PubMed · 449890
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L Krishnan, E C Krishnan, W R Jewell. 1979-06-28. Fc-receptor dysfunction in lupus.. https://pubmed.ncbi.nlm.nih.gov/449890/
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C1q-bearing immune complexes have been observed in diseases such as rheumatoid arthritis and human immunodeficiency virus infection-associated neuropathy. For the purpose of understanding better the phenomenon of C1q-bearing immune complexes, we investigated the constancy of the C1q-IgG interaction. An enzyme-linked immunosorbent assay was developed in which wells were coated with IgG to mimic antigen-complexed IgG. Serial dilutions of C1q were applied for distinct time intervals, and bound C1q was detected either directly or after exposure to one of several elution buffers. Our results show that a part of C1q attached to IgG forms a tight association that is not reversible under treatment with buffers containing usually protein-protein interaction-dissociating reagents such as 3 M NaCl, 5 M urea, sodium dodecyl sulfate, or beta-mercaptoethanol. The formation of the highly stable C1q-IgG complex was found to be time-, temperature-, and pH-dependent and to proceed with bound C1q even in the absence of free C1q in the supernatant. In ligand blotting experiments we demonstrate for the first time directly that all three chains of C1q can individually bind IgG. Altogether, our results provide a suitable explanation for the formation and persistence of C1q-bearing immune complexes.
Immune complex-dissociated (ICD) HIV-1 p24 antigen assay is a rapid technique for assessing the presence of HIV gag or core protein in plasma or serum. In this study, ICD p24 antigen detection in HIV-1 infected mothers and their infants enrolled in the Women and Infants Transmission Study (WITS) was evaluated primarily as a diagnostic assay for HIV-1 detection in young infants and for its association with perinatal transmission. Plasma from 47 infected infants and 160 uninfected infants was examined, along with plasma from 197 of their mothers who had a delivery or close-to-delivery specimen. ICD p24 antigen was detected in plasma of 27.3% of infected infants at birth and in 70% to 81% at 1 to 6 months. The diagnostic specificity at birth was 90% and 98% to 100.0% at 1 to 6 months. The ICD p24 antigen concentration correlated with concurrent quantitative HIV culture results. The risk of transmission from mother to infant was higher if the mother had detectable ICD p24 antigen at or near the time of delivery (p = 0.002), but its presence did not accurately predict transmission (positive predictive value of 36%, negative predictive values of 85%). The relative ease of performing the ICD p24 antigen assay and the low cost compared with that of HIV culture or DNA PCR makes this test a useful adjunct for the diagnosis of perinatal HIV infection and for enhancing understanding of its pathogenesis, particularly where cost and availability limit access to more sensitive assays.
To characterize the functional macromolecular complex of the high affinity receptor for IgG (Fc gamma RI), we have undertaken the identification of the molecules associated with the ligand binding unit and its associated subunit, gamma-chain, in a monocyte cell line, U937. Comparison of the pattern of tyrosine-phosphorylated proteins that coprecipitate with anti-Fc gamma RI or anti-gamma-chain Abs after Fc gamma RI clustering suggests that, like other receptor systems, the different units of the receptor associate or recruit different elements of the signaling pathway. Syk associates preferentially with the gamma-chain subunit and not with Fc gamma RI itself. This association is dependent on receptor clustering and correlates with gamma-chain phosphorylation. The Src kinase Lyn is also part of the receptor complex. Lyn associates with both units of the receptor, and this association is independent of receptor engagement; however, the level of tyrosine phosphorylation of the kinase increases after Fc gamma RI clustering. Association of a 35-kDa phosphoprotein with the binding unit was also observed after receptor clustering. We further found that after Fc gamma RI clustering, tyrosine-phosphorylated Syk associates with Lyn. These data suggest that several levels of interaction occur between these molecules or that different pools of tyrosine kinases become activated after Fc gamma RI clustering.