The Localization of in Vivo Bound Complement in Tissue Sections

Abstract

A technique has been described for the demonstration of a human complement component by an immunofluorescent method. The component detected is ß1C-globulin, a moiety of the third complement component, which has previously been obtained in pure form and to which a specific antiserum has been prepared. It has been shown in a model system that the binding of ß1C-globulin as shown by immunofluorescence is strictly equivalent to complement fixation as assessed by standard serological methods. This technique has been applied to the detection of in vivo bound complement in pathological human tissues. It was found that in vivo complement binding occurs in the lesions of several human diseases, but not elsewhere in the same tissues. In a rather limited survey of diseases that has been carried out, in vivo complement binding was found particularly in systemic L.E., various nephritides, and amyloidosis, as well as in single cases of some other diseases. The spectrum of in vivo complement binding has been compared with that of γ-globulin binding (7S and 19S types) and with the demonstration of in vitro complement fixation and rheumatoid factor fixation. It was distinct from each of these. Rheumatoid factor fixation, detected by anti-19S antiserum showed promise as a method for the detection of antigen-antibody complexes and aggregated γ-globulin in tissue sections. The interpretation of these findings in regard to the nature of the binding sites, and their possible significance in regard to pathogenic mechanisms have been discussed.

Experimental Induction of Athero-Arteriosclerosis by the Synergy of Allergic Injury to Arteries and Lipid-Rich Diet

“…Since childhood he had experienced repeated attacks of asthma and many episodes of urticaria. Allergy is probably an important causative factor in rheumatic cardiovascular disease (16,(23)(24)(25)(26)(27) and in the cardiovascular disease of disseminated lupus erythematosus (30,(57)(58)(59)(60)(61)(62)(63)(64)(65). Furthermore, it has long been known that rheumatic injury to coronary arteries occurs and in some cases leads to sclerosis of these vessels (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19); and clinico-pathologic observations indicate that injury to coronary arteries caused by disseminated lupus erythematosus also occurs and can lead to sclerosis of these arteries (66,67).…”

Autoantibodies against Complement C1q Specifically Target C1q Bound on Early Apoptotic Cells

“…This view is based on the following observations: First, almost all patients with C1q deficiency develop a lupus-like syndrome, with homozygous C1q deficiency being the strongest disease susceptibility gene for the development of SLE (3,4). Second, a substantial number of patients with SLE develop hypocomplementemia with depletion of C1q and other components of the classical pathway of complement (5) and C1q is deposited in affected tissues (6,7). Last, in about one-third of unselected SLE patients, autoantibodies to C1q can be detected, and they are strongly associated with the occurrence of severe lupus nephritis as well as the consumption of C1q (8 -10).…”

“…Nevertheless, there are indirect links from C1q to SLE: in particular, during flares a substantial number of SLE patients develops hypocomplementemia of the components of the classical pathway of complement, including C1q. Second, C1q is well known to be deposited in affected tissues (6,7). Last, autoantibodies against complement C1q are frequently found in patients with SLE with a strongly increasing prevalence in case of renal flares (28).…”

Immunoconglutinin in various rheumatic diseases and certain diseases suspected of an autoimmune pathogenesis

“…In 73 per cent of the determinations, titers in excess of 1/16 were obtained. 10 with acute primary gout, and 9 with osteo-and traumatic arthritis. Six patients with SLE in complete remission were also tested (Fig.…”