Human choriocarcinoma JAR cells constitutively express pro-interleukin-1beta that can be released with Fc(gamma) receptor engagement.

Some authors have suggested that fetally derived syncytiotrophoblasts, which form the barrier between mother and the fetus, are an integral part of a complex macrophage-cytokine network involving maternal leukocytes, decidual cells, placental tissues, and even the fetus itself. We report here that syncytiotrophoblast-like JAR cells, a human choriocarcinoma cell line, share another feature common to cells of the monocyte-macrophage lineage, the ability to secrete IL-1beta when stimulated through their Fc(gamma) receptors. We incubated JAR cells with physiologically relevant concentrations of model BSA-rabbit IgG-anti-BSA immune complexes or monomeric rabbit IgG for periods of up to 72 h. Both monomeric IgG and immune complexes induced IL-1beta from JAR cells, although levels produced by immune complexes were approximately twice those induced by monomeric IgG. IL-1beta secretion was not inhibited by cycloheximide, and Western blots of JAR cell lysates using pro-IL-1beta MAb revealed constitutive expression of a 31-kD protein, whose levels declined within 2 h of stimulation by either IgG or immune complexes, but returned to baseline within 18 h.

Composition and biological behaviour of immune complexes isolated from synovial fluid of patients with juvenile rheumatoid arthritis (JRA).

Data published from in vitro studies have shown that IgM-rheumatoid factor (RF)-bearing immune complexes possess several biological features that may contribute to their pathogenicity. However, no studies have demonstrated that such complexes exist at sites of inflammation in children with rheumatoid disease. We used two methods of sequential column chromatography to purify immune complexes from synovial fluids of children with JRA. We demonstrate that high molecular weight complexes contain IgM-RF, have not bound C4 in vivo, but activate the classical pathway in vitro. In contrast, complexes which have bound C3 in vivo do not contain IgM-RF and are weak complement activators in vitro.

Complement activation and immune complexes in early congenital HIV infection.

Previous reports from our laboratory have shown that complement activation and the presence of circulating immune complexes are features of congenital human immunodeficiency virus (HIV) infection as they are in HIV-infected adults. The studies reported here were undertaken to (a) define whether complement activation is congenitally infected infants and children involves classic, alternative, or both pathways; (b) investigate the relationship between complement activation and circulating immune complexes; and (c) determine how early in congenital HIV infection complement activation and immune complexes can be found. We report that classic complement pathway activation and C1q-binding immune complexes can be found within the first 4 months of congenital HIV infection. However, the association between classic pathway activation and immune complexes before age 10 months was weak. These data raise interesting questions about complement-mediated immune complex processing in HIV-infected infants and young children.

Complement activation and immune complexes in children with polyarticular juvenile rheumatoid arthritis: a longitudinal study.

OBJECTIVE: To determine whether levels of either circulating immune complexes (IC) or complement activation fragments change as disease activity changes in children with polyarticular juvenile rheumatoid arthritis (JRA). METHODS: Twenty-six children with polyarticular JRA were examined over a time course of 4-21 months. Plasma complement activation fragments and IC were measured by commercially available enzyme linked immunoabsorbant assays. RESULTS: Both complement activation fragments and IC levels were lower in individual children when their articular disease was inactive. Children with persistently active disease had no change in any of these measures. CONCLUSION: Elevated levels of plasma IC and complement activation fragments are features of active polyarticular JRA. We believe our data support a role for the complement system in the pathophysiology of polyarticular JRA.

A comparison of immunoglobulin G-containing high-molecular-weight complexes isolated from children with juvenile rheumatoid arthritis and congenital human immunodeficiency virus infection.

Circulating immune complexes have been described in both juvenile rheumatoid arthritis and in AIDS. We isolated high-molecular-weight complexes from plasma of children with juvenile rheumatoid arthritis and congenital human immunodeficiency virus infection by sequential gel filtration followed by affinity chromatography on protein A-Sepharose. We demonstrate that 1) mixed IgG-, IgM-, and IgA-bearing immune complexes can be found in both juvenile rheumatoid arthritis and congenital human immunodeficiency virus infection and 2) complexes isolated via affinity chromatography on protein A-Sepharose do not have detectable C4 but activate the classic complement pathway in vitro.

Rheumatoid factor expression and complement activation in children congenitally infected with human immunodeficiency virus.

Rheumatic disease manifestations and autoimmune phenomena are common in adults infected with human immunodeficiency virus (HIV). On the other hand, rheumatic disease manifestations are rare in children congenitally infected with HIV. We studied the relationship between autoimmune phenomena and rheumatic diseases by examining HIV-infected children for the presence of rheumatoid factors (RFs), immune complexes, and complement activation fragments. RFs (principally IgA) were detected in 12 of the 24 HIV-infected patients (50%) and in none of the uninfected (HIV-exposed, seroreverted) controls (n = 22). Mean levels of complement activation fragments C3a and Bb were elevated in the HIV-infected children compared with the controls. A correlation was seen between the presence of IgA RF and alternative complement pathway activation as measured by plasma levels of Bb. None of the children had clinical or laboratory evidence of rheumatic disease.

Complement activation and immune complexes in juvenile rheumatoid arthritis.

We investigated the potential role of the complement system in juvenile rheumatoid arthritis (JRA) by examining plasma for levels of complement activation fragments C4d and Bb. We correlated findings with both disease activity and laboratory abnormalities, including immune complex (IC) levels. While there was a strong correlation between active disease and both C4d and Bb plasma levels in JRA, no strong correlations could be made between IC levels and complement activation products; weak associations were seen between complement activation fragments and erythrocyte sedimentation rate. Our data suggest that plasma complement activation is a concomitant of active disease in JRA; however, its role in the pathophysiology of JRA remains uncertain.