September 19, 2025
3 min read
HUNTINGTON BEACH, Calif. — Non-nephritis lupus and lupus nephritis may actually be part of a spectrum of diseases rather than different conditions, according to a presenter at the 2025 Congress of Clinical Rheumatology West.
“We think of lupus and lupus nephritis as different diseases,” Joan T. Merrill, MD, OMRF professor of medicine at the University of Oklahoma Health Sciences Center, told Healio. “I am here to suggest to you that they are not.”
“We can be optimistic that we can do much better medicine, I can’t say in the near future, but in the future,” Joan T. Merrill, MD, told attendees. Source: Jason Laday | Healio Rheumatology
During her talk, Merrill presented a heat map of genetic expression in different patients with lupus that showed clear patterns of clusters of genes expressed in individual patients.
“Each tiny little mark on this heat map represents a module of genes that tend to be expressed higher at the same time as each other,” she said.
Lupus can essentially be divided into seven of these patterns.
“That is a finite number of patterns of things to worry about if they happen to hold up and turn out to be clinically useful,” Merrill said.
Certain patterns are marked by higher expression of type I and type II interferons, while others are marked by higher levels of inflammation, she added. Still others have high IFN expression and lower levels of inflammation, and others have more expression of T cells, B cells or plasma cells.
“These are overlapping conditions here,” Merrill said.
Regarding nephritis vs. non-nephritis, Merrill noted that every lupus patient will be assessed using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and other such measures, which also can be viewed alongside the genetic patterns described earlier.
“Renal disorder is represented in every single cluster except maybe cluster 2,” she said. “That is a very inactive cluster and we think that these people may not even have lupus. Every other cluster has a history of lupus nephritis.”
Another parameter that may provide insight on the discrepancy, or lack thereof, between non-nephritis lupus and lupus nephritis, is proteinuria.
“It is very rare to have nephritis without substantial proteinuria,” Merril said.
However, although some patients with lupus demonstrate current proteinuria, others may show signs of proteinuria in the past that resolved through medication or other methods.
“What does that imply? Maybe it implies that there are people who do not have nephritis now, but they did, and when they did, they were not in the same cluster they are in now,” Merrill said.
According to Merrill, this raises another critical consideration for rheumatologists managing patients with lupus.
“Maybe the immunologic pattern will change over time,” she said. “We wonder if lupus is seven different diseases, or whether there is an overlapping spectrum that moves from place to place.”
Merrill then brought the discussion back to IFN expression. She rearranged the initial heat map based on highest to lowest levels of IFN. That change induced different patterns of lupus disease expression.
“It is almost as if disease activity is trailing after expression of interferon,” Merrill said. “Interferon drives innate immune processes and then you get more inflammation. Do patients move with these clusters? It turns out they do.”
That said, she added that these hypotheses are “not ready for prime time.”
According to Merrill, deeper investigation into data surrounding treatments targeting proteinuria and IFN do not offer a clear picture on the differences and similarities between lupus and lupus nephritis.
However, those data do make one thing clear.
“What we have is a moving target,” she said. “How do you make a treatment last? It does not last. Perturbations drive patients into a different disarray than they were in before, and you may need a different medicine.”
Ongoing research investigating the ever-expanding therapeutic armamentarium in lupus may provide further insight into the nuances of lupus and nephritis.
However, Merrill does not expect the answer to arrive soon.
“We have the technology to begin to understand what is around us,” she said. “We have ways of structuring our data. We can be optimistic that we can do much better medicine — I can’t say in the near future, but in the future.”
For more information:
Joan T. Merrill, MD, can be reached at rheumatology@healio.com.
“We can be optimistic that we can do much better medicine, I can’t say in the near future, but in the future,” Joan T. Merrill, MD, told attendees. Source: Jason Laday | Healio Rheumatology
Sources/Disclosures
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Merrill JT. Non-Nephritis Lupus: A Different Disease? Presented at The Congress of Clinical Rheumatology West; Sept. 18-21, 2025; (hybrid meeting).
Disclosures:
Merrill reports receiving speaking fees from AbbVie, Biogen, Bristol Myers Squibb and Sanofi; research support from AstraZeneca and Bristol Myers Squibb; and consulting fees from AbbVie, Amgen, AstraZeneca, Biogen, Bristol Myers Squibb, Boehringer Ingelheim, EMD Serono, Genentech, Janssen, Eli Lilly, Merck, Novartis, Ono, RemeGen, Sanofi, Takeda, UCB and Zenas.
