Detection of an IgM Antiglobulin in the Sera of Atopic Patients Using Insolubilised IgG4, and its Capacity to Release Histamine from Leucocytes

Abstract

ELISA plates coated with highly pure IgG4 were employed to detect IgM antiglobulin in atopic sera. The use of IgG4, rather than whole IgG, on the solid-phase was to provide direct evidence for the IgG4 reactivity of the antiglobulin. Bound IgM was shown to be antiglobulin in that binding can be inhibited by pre-absorption of serum with IgG. Some 75% of asthmatic patients and 29% of eczema patients were found to have significantly raised level of IgM antiglobulin. This antiglobulin resembles rheumatoid factor in that it appears to be directed against antigenic determinants common to human and rabbit IgG. Isolated antiglobulin-enriched IgM fractions released histamine from leucocytes of 7 out of 12 atopic patients. The histamine-releasing capacity of the IgM antiglobulin was shown to be operating via basophil-bound IgG in that the process can be blocked by pre-absorption of the antiglobulin with IgG. Furthermore, heating the antiglobulin-enriched IgM fraction did not affect its histamine-releasing capacity. We conclude that the IgM antiglobulin detectable in our atopic patients may contribute to the pathological changes in them.

Role of IgG4 in ï list a mine Release from Human Basophil Leucocytes

“…Like others [6,17] we found that only donor cells who responded well to anti-lgE (i.e. showing a high 'releasability') had a reproducible but low re sponse to all the anti-IgG4 preparations tested (table II).…”

“…The fractionation was performed on two serum pools with or without high titres of mite-specific IgG4 (table I). After pooling the sera, we checked the spe cific IgG4 of the pool made from samples drawn in the late phase of an immunotherapeutical treatment (table III) in order to eliminate the possibility of pre cipitation of lgG4 by an IgM rheumatoid factor as re ported by Shakib et al [17]. We used protein-A-sepharose for the fractionation, and as aopears from table III, a small amount of IgE polluted the IgG4-rich fraction, whereas the opposite (i.e.…”

The Role of Antiglobulins in IgG4-Mediated Allergic Diseases

“…II) on plates coated with either IgG I, IgG2, IgG) or rabbit IgG. 10 Thus, this antiglobulin resembles the classical rheumatoid factor in that it appears to be directed against antigenic determinants common to human IgG subclasses and rabbit IgG, and that the activity can be absorbed out particularly efficiently with heat-aggregated IgG. However, levels in atopic sera are on the whole lower than those found in rheumatoid sera.…”

Is IgE‐mediated hypersensitivity an autoimmune disease?

“…There is a precedent for this possibility in that some individuals whose leukocytes do not release histamine when challenged with mouse monoclonal anti-IgE, will do so after subsequent addition of a goat antimouse IgG (8). That a similar situation can arise in vivo is inferred (24) from experiments (25) in which RF and RF-like (i.e. isolated from atopic patients) IgM anti-IgG preparations were shown to be capable of inducing significant (10-74.1 %) histamine release from leukocytes of atopic (asthma and eczema) patients in vitro.…”

“…4). The in vivo implications of these observations are extremely significant particularly in the pathogensis of atopic and rheumatoid disorders where both anti-IgE and anti-IgG (RF) antiglobulins are frequently present together (9,25).…”