What Is Autoimmune Lymphoproliferative Syndrome? Symptoms, Causes, and Treatment
Updated: 2 days ago
Medically reviewed by Dr. Baraa Alnahhal, MD · Last reviewed: October 2026
Quick Answer: What is ALPS?
Autoimmune lymphoproliferative syndrome (ALPS) is a condition in which the body overproduces lymphocytes that do not die off when they should, usually because of a FAS gene variation. [1] [2] Symptoms often begin in childhood with swollen lymph nodes and an enlarged spleen, and it raises lymphoma risk. [1] Medicines manage flare-ups, and a stem cell transplant is the only cure. [1]
Key Takeaways
ALPS makes the body produce far more lymphocytes than it needs, and the extra cells do not break down as they should. [1]
Without targets to attack, the leftover lymphocytes damage healthy tissue in the lymph nodes, spleen, liver, kidneys, nerves, blood vessels, and eyes. [1]
In most cases a genetic variation in the FAS gene causes ALPS, and it is inherited in an autosomal dominant pattern with a 50% chance of passing it to children. [1]
Symptoms usually start in childhood or the teenage years, most often as swollen lymph nodes and an enlarged spleen. [1]
ALPS raises lymphoma risk significantly — about 150 times higher for Hodgkin lymphoma and 14 times higher for non-Hodgkin lymphoma. [1]
No single test confirms ALPS; diagnosis relies on symptoms, blood tests, and swelling lasting more than six months. [1]
Immunosuppressants and corticosteroids manage symptoms during flare-ups, but a stem cell transplant is the only cure. [1]
What the research says
Most ALPS traces back to the FAS gene, including less obvious variants. In a large cohort of ALPS patients, about 30% had mutations in the extracellular region of FAS, and 70% of those were nonsense, splice-site, or frameshift changes that cause low FAS levels (haploinsufficiency) rather than a dominant-negative effect. (Kuehn et al., J Immunol, 2011) [2]
Genetic testing confirms ALPS in only a minority of suspected cases. Among 802 patients tested with an ALPS gene panel, 62 (7.7%) received a definite diagnosis, 52 (6.5%) of them with a pathogenic FAS variant; the yield rose to 30% when abnormal ALPS immunology findings were also present. (Xu et al., J Clin Immunol, 2024) [3]
Targeted drugs are changing treatment, and adult-onset cases are recognized. A review of nearly 500 patients from more than 300 families reported that mycophenolate mofetil, sirolimus, and pentostatin have been used successfully in ALPS, and that adult presentations are increasingly diagnosed. (Li et al., Clin Rev Allergy Immunol, 2016) [4]
What Is Autoimmune Lymphoproliferative Syndrome?
Autoimmune lymphoproliferative syndrome (ALPS) is a condition that makes the body produce too many immune cells. People with ALPS carry far more lymphocytes, a type of white blood cell, than they need — and those extra cells do not break down when they should. [1]
Normally, the body creates lymphocytes and sends them to attack dangerous cells when the immune system detects a threat. But in ALPS, the body cannot keep track of making the right amount. It keeps making too many. [1]
Without targets to attack, the extra lymphocytes damage the body instead of protecting it. [1] ALPS can lead to damage in organs and cells throughout the body, including the:
Body Area Affected | What Happens |
Lymph nodes | Swelling from immune cell buildup |
Spleen | Enlargement from excess immune activity |
Liver | Enlargement from immune cell damage |
Blood cells | Immune system attacks its own cells |
Kidneys | Tissue damage from overactive immunity |
Nerves | Nerve pain and irritation |
Blood vessels | Inflammation and damage |
Eyes | Inflammation such as uveitis |
What Are the Symptoms of Autoimmune Lymphoproliferative Syndrome?
ALPS symptoms vary from person to person. Which symptoms appear depends on where the extra white blood cells cause damage in the body. The most common symptoms include:
Symptom | What It May Look Like |
Swollen lymph nodes | Visible or felt lumps, often the first sign |
Enlarged spleen | Fullness or swelling in the upper left abdomen |
Enlarged liver | Fullness or swelling in the upper right abdomen |
Skin rashes or hives | Red, raised, itchy patches on the skin |
Nerve pain | Burning, tingling, or shooting pain |
Uveitis | Inflammation inside the eye |
Unusual bleeding | Bleeding that occurs without a clear cause |
Easy bruising | Bruises appearing from minor contact |
Unexpected weight loss | Losing weight without trying |
Symptoms usually start in childhood or the teenage years. [1] Swollen lymph nodes and spleen enlargement are often the first signs. [1] But new or different symptoms can develop throughout life as the condition progresses.
What Causes Autoimmune Lymphoproliferative Syndrome?
The FAS gene helps the body make a special protein that tells cells to break down at the right time. [1] Usually, lymphocytes automatically die off after they finish fighting harmful cells. [1] With a changed FAS gene, the cells lack that protein — meaning there is no built-in self-destruct code.
