001422 - IgG3 antibodies specific for alpha-gal as a part of the cardiac risk profile of alpha-gal antibodies in patients living in an area with heavy tick infestation

The IgG3 isotype is generally regarded as pro-inflammatory on the basis of its ability to; activate complement, bind to activating Fc gamma receptors, and its stable hinge region.  Recently there has been increased interest in IgG3 because i) the cardiology group in Vienna reported increased specific IgG3 to alpha-ga (sIgG3) in patients with mammalian aortic valve transplants and ii) Dr. Moverare and his colleagues at Thermo-Fisher/Phadia developed the ImmunoCAP assay for sIgG3.

Specific IgE, IgG, and IgG3 Ab to alpha-gal were measured using ImmunoCAP with beef thyroglobulin.  Three cohorts were studied: 

1.  Employees in the University of Virginia who were enrolled to study COVID 19
2. Individuals with or without alpha-gal syndrome who were followed to study the response to tick bites
3. Patients (n=193) with high risk for coronary artery disease (CAD) being evaluated using intravascular ultrasound (IVUS) to estimate atheroma burden.

In keeping with previous findings, the patients being followed after tick bites had an increase in sIgG3 to alpha-gal which significantly correlated with sIgE.  Among eight subjects who had > 3-fold increase in sIgG3, three subjects had an increase to >1µg/mL: pre-tick bite, 1.2; 0.3; and 0.2 µg/mL post tick bite, 9.2, 2.8, and 1.4 µg/mL respectively. 

Among 267 subjects enrolled to study COVID, sIgE to alpha-gal was present in 41.  Compared to a random group of 41 the sIgG3 in the sensitized subjects was significantly higher p< 0.003 and correlated with both sIgG and sIgE, p<0.001 and 0.003, respectively. 

The values for sIgG3 and also sIgE and sIgG to alpha-gal among 193 patients undergoing evaluation for heart disease were compared with values for Atheroma burden derived from IVUS.  In particular Atheroma burden was compared to sIgG3 to alpha-gal using 3 groups those with >300ng/mL: 300-1000 ng/mL,

and > 1000ng/mL.  Atheroma burden was significantly associated with values over 1000ng/mL (1µg/mL)          p < 0.005 compared with those with lower levels. 

=Bites from the Lone Star Tick can induce sIgG3 as well as sIgG and sIgE antibody to alpha-gal.

= the measurements of Atheroma Burden were significantly associated with sIgG3 Ab level   >1000ng.mL

=Among subjects being followed after tick bites three subjects had an increase to > 1000ng/mL.

= The implication is that tick bites could increase the risk of CAD among individuals who eat a mammalian rich diet.