Decoding Autoimmune Diseases Like Lupus and Sjögren's
A new world of biological regulation, hidden within our cells, is changing the fight against autoimmune diseases.
Imagine your body's immune system—designed to protect you—suddenly turning against your own tissues. This is the daily reality for millions living with systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS), two complex autoimmune diseases that often prove difficult to diagnose and treat.
For years, scientists have searched for keys to understand what causes these conditions. Today, that search has led them to a surprising discovery: microRNAs (miRNAs). These tiny RNA molecules, once considered cellular "junk," are now recognized as master regulators of our immune system. Recent breakthroughs reveal that specific miRNA patterns can distinguish SLE from pSS, offering new hope for millions affected by these conditions.
To understand the excitement in the scientific community, we first need to understand what miRNAs are and why they matter.
MicroRNAs are small, single-stranded RNA molecules, approximately 18-25 nucleotides long, that function as precise regulators of gene expression 2 . They don't code for proteins themselves but instead control whether other genes get to make their proteins.
The process works like this: a miRNA binds to messenger RNA (mRNA), the molecule that carries instructions from DNA for making proteins. This binding either leads to the degradation of the mRNA or blocks its translation into protein 2 .
DNA
mRNA
Protein
Given their influential role, it's no surprise that miRNA dysregulation has been implicated in various human diseases, including cancer, neurodegenerative conditions, and autoimmune disorders 2 . In autoimmune diseases specifically, miRNAs help direct immune cell development, differentiation, and function—processes that go awry in conditions like SLE and pSS.
In 2017, a landmark study directly compared miRNA expression patterns in SLE and pSS patients, revealing both shared and distinct miRNA signatures 3 8 . The research team used next-generation sequencing technology to analyze miRNAs isolated from peripheral blood mononuclear cells (PBMCs) obtained from 8 SLE patients, 8 pSS patients, and 7 healthy controls.
The most unique finding in pSS was the downregulation of miR-150-5p, which was not observed in SLE patients 3 8 . This particular miRNA appears linked to the different ratios of B cell populations found in pSS compared to SLE.
These distinct miRNA signatures help explain why SLE and pSS present with different symptoms despite both being autoimmune conditions.
In SLE, the widespread miRNA disruptions correlate with its systemic nature, potentially affecting multiple organ systems including skin, joints, kidneys, and the cardiovascular and nervous systems 1 .
The pronounced upregulation of miRNAs like miR-21, miR-148a, and miR-155 in SLE contributes to the breakdown of immune tolerance and promotes inflammation and tissue damage throughout the body 6 9 .
In pSS, the more focused miRNA profile aligns with its initial presentation targeting exocrine glands, leading to classic symptoms like dry eyes and dry mouth 2 7 .
However, the miRNA alterations also help explain why some pSS patients develop extraglandular manifestations affecting organs such as the lungs, liver, and peripheral nerves 2 .
| Disease | Primary Symptoms | Extraglandular/Systemic Manifestations | Key Associated miRNAs |
|---|---|---|---|
| SLE | Skin rashes, joint pain, fatigue, fever | Kidney disease, cardiovascular problems, neurological disorders 1 | miR-21, miR-148a, miR-155, miR-146a 1 6 9 |
| pSS | Dry eyes, dry mouth 2 | Arthritis, lung disease, vasculitis, neuropathy 2 | miR-150-5p (downregulated), miR-146a, miR-16, miR-21 (upregulated) 3 8 |
miR-155 represents one of the most intriguing players in autoimmunity. While early studies found it upregulated in SLE and linked to disease activity 9 , more recent research reveals a more complex picture in pSS.
A 2025 study examining plasma miRNA-155 levels in pSS patients found they were significantly decreased compared to healthy controls 5 . Treated patients had higher miRNA-155 levels than untreated patients, though both remained lower than healthy individuals 5 . These levels also correlated with specific disease features—higher miRNA-155 associated with increased erythrocyte sedimentation rate (ESR) and anti-SSB antibodies, while lower levels linked to interstitial lung disease 5 .
miR-21 has emerged as a particularly important miRNA in SLE. Research shows it's significantly upregulated in SLE patients and strongly correlates with disease activity 9 . Patients with active SLE display notably higher levels of miR-21 in their PBMCs compared to both healthy individuals and patients with inactive disease 6 .
Functionally, miR-21 promotes aberrant T cell responses in SLE by targeting PDCD4 (Programmed Cell Death 4), a protein that normally suppresses inflammatory responses 9 . This mechanism contributes to the immune dysregulation characteristic of lupus.
When SLE affects the kidneys—a serious complication called lupus nephritis—miR-203 may serve as an important warning signal. A 2025 study found significantly higher miR-203 expression in lupus nephritis patients compared to those with SLE without kidney involvement 4 . This suggests miR-203 could potentially help identify SLE patients at risk for developing kidney complications.
Dual role in autoimmunity
Disease activity correlation
Lupus nephritis biomarker
Understanding how scientists identify and analyze these miRNA signatures helps appreciate the rigor behind these discoveries. The field relies on specialized techniques and reagents:
| Tool/Category | Specific Examples | Function/Purpose |
|---|---|---|
| Sample Collection | PBMCs, plasma, serum, saliva, minor salivary gland tissue 2 5 6 | Provides biological material for miRNA analysis from different compartments |
| RNA Isolation Kits | miRNeasy Serum/Plasma Kit, Nucleospin miRNA kit 5 6 | Extracts high-quality miRNA from various sample types while maintaining stability |
| Reverse Transcription | TaqMan MicroRNA Reverse Transcription Kit, miScript RT Kit 5 6 | Converts miRNA to complementary DNA (cDNA) for amplification and detection |
| Quantification Methods | Quantitative real-time PCR (qRT-PCR), Next-generation sequencing 3 5 | Precisely measures miRNA expression levels; NGS allows discovery of novel miRNAs |
| Reference Genes | U6 snRNA, cel-miR-39-3p 4 5 6 | Provides stable reference for normalizing miRNA expression data |
Sample
Collection
RNA
Extraction
Reverse
Transcription
Quantification
& Analysis
The discovery of disease-specific miRNA signatures opens up exciting possibilities for clinical medicine:
As we better understand how specific miRNAs contribute to different disease manifestations, we can envision treatments tailored to individual patients' miRNA profiles.
The discovery that SLE and pSS each possess unique miRNA expression profiles represents more than just a scientific curiosity—it opens a new window into understanding, diagnosing, and potentially treating these complex conditions. These tiny RNA molecules, once overlooked, are proving to be powerful regulators of our immune system.
As research progresses, we move closer to a future where a simple blood test can detect your risk for autoimmune disease years before symptoms appear, and treatments can be precisely tailored to your unique genetic makeup. The road from laboratory discovery to clinical application remains long, but the remarkable progress in miRNA research offers genuine hope for millions living with autoimmune conditions.
The next time you hear about scientific discoveries at the microscopic level, remember—sometimes the smallest things make the biggest difference.