This creates a two-part problem. Lymphocytes last longer than they should, and the body does not know when to stop making new ones. [1] That combination leads to the buildup. The lymphocytes keep trying to attack but have nothing helpful to attack, so they turn on the body and start damaging it.
The genetic change follows an autosomal dominant pattern. If one biological parent carries the altered FAS gene, each child has a 50/50 chance of inheriting it. [1]
Aspect of the Cause | How It Works |
Root cause | Genetic variation, usually in the FAS gene |
Missing protein | The FAS gene normally produces a protein that tells cells to break down on time |
Result of the change | Lymphocytes do not die off and are overproduced, causing buildup |
Inheritance pattern | Autosomal dominant |
Chance of passing it on | 50% if one biological parent has the altered gene |
What Are the Complications of Autoimmune Lymphoproliferative Syndrome?
Having ALPS severely increases the risk of lymphoma, a cancer of the lymph system. People with ALPS are about 150 times more likely than average to develop Hodgkin lymphoma, and about 14 times more likely to develop non-Hodgkin lymphoma. [1]
An overactive immune system running for too long can also trigger other autoimmune diseases. [1] People with ALPS might develop:
Possible Complication | Description |
Hodgkin lymphoma | Risk is roughly 150 times higher than average |
Non-Hodgkin lymphoma | Risk is roughly 14 times higher than average |
Autoimmune hemolytic anemia | The immune system destroys red blood cells |
Autoimmune neutropenia | The immune system attacks neutrophils |
Immune thrombocytopenia | The immune system destroys platelets |
Vasculitis | Inflammation of the blood vessels |
Autoimmune hypersplenism | The spleen becomes overactive and destroys blood cells |
To learn more about one of these complications, see our guide to autoimmune hemolytic anemia.
How Is Autoimmune Lymphoproliferative Syndrome Diagnosed?
There is no test that confirms ALPS for sure. [1] Instead, providers build the diagnosis from symptoms, examination findings, and blood work over time.
A healthcare provider starts by discussing symptoms — which ones occurred, when they started, and how quickly they changed — and performs a physical exam that checks for swelling, especially in the lymph nodes and spleen. [1]
Blood tests are a key part of the workup. Providers check for unusually high amounts of lymphocytes in the blood. They may also check for high levels of double-negative T cells, a specific type of lymphocyte that is normally present only in very small numbers but is noticeably higher in people with ALPS. [1]
Having extra lymphocytes in the blood together with an enlarged spleen and/or swollen lymph nodes that last longer than six months is usually a strong clue. [1] If both signs are present, there is a good chance the condition is autoimmune lymphoproliferative syndrome.
Diagnostic Step | What It Involves |
Symptom discussion | Which symptoms, when they started, how quickly they changed |
Physical exam | Checking for swelling in lymph nodes and spleen |
Blood tests | Looking for unusually high lymphocyte counts |
Double-negative T cell check | Measuring a lymphocyte type that is elevated in ALPS |
Duration of signs | Swelling and extra lymphocytes persisting beyond six months |
Family history | Whether parents or relatives have ALPS |
Telling the provider about any biological parents or family members with ALPS can also help guide the diagnosis. [1]
How Is Autoimmune Lymphoproliferative Syndrome Treated?
The goals of treating ALPS are preventing organ damage and managing symptoms. [1] A healthcare provider will monitor the white blood cell count and watch for swelling in the spleen and lymph nodes. [1]
Providers may suggest treatments that slow the immune system down:
Treatment Option | How It Helps |
Immunosuppressants | Medications that reduce the immune system’s activity |
Corticosteroids | Prescription anti-inflammatories that also act like immunosuppressants |
Targeted symptom treatments | Other therapies matched to specific symptoms or autoimmune diseases that develop |
Stem cell transplant | The only cure; replaces the natural immune system with donor cells |
It is important to understand what these medications can and cannot do. Immunosuppressants and corticosteroids do not stop the body from making too many lymphocytes — they only manage symptoms. Because of this, they usually are not taken all the time. A provider will typically suggest them during symptom flare-ups. [1]
Is There a Cure for Autoimmune Lymphoproliferative Syndrome?
A stem cell transplant is the only cure for ALPS. [1] The procedure replaces the natural immune system with cells from a donor. [1]
Because a stem cell transplant carries significant risks and side effects, providers usually reserve it for severe ALPS that is causing dangerous complications. [1] Most people start with medications that calm the immune system and manage symptoms as they flare.
What Can I Expect If I Have Autoimmune Lymphoproliferative Syndrome?
There is no single outlook that applies to everyone with ALPS — it affects everyone differently. [1] Some people experience only minor symptoms that need occasional management. Others develop severe symptoms and dangerous complications. [1] A healthcare provider helps each person understand what to expect in their unique situation.
