylation at Asn297 in the IgG Fc because the composition of this glycan can be highly variable, affecting binding to phagocyte IgG-Fc receptors (FcγR). We found markedly decreased levels of core fucosylation of anti-HPA-1a-specific IgG1 from FNAIT patients (n = 48), but not in total serum IgG1. Antibodies with a low amount of fucose displayed higher binding affinity to FcγRIIIa and FcγRIIIb, but not to FcγRIIa, compared with antibodies with a high amount of Fc fucose. Consequently, these antibodies with a low amount of Fc fucose showed enhanced phagocytosis of platelets using FcγRIIIb(+) polymorphonuclear cells or FcγRIIIa(+) monocytes as effector cells, but not with FcγRIIIa(-) monocytes. In addition, the degree of anti-HPA-1a fucosylation correlated positively with the neonatal platelet counts in FNAIT, and negatively to the clinical disease severity. In contrast to the FNAIT patients, no changes in core fucosylation were observed for anti-HLA antibodies in refractory thrombocytopenia (post platelet transfusion), indicating that the level of fucosylation may be antigen dependent and/or related to the immune milieu defined by pregnancy.

A pilot study showing differences in glycosylation patterns of IgG subclasses induced by pneumococcal, meningococcal, and two types of influenza vaccines.

The presence of a carbohydrate moiety on asparagine 297 in the Fc part of an IgG molecule is essential for its effector functions and thus influences its vaccine protective effect. Detailed structural carbohydrate analysis of vaccine induced IgGs is therefore of interest as this knowledge can prove valuable in vaccine research and design and when optimizing vaccine schedules. In order to better understand and exploit the protective potential of IgG antibodies, we carried out a pilot study; collecting serum or plasma from volunteers receiving different vaccines and determining the IgG subclass glycosylation patterns against specific vaccine antigens at different time points using LC-ESI-MS analysis. The four vaccines included a pneumococcal capsule polysaccharide vaccine, a meningococcal outer membrane vesicle vaccine, a seasonal influenza vaccine, and a pandemic influenza vaccine. The number of volunteers was limited, but the results following immunization indicated that the IgG subclass which dominated the response showed increased galactose and the level of sialic acid increased with time for most vaccinees. Fucose levels increased for some vaccinees but in general stayed relatively unaltered. The total background IgG glycosylation analyzed in parallel varied little with time and hence the changes seen were likely to be caused by vaccination. The presence of an adjuvant in the pandemic influenza vaccine seemed to produce simpler and less varied glycoforms compared to the adjuvant-free seasonal influenza vaccine. This pilot study demonstrates that detailed IgG glycosylation pattern analysis might be a necessary step in addition to biological testing for optimizing vaccine development and strategies.

Anti-ulcer polysaccharides from Cola cordifolia bark and leaves.

ETHNOPHARMACOLOGICAL RELEVANCE: Aqueous extracts of bark and leaves of C. cordifolia are traditionally used in Mali (West Africa) in the treatment of wounds and gastric ailments like abdominal pain, gastritis and gastric ulcers. AIM OF THE STUDY: To evaluate and compare the anti-ulcer and immunological activities, as well as the toxicity of polysaccharide rich water extracts from the bark and leaves of C. cordifolia. MATERIALS AND METHODS: Gastric ulcers were induced in rats and the inhibition of ulcer formation was calculated based on lesion index. Immunological activities were measured by complement fixation and macrophage activation. Toxicity was tested on brine shrimps. The two extracts were characterised by GC, Yariv-precipitation and quantification of phenolic compounds. An ethnomedical survey on C. cordifolia was carried out in Siby (Mali, West-Africa) to generate more knowledge about the traditional use. RESULTS: Bark and leaf extracts from C. cordifolia significantly inhibited the formation of gastric lesions in rodents in a dose depending manner. CCbark50 showed a high complement fixation activity in vitro. No toxicity was found. The ethnomedical survey showed that C. cordifolia was mainly used for treating pain and wounds. CONCLUSIONS: Our results shows that the bark and the leaves comprise a dose dependant anti-ulcer activity in an experimental rat model (no statistical difference between the plant parts). Clinical studies should be performed to evaluate the effect of both bark and leaves of C. cordifolia as a remedy against gastric ulcer in human.