Expression of Haemophilus influenzae type b idiotype 1 on naturally acquired antibodies

Abstract

SUMMARYThe Chinese population in Hong Kong has a low incidence of invasive Haemophilus influenzae type b (Hib) disease, as well as carriage of the microorganism. Likely stimuli for the natural antibodies to Hib, which might protect against Hib infection, are cross-reactive antigens of bacteria like Escherichia coli K100. Our aim was to determine the isotype and idiotype distribution and cross-reactivity of natural antibodies against Hib capsular polysaccharide (CP) in healthy Hong Kong Chinese. Titration of 20 sera by ELISA showed IgG antibodies reacting with Hib CP in all individuals. The antibodies were mainly IgG2, and their avidity index ranged widely. Isoelectric focusing (IEF) combined with immunoblotting showed patterns of IgG2 antibody clones against the CP of Hib and E. coli K100 which were similar in 10 cases. Absorption with Hib CP only eliminated some bands in two sera. Absorption with K100 CP did not remove any anti-Hib CP bands. In three sera additional clones of antibodies reacting to K100 CP only, disappeared after absorption with this CP. Spectrotypic analyses of IgG antibodies reacting with anti-Hib idiotype 1 (Id-1) revealed stronger IEF patterns with bands in differing locations compared with anti-Hib CP antibodies. The strong reactivity of serum IgG, IgA and IgM antibodies with monoclonal anti-Hib Id-1 was confirmed by ELISA. This reactivity was not abolished after absorption of the sera with either Hib CP, or K100 CP. The data indicate a high prevalence of Id-1 among Hong Kong Chinese. However, only one individual had Id-1 antibodies specific for Hib CP, judging from absorption experiments. Others had much lower activity of Id-1 anti-Hib CP antibodies compared with the total IgG Id-1, suggesting that Hong Kong subjects have Id-1-positive antibodies in their serum which are not specific for Hib CP. This is consistent with the nature of Id-1, which is a marker of A2V L region usage rather than a marker of a Hib CP paratope. We suggest that natural antibodies reacting with Hib CP in healthy Hong Kong Chinese are the product of exposure to some cross-reactive antigen(s), different from both Hib and E. coli K100 CP.

Risk of Invasive Haemophilus influenzae Type b (Hib) Disease in Adults with Secondary Immunodeficiency in the Post-Hib Vaccine Era

“…A specific idiotype (HibId-1, a marker of the VII-A2 chain) has been identified as the prevalent idiotype in the postvaccination adult anti-PRP antibody repertoire (22). According to our previous studies, unvaccinated adults may lack this idiotype despite high levels of natural anti-PRP, potentially induced by some cross-reactive antigens (47). In the present study, we did not see a correlation between anti-PRP IgG levels and serum bactericidal activity.…”

Signature Biochemical Properties of Broadly Cross-Reactive HIV-1 Neutralizing Antibodies in Human Plasma

“…The maximum IgG concentrations tested per fraction are shown on the right y axis. The absence of a symbol for any pseudovirus-fraction pair indicates that an IC 50 was not achieved at the highest testable IgG concentration in that fraction. and 9, neutralizing potency was greatest in basic-pI fractions (13 to 17) compared to results for the more-neutral fractions (3 to 8) for all pseudoviruses tested (P Յ 0.007; paired t test) (Fig.…”

“…4). Notably, the most potent IEF fraction (fraction 16) from subject 1 exhibited the lowest IC 50 values for all viruses tested and represented less than 2% of the entire anti-gp120 population in the Mini Rotofor fractions by ELISA. In comparison, IEF fractions from subject 2 also displayed relatively broad, albeit less potent, activity in the more-neutral fractions.…”

Expression of Idiotypic Antibodies‐1 and ‐2 and Breastfeeding in Relation to Antibody Levels Against Haemophilus Influenzae Type b in Children

“…Id‐1 is a marker of the A2VL region usage in the κ gene and of high avidity serum antibodies after Hib vaccination, but it also appears after natural exposure to Hib in both adults and children [8–10]. In adults, the IgG2 and IgA2 isotypes dominate among those with high concentrations of antibodies to Hib, whereas IgG1 and IgA1 antibodies dominate in adults with low anti‐Hib concentrations and in infants [11].…”