ALPS, or autoimmune lymphoproliferative syndrome, is a rare inherited disorder in which the body cannot properly dispose of immune cells that are no longer needed. Normally, your immune system has a built-in self-destruct mechanism that eliminates old or potentially harmful white blood cells. In people with ALPS, that mechanism is broken, so excess immune cells accumulate in the lymph nodes, spleen, and bloodstream. This leads to chronically swollen lymph nodes, an enlarged spleen, and a tendency for the immune system to attack the body’s own blood cells.
What Goes Wrong in ALPS
Your immune system relies on a process called programmed cell death to keep itself in check. When T-cells (a type of white blood cell) finish their job fighting an infection, or when they mistakenly start reacting against your own tissues, a protein called FAS on their surface triggers them to self-destruct. This cleanup process prevents the immune system from growing out of control or turning on the body.
In ALPS, mutations in the FAS gene (or, less commonly, in related genes like FASLG or CASP10) prevent this self-destruct signal from working. T-cells that should be eliminated survive and multiply instead. The result is an accumulation of a distinctive type of immune cell called “double-negative T-cells,” which lack the surface markers that normal mature T-cells carry. These rogue cells pile up in lymph tissue and contribute to autoimmune problems. Most cases are caused by FAS gene mutations, while roughly 25 percent of people with ALPS have no detectable mutation in any known gene, suggesting other genetic causes remain undiscovered.
How ALPS Is Inherited
ALPS is typically inherited in an autosomal dominant pattern, meaning a single copy of the mutated gene from one parent can cause the disease. However, not everyone who carries a FAS mutation develops symptoms. Some family members may carry the mutation and show no signs of ALPS at all, while others in the same family are severely affected. About 10 percent of people with FAS-related ALPS have a spontaneous (de novo) mutation, meaning it was not inherited from either parent.
Signs and Symptoms
ALPS usually appears in childhood, often in the first few years of life. The hallmark features are persistently swollen lymph nodes and an enlarged spleen, both of which result from the buildup of immune cells that the body cannot clear. These aren’t the temporarily swollen glands you get with a cold. In ALPS, the swelling is chronic, lasting six months or longer, and it is not caused by infection or cancer.
The other major problem is autoimmune cytopenias, conditions where the immune system destroys the body’s own blood cells. This can take several forms:
- Autoimmune hemolytic anemia: destruction of red blood cells, causing fatigue, pallor, and shortness of breath
- Immune thrombocytopenia: destruction of platelets, leading to easy bruising and bleeding
- Autoimmune neutropenia: destruction of infection-fighting white blood cells, increasing susceptibility to infections
Some people experience more than one of these at the same time. The severity varies widely. Some children have mild lymph node swelling that improves with age, while others have life-threatening drops in blood cell counts that require treatment.
How ALPS Is Diagnosed
A definitive diagnosis requires meeting two mandatory criteria plus at least one additional “primary” criterion. The two required findings are chronic (longer than six months) nonmalignant, noninfectious enlargement of lymph nodes or spleen, and an elevated percentage of double-negative T-cells, specifically at or above 1.5 percent of total lymphocytes or 2.5 percent of T-cells, with normal or elevated overall lymphocyte counts.
Once those two criteria are met, at least one of the following must also be present: a confirmed genetic mutation in FAS, FASLG, or CASP10, or a laboratory test showing that the patient’s lymphocytes fail to undergo programmed cell death normally.
Several blood biomarkers also support the diagnosis. People with ALPS caused by FAS mutations tend to have strikingly elevated vitamin B12 levels, often above 1,500 ng/L compared to a normal median around 474 ng/L. They also show high levels of certain inflammatory signaling molecules. When a combination of elevated double-negative T-cells and high B12 or elevated inflammatory markers are present together, the probability of having a FAS mutation exceeds 95 percent. These biomarkers help doctors distinguish ALPS from other conditions that can cause similar-looking lymph node enlargement, including lymphoma.
Lymphoma Risk
People with ALPS face a significantly increased lifetime risk of developing lymphoma, both Hodgkin and non-Hodgkin types. The ongoing accumulation of immune cells and chronic immune stimulation are thought to create conditions that favor cancerous transformation over time. This elevated risk means that people with ALPS need long-term monitoring, and any new or rapidly changing lymph node swelling should be evaluated promptly to rule out malignancy.
Treatment Options
Treatment for ALPS depends on which symptoms are most problematic. Mild lymph node swelling that does not cause complications may simply be monitored. When autoimmune blood cell destruction becomes significant, corticosteroids are often the first approach to suppress the immune attack.
For people whose disease does not respond well to steroids, an immunosuppressive medication called sirolimus has shown strong results. In clinical studies, three out of five patients with active lymph node and spleen enlargement had complete resolution of both problems on sirolimus, and all treated patients saw a reduction in their double-negative T-cell levels. Sirolimus works by suppressing the overgrowth of immune cells, directly targeting the core problem in ALPS. It is generally considered the go-to second-line therapy for steroid-refractory disease.
Spleen removal (splenectomy) was once more commonly performed to manage ALPS, but it carries a lifelong increased risk of serious infections, particularly in children. Because of this, and because medications like sirolimus can effectively control spleen enlargement, splenectomy is now generally avoided when possible.
Living With ALPS Long-Term
Many children with ALPS see their lymph node swelling improve as they move into adolescence and adulthood, though autoimmune cytopenias can persist or flare at any age. The condition requires ongoing blood work to monitor cell counts, vitamin B12 levels, and other biomarkers, as well as periodic imaging or physical exams to track lymph node and spleen size. Because of the elevated lymphoma risk, long-term surveillance remains important even when symptoms are well controlled. With appropriate monitoring and treatment, most people with ALPS can manage the condition effectively throughout their lives.