Immunology: What Is It Good For?

I was cleaning out an old storage closet in my parents’ house in Florida when I stumbled across some notes I took in medical school. As I leafed through pages and pages of notes filled with doodles and reminders, I found a statement that gave me pause: “Immunology—what is it good for?!”

To be honest, I don’t remember if it was something the professor had said, or whether it was a comment that came out of frustration with the dense subject matter. It was, after all, set next to a very elaborate depiction of the complement pathways. Nevertheless, I found it extremely funny that 15 years later, I would be a doctor who treats immune diseases of all varieties. Then I thought that perhaps there’s another student (or cynical lecturer) out there who has the same sentiment. As the ACR journal, Arthritis & Rheumatology, starts a series on immunology for the practicing rheumatologist, the topic is worth a second look. So, immunology—what is it good for? Let’s rheuminate.

A Deeper Understanding of Disease

The vast majority of rheumatic diseases are rooted in the immune system. In fact, I would say that almost every disease, from ankle sprains to heart attacks, has an element of immune dysfunction.¹ As we start to gain more knowledge about the pathogenesis of these diseases, we’ve started to see unmistakable evidence of cross talk between the various arms of the immune system and other organ systems. This newer, emergent body of knowledge is often dense, but it’s vital to understand because it brings us a deeper understanding of our own sense of health and illness.

A wonderful example of this is the complement cascade that my younger self seemed to bristle at. Although it doesn’t seem like I need to know every single step of the disease process to be a practicing rheumatologist, I recognize that having an appreciation for the grander scheme of these positive and negative reinforcement cycles makes me a better clinician. When I order complement levels or labs to determine complement function, such as CH50 and AH50, I use heuristics to help analyze them in a clinical context. But I wouldn’t be able to solve more complex mysteries without having that complex tripartite cascade embedded somewhere in the back of my mind.

Moreover, as I think about the expansion of biologic medications with newer mechanisms of actions, I often go back to thinking about the clinical patterns that would correlate with the immunopathogenesis. Does this seem more T cell or B cell mediated? Which helper T cell subset seems to be over- or underactive? Where along a pathway can I find an off switch? Where step therapy is very much a straitjacket that prevents us from using more appropriate medications early in disease, I can better select which immune modulator is most likely to be effective, once I fail first with insurance-mandated cheaper medications.² At the very least, it helps me craft detailed justifications for prior authorization and appeal letters.

A More Meaningful Patient-Clinician Relationship

It is not just the cerebral element of immunology that aids us as rheumatologists. Knowledge of clinical immunology is very much an important aspect of being a practicing rheumatologist. When a patient asks a question, I feel like I should have a mastery of material to allow me to confidently answer their concerns. Patients are highly discerning and they are well aware of whether their clinicians know what they are talking about, or whether they are simply following an if-then algorithm in their mind.

During the earlier days of the pandemic, this was particularly critical with respect to vaccines. Many of my patients had very legitimate concerns about mRNA vaccines, a technology that was relatively novel to them. Rather than dismissing these concerns, I felt empowered by my knowledge of immunology to have detailed conversations about how vaccines impact their immune systems, especially those with complex disorders of immune dysfunction. Providing additional, expert information they otherwise could not obtain through generic advice from the internet and social media enabled them to make a more informed choice about vaccination.

Somewhat paradoxically, greater knowledge of immunology also enables us to speak to those with less knowledge of immunology. When we are better able to express the knowledge of immunology in more accurate metaphors and stories, we are better able to connect with our patients. The hegemonic view of autoimmunity being excess immune responses is simple, but is horribly inaccurate and, at times, confusing to patients. Don’t our patients deserve to get a more accurate view of what is causing their diseases? The only way we can answer that question is to delve deeper into the world of immunology.

A Bridge to Other Rheumatologists

It’s not only the patients who benefit from a rheumatologist who is knowledgeable of the immune system. So much of the nomenclature and terminology is based in immunology, down to the connotations of the seemingly random combinations of numbers. It’s one thing to know what interleukin 8, interferon-α, TGF-β, and CXCL8 are. It’s another to know that CXCL8 and IL-8 are actually the same thing. Without this degree of knowledge, the rheumatologist is dependent on another person to control the flow of information. Even with all the information available at our fingertips within smartphones, without the familiarity with, and instant access to this knowledge, we can be led astray in even casual conversations.

