Vaccines
by Nat Pernick, M.D.
I was happy to learn that my measles titer blood test
(technically, Measles Antibody, IgG) was positive at 4.6 Elisa units (1). This
means I have antibodies to the measles virus and do not need to get the MMR
vaccine. With a record number of measles cases in the US, including in
Southeast Michigan where I live, I wanted to ensure I was protected (2).
However, I had been told by physicians in the past to NOT get the MMR vaccine
due to my medical history, because it uses a live but weakened virus, which meant
I might be in a similar situation to newborns that were unprotected but unable
to be vaccinated (3).
In late 1983, while a first semester law student in Ann Arbor, I
felt a large, rock hard mass in my abdomen. I was diagnosed with Hodgkin
lymphoma and treated with radiotherapy.
Hodgkin lymphoma is a relatively common cancer, typically of young
adults (4), first described by Sir Thomas Hodgkin in 1832 (5). It previously
was called Hodgkin’s disease because its cause was unknown. However, we now
know that it is arises from post germinal center B lymphocytes (a type of white
blood cell) with "crippling" mutations of the IgH variable region
segment. B lymphocytes are a type of white blood cell that respond to
microorganisms by producing a large variety and number of antibodies. After
these cells are stimulated by exposure to microorganisms, they multiply and
cluster in the region of lymph nodes known as the germinal center. Then, they
multiply and mature into a plasma cell, which produces antibodies (6). Rarely,
B lymphocytes acquire crippling mutations that prevent their maturation (7).
Antibodies have a heavy chain, referred to as IgH, with constant
and variable regions, as well as a light chain. The diversity of the heavy and
light chains creates millions of antibodies that can bind to different
substances. B lymphocytes tend to be relatively unstable, which makes sense
given their physiologic function of rapidly producing millions of “daughter”
cells. To counter the inherent risk of B lymphocytes and other cells
reproducing out of control, multicellular organisms have evolved a
sophisticated process of “cell suicide,” also called apoptosis, that
intentionally destroys these cells and recycles their contents. When apoptosis
is hindered, cancer may occur.
Why Hodgkin lymphoma arises is unknown. In a paper I am finalizing
on How Cancer Arises Based on Complexity Theory (8), I propose that Hodgkin
lymphoma may be due to a “runaway” immune system, which couples the inherent
instability of activated B lymphocytes with defects in apoptosis and other
immune system control mechanisms, either congenital or acquired. The immune
system has a delicate balance between activating and dampening forces, which I
speculate occasionally undergoes major disruption by seemingly trivial events,
based on features of complex systems.
In Hodgkin lymphoma, the tumor cells, called Hodgkin
Reed-Sternberg cells after Dorothy Reed Mendenhall (9) and Carl Sternberg (10),
constitute a very small amount of the tumor mass. These cells secrete cytokines
(biologically active molecules) that recruit normal cells to the area and
change their properties to produce a mass that destroys organs and may cause
death. Remarkably, when the Hodgkin Reed-Sternberg cells are killed by
radiotherapy or chemotherapy, the normal cells revert to normal (11). Today,
Hodgkin lymphoma has a high (80-90%) cure rate, but this was not always true.
One of my high school classmates had an older sister who died of this disease.
After my diagnosis, my oncologist told me that I was immunocompromised
and should not get live vaccines. Thus, when working as a physician in a
hospital that required the MMR (for protection against rubella, or German
measles, which can cause congenital rubella syndrome (12)), I was given an
exemption. However, at age 61, after living a lifetime with better health than
almost anyone I know, I questioned if I was really immunocompromised and could
safely get the vaccine. My internist did not have an opinion. So I had the
measles test to help with the decision process (if positive, I would not need
it). As it turns out, the current MMR recommendations are to avoid the vaccine
only if “severely immunocompromised,” which clearly does not apply to me.
Last week, by coincidence, a Ukrainian pathologist sent me
microscopic images of the appendix of his 40 year old patient with measles
appendicitis (13). The measles virus induces the formation of Warthin-Finkeldey
cells, which are multinucleated cells containing the measles virus, in the
appendix and lymph nodes. They indicate the presence of measles virus, but have no other known significance.
This past week I also decided to get the Shingrix vaccine against
shingles, which is recommended for healthy adults age 60 or older (14).
Although in short supply, the vaccine was available at Maple Pharmacy in West
Bloomfield. Amazingly, even with my high deductible HAP insurance, there was no
charge, but the list price is about $200 per shot. A second dose is recommended
after 2-6 months. Shingles is a very painful disease due to the chicken pox
virus which features a prominent rash and can cause encephalitis (15).
References:
1. ELISA stands for Enzyme Linked ImmunoSorbent Assay. This
laboratory method detects a “target” molecule by attaching a sample that may
contain the target to a solid substance, then adding an antibody to the target
which is linked to an enzyme. In this case, the target is the measles antibody,
so the method uses an antibody to an antibody. Then the antibody-enzyme is
washed away, but it persists if it has bound to the target, which, in this
case, means the measles antibody is present. Finally, the presence of the
enzyme (and thus the target) is detected by adding a substance which typically
changes color in the presence of the enzyme, see https://en.wikipedia.org/wiki/ELISA
3. https://www.cdc.gov/vaccines/vpd/mmr/public/index.html, https://www.nytimes.com/2019/05/02/us/measles-babies-vaccine.html
11. This is one mechanism in which dysfunctional cells influence
normal cells. They can also confer toxic properties on normal cells that are
not reversed by removal of the original cells, as described by prion proteins (https://www.cdc.gov/prions/index.html).
