C3b inactivator accelerator (A-C3bINA) was isolated from human plasma. An antiserum produced against the purified protein gave a reaction of identity with beta 1 H, a well-documented contaminant of C3 preparations. Beta 1 H appears to be composed of a single polypeptide chain containing a significant quantity of carbohydrate, and having a sedimentation coefficient of 5.6 on analytical, and 6.4 on sucrose density gradient ultracentrifugation. Its mol wt based on SDS polyacrylamide gel electrophoresis and equilibrium sedimentation is approximately 150,000, whereas it elutes from Sephadex G200 with an apparent mol wt of 300,000, suggesting that beta 1 H is an asymmetric molecule. Beta 1 H potentiates the inactivation of C3b by C3b inactivator, binds to EAC43 to limit the formation of EAC43bB and EAC43bBP, and in contrast to C3b inactivator, it increases the rate of loss of hemolytic sites from EAC43bB and EAC43bBP. For the C3b inactivator-potentiating effect, beta 1 H and C3b inactivator must necessarily be simultaneously present. The kinetics of inactivation of C3b by C3b inactivator and beta 1 H are first order, suggesting that potentiation is not a multistep process. The mechanisms of binding to C3b and inhibition of the alternative pathway convertases C3bB and C3bBP are currently unknown.

Thirty-two patients with the onset of erythema chronicum migrans, Lyme arthritis, or both in mid-1976 were studied prospectively. The skin lesion (24 patients) typically lasted about 3 weeks, beginning as a red macule or papule that expanded to form a large ring with central clearing. Associated symptoms ranged from none to malaise, fatigue, chills and fever, headache, stiff neck, backache, myalgias, nausea, vomiting, and sore throat. Three patients had been bitten by ticks at the site of the initial lesion 4 to 20 days before its onset. Nineteen patients suddenly developed a monoarticular or oligoarticular arthritis 4 days to 22 weeks (median, 4 weeks) after onset of the skin lesion; eight developed arthritis without a preceding skin lesion. Seven of these 27 experienced migratory joint pains. Arthritis attacks, most commonly in the knee, were typically short (median, 8 days) but sometimes persisted for months. Other manifestations included neurologic abnormalties, myocardial conduction abnormalities, serum cryoprecipitates, elevated serum IgM levels, and elevated erythrocyte sedimentation rates. The diagnostic marker is the skin lesion; without it, geographic clustering is the most important clue.

No abstract

The availability of hemolytically active cellular intermediates formed with components of the classical complement system has been critical to the determination of the order in which the components interact, their mechanism of interaction, and their quantitation. Although it has been possible to achieve lysis of erythrocytes by the activation of properdin factors with certain complex polysaccharides (1, 2) or cobra venom factor (CoVF) I (3), the formation of hemolytically active cellular intermediates with properdin factors has not been previously accomplished.Activation of the terminal complement sequence (C3-C9) by CoVF involves the participation of two plasma proteins: properdin factor B (4, 5), also termed C3 proactivator (C3PA) (6), and glycine-rich beta glycoprotein (GBG) (7), a 100,000 tool wt pseudoglobulin; and factor D (8), a 25,000 tool wt euglobulin, apparently identical with C3PA convertase (9) and GBGase (10). Initiation of fluid-phase reactions between factors B and D may also be accomplished by the activated form of properdin factor A (9, 11, 12), which is identical with the major cleavage product (C3b) of the third component of complement (C3).In the present study, cell-bound C3b was shown to interact with factors B and D, generating a cellular intermediate able to activate the terminal complement sequence as assessed by its lysis in the presence of C3-C9. Materials and MethodsPreparation of Plasma Proteins.--Factors B and D were prepared from pooled fresh frozen citrated human plasma as described (8). The factor B preparation yielded a single line on alkaline disk gel electrophoresis and immunoelectrophoretic analysis with goat antinormal human serum and was quantitated by radial immunodiffusion against monospecific antibody *

A human plasma protein binds to cell-bound C3b, the major cleavage product of the third component of complement. Consequent upon this binding, C3b no longer functions in either the classical or alternative pathways. This C3b inhibitory activity is a property of a protein previously designated beta 1H on the basis of its electrophoretic mobility.