SUMMARY The molecular weight distribution of hyaluronate (HA) in synovial fluid (SF) from 10 patients with rheumatoid arthritis (RA), from six patients with other joint disorders, and from five recently deceased persons without joint affections was investigated by a gel chromatographic procedure. A new and highly specific radioassay was used for determination of the HA concentration in the effluent from the chromatographic column, and this allowed analyses on 0-5 ml or less of untreated synovial fluid. The results confirmed the findings by others that the weight-average molecular weight (Mw) of HA in SF from patients with RA (4.8 x 106) was similar to that in other joint diseases (5.0 x 106) and moderately but significantly (p 6 x 106) is in excess in joint disease. The pathological state is therefore characterised not by lack of high molecular weight hyaluronate but by a dilution of it.

Objective. To investigate the production of type I1 collagen (CII) antibodies in the synovial fluid (SF) of rheumatoid arthritis (RA) patients, and to examine the HLA dependence of this local production.Methods. The ELISPOT method was used for enumerating anti-CII-reactive cells. Serologic tissue typing was performed.Results. Anti-CII-reactive cells were found in the SF of 16 of 31 patients, but not in any of the peripheral blood samples obtained in parallel. SF anti-CII antibody production showed no correlation with clinical parameters, but its frequency increased significantly with age. The IgG anti-CII response occurred exclusively in patients who were positive for HLA-DR4 and was significantly associated with DR4.Conclusion. Anti-CII production may be important in local immune complex formation. The indirect demonstration of a DR4-restricted T cell response to CII is an indication of a pathogenetic role of collagen autoimmunity in RA.The extent to which autoimmune reactions to type I1 collagen (CII) occur in rheumatoid arthritis (RA), and whether these reactions contribute to the

Recent animal studies show that endothelial cells in liver sinusoids are the main site for removal of sodium hyaluronate from the circulation. Few data with respect to hyaluronate metabolism are available in man. Serum hyaluronate levels were measured in 119 patients with liver disease by a sensitive assay. The hyaluronate level was significantly increased in liver cirrhosis, in comparison with healthy controls and with patients with noncirrhotic liver disease. The results suggest a role for the human liver in elimination of hyaluronate from circulation. Quantification of serum hyaluronate may be a useful test of liver endothelial cell function.

A radioassay for sodium hyaluronate using high-affinity binding protein from bovine cartilage has been modified for serum analysis. The accuracy of the method was checked by isotope dilution experiments and by recovery studies with exogenous hyaluronate. The between-assay standard deviation in the determination is 15-20%. The concentration of sodium hyaluronate in healthy adults (blood donors) is in the range of 10 to 100 micrograms/l with a mean value in the order of 30 to 40 micrograms/l. This is a lower concentration than previously reported. The same level was found in young people. Higher hyaluronate concentrations were noted in persons above 50 years of age. Analysis of plasma showed a slightly higher average hyaluronate level (5%) than in serum from the same persons. There were no notable sex differences. Analysis of serum and plasma from adult animals (rat, rabbit, dog, pig, goat, sheep, cow and horse) gave hyaluronate concentrations of the same order or higher than in human serum.

Severe corona virus disease 2019 (Covid-19) is characterized by inflammation of the lungs with increasing respiratory impairment. In fatal Covid-19, lungs at autopsy have been filled with a clear liquid jelly. However, the nature of this finding has not yet been determined.The aim of the study was to demonstrate if the lungs of fatal Covid-19 contain hyaluronan as it is associated with inflammation and acute respiratory distress syndrome (ARDS) and may have the appearance of liquid jelly.Lung tissue obtained at autopsy from three deceased Covid-19 patients was processed for hyaluronan histochemistry using a direct staining method and compared with staining in normal lung tissue.Stainings confirmed that hyaluronan is obstructing alveoli with presence in exudate and plugs, as well as in thickened perialveolar interstitium. In contrast, normal lungs only showed hyaluronan in intact alveolar walls and perivascular tissue. This is the first study to confirm prominent hyaluronan exudates in the alveolar spaces of Covid-19 lungs, supporting the notion that the macromolecule is involved in ARDS caused by SARS-CoV-2. The present finding may open up for new treatment options in severe Covid-19, aiming at reducing the presence and production of hyaluronan in the lungs.