Immunology so pervades the conversations of rheumatologists that even our mindsets are determined by these antibodies and white blood cells. Our inner assumptions when we hear the word spondyloarthritis are totally different than we hear the word dsDNA. But without having reinforcement of immunological concepts, these assumptions can lead to considerable miscommunication. That’s why it’s necessary for all of us to keep reinforcing our immunological knowledge; these concepts change over time.

Speaking of change, it’s vital for practicing rheumatologists to understand the basics of clinical immunology because it forms that vital connection with basic science, clinical science and translational research. Because grant writing and publication take so much time that research is now a full-time job, there is a growing chasm between clinicians and researchers. Understanding immunology can help us narrow that chasm for the interests of our patients and advancing the field.

Anti-Boredom Antibodies

Even with these elaborated reasons, there’s a deeper justification for periodically revisiting our knowledge base regarding immunology. Immunology is fun. Immunology is full of stories that we create regarding how the world works. By listening to these stories and contributing to them, we have fun and expand the magic and joy of the world around us.

So much of what drives our burnout in clinical settings is the mundane aspect of disease. As a fellowship program director, I’ve heard trainees over the years becoming more and more bored by “another case of gout.” Certainly, we can continue our career development by just dispensing allopurinol and colchicine for gout and making our income accordingly. But without a deeper exploration into why each case of gout is unique and is a mystery worth exploring, it becomes a chore to treat the condition rather than an adventure.

Immunology is also something that is intellectually stimulating. There’s an intangible joy that comes out of uncovering those connections between what appear to be disparate elements of the immune system. A patient of mine with chronic spontaneous urticaria developed ankylosing spondylitis. It seemed to be two separate conditions, but looking into the immunology, it appears there’s a role for mast cells in spondyloarthritis.³ Although that knowledge didn’t change the medication therapy plan, it provided me a lot of joy to connect these two dots and to relay it to a patient desperately looking for answers.

Diversity, Equity … & Immunology

The last reason it is vital for practicing rheumatologists to embrace immunology is because it has major ramifications on diversity, equity and inclusion. After all, even a cursory glance into the history of immunology shows a massive blind spot when examining the immune systems of patients from marginalized and minoritized communities.⁴ The clinical immunology community has been racing to identify the biases inherent within the historical dogmas of the field—and, as practicing rheumatologists, we need to be aware of these as well.

Because our patients are disproportionately from minoritized and marginalized communities, we need to better understand and reclaim the immunology that is going on within their very own bodies. Although most practicing rheumatologists don’t engage in basic science research, we contribute to conceptions, and occasionally misconceptions, of immunology as it relates to people from vulnerable communities. Ensuring that we, as practitioners, acknowledge the limitations of immunology is advisable so we can provide the best quality care for them.

Of course there are so many other reasons for my fellow rheumatologists to pick up a review article on immunology. Whatever reason you may pick, the point remains the same—without a core understanding of why we see rheumatologic diseases and how we can target them, we are not fully rheumatologists and we are not living up to our potential as healers for patients with complex immune derangements.

Even a superficial curiosity into the workings of the immune system may deepen your respect for all the different diseases and treatments that we are exposed to. And, in the process, you may discover that everyday immunology may lead to mystery and adventure that you previously thought were unimaginable.

Going back to what Student Doctor Bharat Kumar scribbled on the margins of his notebook in 2007, what exactly is immunology good for? The now-Doctor Kumar can answer that: Learning immunology is good for the soul, to keep you feeling like a student in search of truth and knowledge, no matter how distanced you are from a lecture hall or laboratory.

Bharat Kumar, MD, MME, FACP, FAAAAI, RhMSUS, is the director of the rheumatology fellowship training program at the University of Iowa, Iowa City, and the physician editor of The Rheumatologist. Follow him on X @BharatKumarMD.

References

1. Del Buono MG, Bonaventura A, Vecchié A, et al. Pathogenic pathways and therapeutic targets of inflammation in heart diseases: A focus on Interleukin-1. Eur J Clin Invest. 2023 Oct 14.
2. Boytsov N, Zhang X, Evans KA, Johnson BH. Impact of plan-level access restrictions on effectiveness of biologics among patients with rheumatoid or psoriatic arthritis. Pharmacoecon Open. 2020 Mar;4(1):105–117.
3. Polivka L, Frenzel L, Jouzeau JY, et al. Mast cells in spondyloarthritis, more than simple inflammatory bystanders? Ther Adv Musculoskelet Dis. 2020 Nov 16;12:1759720X20971907.
4. Kaufmann SHE. Immunology’s coming of age. Front Immunol. 2019 Apr 3;10:684.