Complement Activation by Alginate–Polylysine Microcapsules Used for Islet Transplantation

Abstract: A foreign body reaction is frequently observed around implanted microcapsules of alginate–polylysine. Since complement activation can play a role in this reaction, we checked in vitro the ability of empty alginate–polylysine microcapsules to activate complement. Human serum was incubated with microcapsules, and complement activation was evaluated by two methods: the complement hemolytic activity (CH₅₀) and the assay of the C3adesArg fragment. The occurrence of complement activation in the presence of microcapsules was suggested both by a CH₅₀ decrease and by high C3adesArg levels despite C3adesArg adsorption to the capsule membrane. Capsule membrane protection against the cytotoxic effects of complement was also tested. No hemolysis occurred when microencapsulated sensitized sheep erythrocytes were incubated with activated complement. In conclusion, the microcapsule membrane can protect cells against activated complement fragments. Nevertheless, alginate–polylysine microcapsules do activate complement, and this effect must be considered for its use as an implant.     

The relative importance of the X-linked FCP locus and β-globin haplotypes in determining haemoglobin F levels: a study of SS patients homozygous for βS haplotypes

Five factors have been hypothesized to influence the 20-fold variation in fetal haemoglobin (Hb F) levels in sickle cell anaemia (SS): age sex, α-globin gene number, β-globin haplotype, and the X-linked F-cell production locus (FCP) that regulates the production of Hb F containing erythrocytes (F cells). We analysed the association of these factors with Hb F levels in 112 SS patients living in France who are homozygous for the three common African β-globin haplotypes (Benin, Bantu or Central African Republic and Senegal). We found that: (1) FCP accounts for about 40% of the overall variation in Hb F levels, (2) when the FCP influence is removed, β-globin haplotype is associated with 14% of the remaining Hb F variation, and (3) the other factors have little influence. Comparison with our previous study of SS individuals in Jamaica leads to the following conclusions: (1) the X-linked FCP locus is a major determinant of Hb F levels in SS disease, (2) factors linked to the β-globin haplotype have only a small effect on the variation in Hb F levels, in either the homozygous or heterozygous state, and (3) approximately half of the variation in Hb F levels still remains to be explained.