The immune factor interferon-lambda may be a key driver of lupus nephritis, according to a recent study that showed persistently high levels of the factor were linked to a poor response to treatment.
The study, “Interferon (IFN)-λ is a potential mediator in lupus nephritis,” was published in the journal Lupus Science & Medicine. It indicates that it may be worth exploring interferon-lambda as a treatment target for severe lupus nephritis.
Researchers at Karolinska University Hospital and Karolinska Institutet in Sweden detected that the levels of interferon-lambda in the blood serum of lupus nephritis patients were higher than in control subjects.
Another immune cytokine, interferon-alpha, also was increased among the patients, compared to the 163 controls. To allow researchers to study the impact of treatment on the kidney disease, all 56 patients provided kidney biopsies before and after treatment for their condition.
All patients received corticosteroids, but the type of additional treatment varied. The majority, 40 patients, received Cytoxan (cyclophosphamide), while nine were treated with CellCept (mycophenolate mofetil) and six with Rituxan (rituximab). One patient was treated with Azasan (azathioprine).
The team assessed the response to treatment, after a median of seven months, by analyzing kidney tissue samples. The microscopic analysis showed 38% of patients responded to treatment, while kidney disease had not improved in 62%.
Looking at the entire patient group, the team noted that interferon-alpha levels had decreased during the treatment period, while interferon-lambda remained unchanged. It turned out that patients who did not respond to treatment were driving this lack of change.
Taking a separate look at those who did respond to treatment, the interferon-lambda levels had decreased. In contrast, there was no association between interferon-alpha and liver disease response, although interferon-alpha levels were linked to the presence of certain autoantibodies and other immune factors.
To obtain further evidence of the involvement of interferon-lambda specifically in kidney disease, the team analyzed the presence of the cytokine in the kidney tissue samples. Before treatment, they found interferon-lambda in kidney glomeruli and in infiltrating immune cells.
In patients who responded to treatment, the factor was present at lower levels, without any presence in glomeruli. The different profiles of the two immune cytokines show that specific symptoms in lupus may be guarded by separate immune mechanisms.