Tarsell v. HHS, (Fed. Cl. Spec. Mstr. Feb. 16, 2016) (Moran, SM)
The theory of the case was that the decedent developed an arrhythmia from Gardasil which caused her death. Petitioner brought an immunologist and a cardiologist to hearing. The mechanism proposed was that the HPV vaccine causes the body to produce antibodies that are misdirected against a part of the heart, known as an L1 calcium channel, and the cumulative damage to the L1 calcium channel impairs the heart’s functioning leading to arrhythmia and death.
The primary reason Petitioner lost was that the special master found she failed to establish that the onset of her arrhythmia was post-vaccinal. This was a foundational element of the claim. Moreover, the proposed theory contained too many leaps and unsupported assumptions to be persuasive. Finally, heart tissue examined by pathologists at CDC showed that the decedent did not experience damage in the way her experts’ theories predicted (a Daubert factor).
The special master reviewed the epidemiological evidence submitted noting that either the HPV vaccine has not increased the rate of deaths, or if the HPV vaccine is increasing the rate of death, then the increase happens so rarely that multiple studies have not found it.
Additionally, the special master held that there was no persuasive evidence of when the arrhythmia began. The fact that doctors had failed to detect an irregular rhythm previously was not conclusive because arrhythmias come and go. Thus, because there was no proof of onset, petitioner could not prevail.
Petitioner’s theory also failed the Althen prongs. For the first proposed mechanism, the special master found no reliable evidence that the HPV vaccine causes the body to produce antibodies to the beta-adrenergic receptors in the heart. The second proposed mechanism involved molecular mimicry as well. Notably, the special master stated: “To some [special masters], Dr. Shoenfeld’s invocation of molecular mimicry plus an identified homology would constitute a persuasive medical theory.” (Editors note: See Day, McCulloch (entitlement decisions). However, he found that the evidence persuasively showed that the LQAGL homology Kanduc discovered in 2009 is not an adequate basis for finding that a cross-reaction actually occurs, resulting in autoimmunity.
In this case, unlike most, the parties agreed that there was sequence homology, of five peptides, between the HPV vaccine and the calcium channel of the heart. The dispute was whether this was meaningful, i.e., does homology always or necessarily lead to cross-reactivity resulting in AI disease. Pentamer level homologies are common and this could be a mere coincidence. Even if cross-reactivity occurred, there was no evidence that AI damage to the calcium channel would resemble the petitioner’s clinical presentation. Thus, petitioner’s theory was not persuasive.
With regard to prong two, if there had been an autoimmune attack on some part of the heart, either the Beta-adrenergic receptors or the L1 calcium channel, one would expect to see inflammatory cell infiltrates on autopsy, but there were none. Petitioner provided no argument with respect to this discrepancy, thus could not prove that the proposed theory played out in this case.
This decision provides information to petitioners’ counsel intending to advance a molecular mimicry theory in the future. Importantly, the decision implies that a petitioner would need to put on evidence of dose-response curves, or whether sufficient antibody production occurs to cause damage if Respondent were to raise this issue in future cases.
Another potential pitfall for petitioners could arise if the proposed homologous region in the body is intracellular – is it certain that the antibodies can reach this region, perhaps through the process of endocytosis.
These are topics that have not previously played a major role in past decisions involving molecular mimicry. It used to be that establishing sequence homology was sufficient to prevail on a mimicry theory. It has become much more complicated over the past decade to prove a case based on homology alone; homologous sequences must be sufficiently lengthy and there must be an explanation why homology leads to cross-reactivity. At the same time, there are scientific arguments that have been made in several of my cases as to why no sequence homology evidence is even needed for a mimicry theory to be persuasive. These cases are scheduled for upcoming hearings. Additionally, the case reported here is on appeal. Please feel free to contact me if you have a case where the medical theory is mimicry if you’d like to discuss the evolution of the theory and the differing viewpoints of the special masters on this issue.