A method for estimating macromolecular reflection by human synovium, using measurements of intra-articular half lives

Recent studies show that very large macromolecules in synovial fluid, such as hyaluronan and large proteoglycans, are partially reflected by the synovial lining during fluid drainage, and thus selectively retained within the cavity. Size selective molecular reflection is a fundamental property of membranes, and a method for quantifying the reflective behaviour of human synovium could be of value in several pathophysiological areas. The method proposed here is based on the intra-articular half lives of the macromolecule of interest and of a smaller, easily cleared protein such as albumin. The key relation is derived from the law of conservation of mass, using simple algebra. It is found that, when the intra-articular half lives of albumin and a macromolecular test solute are determined simultaneously, the reflected fraction of the test solute is given by the complement of the half life ratio. Examples are given. Intra-articular half lives can thus be used to consider such questions as whether immune complexes are significantly reflected by the synovial surface, how the reflective property changes in arthritides or with treatment, and how significantly reflection might influence the intra-articular concentration of large "markers" of joint disease activity.