A visual representation of a complex immune system network.

Is Your Immune System a Double-Edged Sword? Exploring the Link Between Immunity and Arteritis

Lena Kashyap in Health & Wellness November 2025 • 4 min read.

"New research investigates whether a less active immune response increases the risk of giant cell arteritis and polymyalgia rheumatica, challenging common assumptions about immunity and autoimmune diseases."

The human immune system is a marvel of biological engineering, designed to protect us from a constant barrage of pathogens. We often think of a strong immune system as an unmitigated good, a shield against illness and disease. But what if, in some cases, a less active immune response could paradoxically increase the risk of certain health problems?

Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are two such conditions that have puzzled researchers for years. GCA is a vasculitis, an inflammation of large and medium-sized arteries, especially those in the head and neck. PMR, often occurring alongside GCA, causes muscle pain and stiffness, particularly in the shoulders and hips. Both conditions primarily affect older adults and can significantly impact their quality of life.

A recent study published in Clinical Epidemiology has dared to challenge the conventional wisdom surrounding these conditions. The researchers investigated whether individuals with a history of fewer infections, potentially indicating a less active immune system, were more likely to develop GCA or PMR. Their findings offer a fascinating glimpse into the intricate relationship between immunity and autoimmune disorders.

Hyper-Immunity: Is an Overactive Immune System to Blame?

A visual representation of a complex immune system network.

The prevailing theory behind GCA and PMR has often centered on the idea of "hyper-immunity," where an overactive immune system mistakenly attacks the body's own tissues. This concept suggests that an exaggerated immune response, rather than a deficient one, is the primary culprit.

To test this hypothesis, the researchers conducted a large population-based case-control study in Denmark. They analyzed data from over 7,000 GCA/PMR patients and compared them to a control group of over 72,000 individuals, matching for age, gender, and location. The study meticulously examined the participants' history of infections and use of anti-infective medications.

Here’s a breakdown of the study’s key methods:

Data Collection: Researchers accessed comprehensive data from Danish national health registries, including hospital records and prescription databases.
Patient Selection: The study included all patients aged 50 and over diagnosed with GCA/PMR in Northern Denmark between 1997 and 2012.
Control Group: For each GCA/PMR patient, ten control subjects were selected, matched for age, gender, residence, and time spent in the region.
Exposure Assessment: The study looked at hospital-treated infections and community-based anti-infective prescriptions to gauge infection history.
Statistical Analysis: Conditional logistic regression was used to calculate odds ratios (ORs) for GCA/PMR associated with infections, adjusting for comorbidities and immunosuppressive treatments.

The researchers initially hypothesized that a lower risk of infections, indicative of a highly effective immune system, would correlate with an increased risk of GCA/PMR. However, the results painted a different picture. After excluding infections occurring within the year before GCA/PMR diagnosis, they found no decreased risk for GCA/PMR in individuals with a history of hospital-treated infections or community anti-infective treatment. In fact, the data suggested a slightly increased risk of GCA/PMR following infections.

Rethinking the Role of Infections in GCA/PMR

These findings challenge the simple narrative of hyper-immunity leading to GCA/PMR. Instead, they suggest that incident GCA/PMR is preceded by a slightly increased risk of infection. This could mean that infections themselves might play a more direct role in the development of these conditions, or that early, undiagnosed GCA/PMR might increase susceptibility to infections.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.2147/clep.s158293, Alternate LINK

Title: Does Low Risk Of Infections As A Marker Of Effective Immunity Predict Increased Risk Of Subsequent Giant Cell Arteritis Or Polymyalgia Rheumatica? A Danish Population-Based Case&Amp;Ndash;Control Study

Subject: Epidemiology

Journal: Clinical Epidemiology

Publisher: Informa UK Limited

Authors: Clément Brault, Anders Riis, Anil Mor, Pierre Duhaut, Reimar W Thomsen

Published: 2018-10-01

Everything You Need To Know

What are giant cell arteritis (GCA) and polymyalgia rheumatica (PMR), and what connection is being explored between these conditions and the immune system?

Giant cell arteritis (GCA) is an inflammation of the large and medium-sized arteries, particularly those in the head and neck. Polymyalgia rheumatica (PMR) is a condition that often occurs alongside GCA, causing muscle pain and stiffness, especially in the shoulders and hips. Both conditions primarily affect older adults. The connection explored suggests that a less active immune system, indicated by fewer infections, might paradoxically increase the risk of developing these conditions, contrary to the common belief that these are solely caused by an overactive immune system.

How does the study challenge the prevailing theory of hyper-immunity in the context of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR)?

The study challenges the hyper-immunity theory, which posits that GCA and PMR are caused by an overactive immune system attacking the body's own tissues. The research found that a history of fewer infections did not correlate with a decreased risk of developing GCA or PMR. This suggests that factors other than, or in addition to, an overactive immune system may be at play in the development of these conditions.

What methods did the researchers use to investigate the relationship between infections and the development of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR)?

The researchers used data from Danish national health registries, including hospital records and prescription databases. They analyzed data from over 7,000 GCA/PMR patients and compared them to a control group of over 72,000 individuals, matched for age, gender, and location. They assessed infection history by looking at hospital-treated infections and community-based anti-infective prescriptions. Statistical analysis, specifically conditional logistic regression, was used to calculate odds ratios for GCA/PMR associated with infections, adjusting for comorbidities and immunosuppressive treatments.

What were the key findings of the study regarding the relationship between infections and the risk of developing giant cell arteritis (GCA) and polymyalgia rheumatica (PMR)?

The study found a slightly increased risk of GCA/PMR following infections. This suggests that infections themselves might play a more direct role in the development of GCA and PMR. It could also mean that early, undiagnosed GCA/PMR increases susceptibility to infections. This challenges the prevailing view that these conditions are solely due to an overactive immune system.

What are the limitations of this research, and what further investigations are necessary to fully understand the relationship between the immune system and the development of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR)?

While the study sheds light on the potential role of infections, it doesn't fully explain the underlying mechanisms of GCA and PMR. Further research is needed to determine how infections might trigger or exacerbate these conditions. Additionally, the study focused on a Danish population, and more diverse populations need to be studied to confirm these findings. The interplay between genetic factors, environmental triggers, and immune responses in GCA and PMR also warrants further investigation to provide a more comprehensive understanding of these conditions. It is important to consider the nuances of immune system function beyond simple "active" vs. "inactive" classifications.