Previous work on the role of immune complexes in the pathogenesis of systemic lupus erythematosus (SLE), rhematoid arthritis and related disorders will be continued. In studies on RA, mixed connective tissue disease and essential mixed cryoglobulinemia (EMC), the role of rheumatoid factors with BLA and WA cross idiotypes (XIds) will be investigated. Polyclonal RFs bearing the BLA XId appear to occur in high incidence in rheumatoid arthritis while those bearing the WA XId occur widely in EMC and primary Sjogren syndrome. The BLA group of RFs are unique in reacting with DNA nucleoprotein in addition to IgG. In RA emphasis will be placed on characterization of immune complexes containing BLA RFs. Using sensitive immunoblotting techniques non-IgG antigen cross reactive with RF and antiidiotype antibodies will be sought. Similar studies will be done on the cryoglobulin from patients with EMC and the hypothesis will be tested that antiidiotype antibody is involved in the pattern of early complement component activation seen in this disease. Newly developed mouse monoclonal anti WA XId and anti WA Id will be used on a model system in these studies. In SLE the primary emphasis will be on studying the serum low molecular weight Clq reactants to determine their relationship to the associated hypocomplementemia and antibodies to native DNA that occurs in patients with these reactants. New attempts will be made to develop an anti native DNA XId antibody that reacts only with nDNA antibodies. Such a reagent would markedly facilitate these studies.