Vincent Agnello

Reactivity of anti-histone antibodies induced by procainamide and hydralazine☆

Abstract Sera from patients with procainamide (Pr)- or hydralazine (Hy)-induced lupus were examined for anti-histone antibodies by an immunofluorescence assay using histonerecostituted mouse kidney sections and by a solid-phase radioimmunoassay using polystyrene tubes coated with purified histones. Distinct differences were observed between Pr sera and Hy sera. Pr sera were uniformly positive in the immunofluorescence assay on histone-reconstituted tissue sections, but all Hy sera were negative. In solidphase radioimmunoassay, both Pr and Hy sera showed anti-histone activity with Pr sera demonstrating strong reactions with H2A-H2B histone complex but Hy sera demonstrating weak reactions. The difference in the immunofluorescence assay could in most but not all instances be attributed to this difference in anti-H2A-H2B activity. Antibodies were not detected to DNA or to nonhistone nuclear antigens Sm, nuclear ribonucleoprotein, and SS-B La . The results indicate that both Pr and Hy induce antibodies to histones and that anti-histone antibodies induced by Pr differ both quantitatively and qualitatively from those induced by Hy.

Evidence against an immune complex pathogenesis of primary biliary cirrhosis.

In an attempt to confirm the presence of immune complexes in the sera of patients with primary biliary cirrhosis, sera of patients with primary biliary cirrhosis were studied with four sensitive radioimmunoassays. Thirty-one sera from 27 patients with well-characterized primary biliary cirrhosis, stages 1–4, were negative for immune complexes using three assays, the monoclonal rheumatoid factor inhibition assay, the C1q binding inhibition assay, and the C1q solid-phase assay. Nine of 31 sera were weakly positive with the C1q binding assay. Attempts at confirming the presence of immune complexes in sera positive in the C1q binding assay were unsuccessful because none of the sera were sufficiently positive for the reactant to be studied after fractionation. The positivity in the C1q binding assay was not due to greater sensitivity of that assay. Two assays used, the monoclonal rheumatoid factor binding inhibition assay and the C1q solid-phase assay, were 2–3 times more sensitive than the C1q binding assay. Neither could the negative results be explained by processing or storage artifacts because immediate assays of freshly drawn sera were also negative. There were no inhibitors of immune complex assays in our primary biliary cirrhosis sera. The addition of primary biliary cirrhosis sera that were negative for immune complexes to lupus serum did not inhibit the detection of immune complexes in lupus serum. To eliminate the likelihood that our negative results were due to some unrecognized methodologic problem in our own laboratory, we sent 25 primary biliary cirrhosis sera to an independent laboratory that used the Raji cell assay. Twenty-two of 25 sera were negative. In addition, at least one-third of the serum reactivity in the three positive sera was due to substances other than immune complexes. The data strongly suggest that circulating immune complexes are not involved in the pathogenesis of primary biliary cirrhosis.

Characterization of complement-fixing activity and cross-idiotypes of rheumatoid factors in idiopathic mixed cryoglobulinemia

The complement-fixing activity, specificity for IgG, and cross-idiotypes of rheumatoid factors (RF) isolated from the mixed cryoglobulins of nine patients with idiopathic mixed cryoglobulinemia were determined. All were IgM kappa and fixed complement. The RF complement-fixing activity did not correlate with hypocomplementemia or disease manifestations. The majority of RF belonged to the same cross-idiotype group. The RF from two of three patients with predominantly neurologic manifestations did not have any of the known cross-idiotypes and reacted better with rabbit IgG than with human IgG. The patients with neurologic manifestations also differed in that their serum complement was normal.

6 – COMPLEMENT DEFICIENCY AND SYSTEMIC LUPUS ERYTHEMATOSUS

The exact etiology of systemic lupus erythematosus (SLE) is not known. Hereditary complement deficiency, especially deficiency of an early complement component of the classical pathway, is a genetic factor associated with SLE and SLE-like disease in humans and most recently in mouse models with “knockout” of these components. This chapter reviews the association of hereditary and acquired complement deficiency states with SLE and SLE-like disease. The emphasis is on clinical manifestations in patients with these deficiencies, the differences in many patients from classic SLE, and the implication of these differences for current hypotheses on the specific role of the early complement components in SLE. The discussion begins with a description of the complement system. Next, the biological activities and the associations of deficiencies of the complement system with disease are described to provide the context for this review on the early components. The genetics of complement components and the clinical manifestations of genetic and acquired complement deficiencies are then reviewed with the exception of the genetics of the C4 component of complement. The chapter concludes with a speculative discussion of the role of complement deficiency in SLE, including recent studies and hypotheses on the role of early complement components in apoptosis.

Observations on Cryoglobulin Testing: II. The Association of Oligoclonal Mixed Cryoglobulinemia with Cirrhosis in Patients Infected with Hepatitis C Virus

Objective. To determine whether a mixed cryoglobulin type correlated with cirrhosis in patients infected with hepatitis C virus (HCV). Methods. We investigated the results of mixed cryoglobulin tests performed in the clinical laboratory on patients with and without HCV infection. Results. A higher prevalence of oligoclonal cryoglobulins designated Type IIa was present in HCV-infected patients with cirrhosis than in those without cirrhosis. Conclusion. An association of Type IIa cryoglobulins with cirrhosis in HCV-infected patients has not previously been reported.

Cryoglobulins Secondary to Hepatitis C Virus Infection

Publisher Summary This chapter discusses the cryoglobulins secondary to hepatitis C virus (HCV) infection. There are two types of mixed cryoglobulins: type II contains polyclonal immunoglobulin (IgG) and a monoclonal IgM rheumatoid factors (mRF), while in type III both the IgG and IgM RF are polyclonal. The manifestations of the disease range from a benign cutaneous vasculitis to life-threatening severe vasculitis of vital organs. The high frequency of hepatocellular pathology in patients with essential mixed cryoglobulinemia suggested the involvement of hepatotropic viruses in the pathogenesis of the disease.