Search

We investigated the presence of IgG and IgA antibodies to C1q in serum samples from 80 patients with rheumatoid arthritis (RA), 31 patients with rheumatoid vasculitis, and 80 healthy controls. IgG and IgA antibodies to C1q, as measured by enzyme-linked immunosorbent assay, were found in less than 5% of the sera from RA patients and from healthy controls. In contrast, IgG and IgA antibodies to C1q were found in 29% and 61%, respectively, of the sera from patients with rheumatoid vasculitis. The occurrence of IgA antibodies to C1q has not been previously demonstrated. These results also demonstrate that IgG antibodies to C1q do not occur exclusively in systemic lupus erythematosus patients: Sera of patients with rheumatoid vasculitis frequently contain IgG or IgA antibodies to C1q, which contribute to immune complex formation.

An experimental immune synovitis was induced in the knee joints of rabbits by repeated intraarticular injections of autologous and homologous lgG or lgG derivatives. Only in those animals which demonstrated cellular immunity by skin hypersensitivity and macrophage migration inhibition did we produce a significant synovitis. Synovial lysosomal enzyme actvity was significantly elevated in these rabbits. Cyclophosphamide had no effect on inhibiting the synovial response while ALS either markedly reduced or eliminated the synovitis.

We describe a patient with a solitary plasmacytoma of the skull, in whom mononeuritis multiplex was the presenting manifestation. Some features of the POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal [M] protein, skin changes), including thrombocytosis, were found. Muscle and nerve biopsies disclosed a small vessel hypersensitivity-type vasculitis and complement-fixing immune complex deposits in vessel walls. Removal of the plasmacytoma resulted in clinical improvement and clearance of the vasculitis and immune complex deposits.

NZB/NZW F1 female mice were treated with the immunosuppressive enzyme L-asparaginase (Asnase) for up to 32 weeks. Asnase diminished circulating anti-DNA and antinuclear antibodies, diminished deposition of γ-globulins in kidneys, significantly delayed the onset of proteinuria, and reduced deaths from nephritis. These effects were associated with reduction of cellular IgM antibody synthesis to both T-dependent and T-independent antigens, but the graft-versus-host reaction was not affected. After several weeks of therapy, antibodies against Asnase appeared in the circulation, the effect on antibody synthesis was lost, ANA and anti-DNA appeared, followed by proteinuria and deaths from nephritis. Therefore Asnase proved to be an effective therapy in NZB/NZW mice, but its usefulness was limited by the appearance of inactivating antibodies.

In serum samples from 37 patients with ankylosing spondylitis (AS), immune complexes were quantitated by the 125I-Clq binding test; in paired plasma samples the C3 breakdown product C3d was measured by an immunochemical method. Compared to results in 30 blood donors, the Clq binding activity was significantly (greater than 2 SD), although discretely, increased in 5 of 8 patients with seropositive AS, but not in other AS patients. All C3d levels were within the normal range. In a parallel investigation, increased Clq binding activity and C3d levels were found in 87% and 90%, respectively, of patients with seropositive rheumatoid arthritis.

Oral administration of a stable analog of prostaglandin E1 (PGE1) 15-(S)-15-methyl-prostaglandin E1, can suppress both chronic adjuvant-induced polyarthritis and acute immune complex-induced vasculitis in a dose dependent manner. Histopathologic studies of tibiotarsal joints from rats with adjuvant disease showed suppression of arthritis in animals treated with the PGE1 analog from time of adjuvant challenge. This study represents the first demonstration of suppressed experimental polyarthritis by an orally administered prostaglandin. Suppression of the acute immune complex-induced vasculitis was demonstrated using 15- methyl-PGE1 administered orally 12 hours prior to antigen-antibody challenge. Diminution of tissue injury resulting from immune complex-induced vasculitis is reflected by a decrease in vaso-permeability, indicating suppressed vascular damage in animals treated with prostaglandin. These studies demonstrate the potential use of orally active prostaglandins as an antiinflammatory agent.

Renal biopsies from patients with a variety of immune type renal diseases were examined by immunofluorescence for the presence of C3 and its control protein, beta 1H globulin. Deposits of beta 1H were found in every instance (21 of 21 biopsies) in which C3 deposits were observed, irrespective of the underlying disease resulting in the C3 deposits, including lupus nephritis, acute poststreptococcal glomerulonephritis, idiopathic membranous glomerulonephritis, and Goodpasture's syndrome. In no instance was beta 1H found independently of C3. As previously shown in in vitro systems, beta 1H also binds to C3, presumably C3b, during activation of the complement system in immunologically induced renal disease.

An antibody-like material directed toward a thermolabile macroprotein present in all normal human sera has been identified in the sera of some patients with systemic lupus erythematosus (SLE). The antigen disappears from the serum when the antibody appears and the phenomenon is associated with hypocomplementemia and marked disease activity. The complex formed by the antigen and its antibody is intensely anticomplementary. Successful treatment of the SLE is associated with disappearance of this antibody and, over periods ranging from 1 to 9 months, reappearance of free antigen. This new antigen-antibody system appearing during the active hypocomplementemic phase of some patients with SLE may be a factor in the pathogenesis of this immune complex disease.