Because ALPS is genetic, a person with the condition has a 50% chance of passing it to their biological children. [1] Genetic counseling can help address concerns about inheritance and family planning. [1]
Ongoing care includes regular check-ups and blood tests to monitor changes in the condition. There is no test to screen for lymphoma, so knowing the warning signs matters. [1] Tell a provider right away if any of the following appear:
Lymphoma Warning Sign | Why It Matters |
New swelling in the lymph nodes | Lymphoma most often begins in the lymph system |
Fatigue | Can signal the cancer or blood cell problems |
Severe night sweats | A classic lymphoma symptom |
Shortness of breath | May indicate lung or chest involvement |
Unintentional weight loss | Rapid weight loss without trying is a red flag |
What Questions Should I Ask My Doctor?
Talking through the right questions helps people with ALPS stay on top of their condition. Here are useful questions to bring to appointments:
Question | Why It Helps |
Which of my symptoms are signs of a flare-up? | Makes it easier to catch changes early |
How often should I have blood tests? | Keeps monitoring on a predictable schedule |
What symptoms could signal lymphoma? | ALPS raises lymphoma risk significantly |
Should I see a genetic counselor? | ALPS can be passed to children with a 50% chance |
When would a stem cell transplant be right for me? | It is the only cure but carries serious risks |
What new symptoms should prompt a call? | Small changes can be early clues to complications |
Conclusion
Autoimmune lymphoproliferative syndrome (ALPS) is a rare genetic condition in which the body overproduces immune cells that fail to shut down, damaging healthy tissue instead of protecting it. [1] [5] Symptoms typically begin in childhood or the teenage years, most often as swollen lymph nodes and an enlarged spleen, and can grow to affect the liver, kidneys, nerves, blood vessels, and eyes. [1] The condition also raises the risk of lymphoma and other autoimmune diseases, which is why regular monitoring matters. [1] While medications calm flare-ups, a stem cell transplant remains the only cure. [1]
If you notice persistent swelling in your lymph nodes, unexplained bruising or bleeding, rashes, or unexplained weight loss — especially in a child or teenager — it is worth a conversation with a healthcare provider.
Frequently Asked Questions
What is autoimmune lymphoproliferative syndrome in simple terms?
Autoimmune lymphoproliferative syndrome (ALPS) is a condition in which the body makes too many white blood cells called lymphocytes, and those extra cells do not die off when they should. [1] With nothing to attack, they stay active and damage healthy tissue throughout the body. [1]
Is autoimmune lymphoproliferative syndrome genetic?
Yes. In most cases, a genetic variation in the FAS gene causes ALPS. [1] [2] The condition follows an autosomal dominant pattern, so if one biological parent has the altered gene, each child has a 50% chance of inheriting it. [1]
At what age does ALPS usually start?
Symptoms usually begin in childhood or the teenage years. [1] Swollen lymph nodes and an enlarged spleen are often the first signs [1], though new or different symptoms can develop throughout life.
Does ALPS cause cancer?
ALPS does not directly cause cancer, but it severely raises the risk of lymphoma. [1] People with ALPS are about 150 times more likely to develop Hodgkin lymphoma and about 14 times more likely to develop non-Hodgkin lymphoma compared with the general population. [1]
How is autoimmune lymphoproliferative syndrome diagnosed?
There is no single definitive test. Providers diagnose ALPS using symptom history, a physical exam, and blood tests showing unusually high lymphocytes and elevated double-negative T cells, combined with enlarged spleen or lymph nodes lasting more than six months. [1]
What are double-negative T cells?
Double-negative T cells are a type of lymphocyte that normally exists in the blood only in very small numbers. People with ALPS usually have noticeably higher amounts, making this measurement a useful diagnostic clue. [1]
Can ALPS be cured?
Yes — a stem cell transplant is the only cure. It replaces the natural immune system with donor cells, but it carries significant risks, so providers typically reserve it for severe cases with dangerous complications. [1]
What medications treat ALPS?
Immunosuppressants reduce the immune system’s activity, and corticosteroids act as prescription anti-inflammatories with immunosuppressive effects. Neither stops the overproduction of lymphocytes; both manage symptoms, usually during flare-ups rather than continuously. [1]
Can autoimmune lymphoproliferative syndrome be passed to children?
Yes. A person with ALPS has a 50% chance of passing the condition to each biological child. [1] Genetic counseling can help families understand the inheritance pattern and plan ahead. [1]
What symptoms should prompt a call to a doctor with ALPS?
Tell a provider right away about new swelling in the lymph nodes, fatigue, severe night sweats, shortness of breath, or quickly losing weight without trying. Because there is no screening test for lymphoma, these signs deserve immediate attention. [1]
Does ALPS always cause severe symptoms?
No. The outlook varies widely. Some people have only minor symptoms needing occasional management, while others develop severe symptoms and dangerous complications. [1] A healthcare provider helps each person understand their individual prognosis.
How often should someone with ALPS be monitored?
People with ALPS need regular check-ups and blood tests to monitor white blood cell counts and swelling in the spleen and lymph nodes. [1] The monitoring schedule depends on how active the condition is.
Related Reading
References
Cleveland Clinic. Autoimmune Lymphoproliferative Syndrome (ALPS). Cleveland Clinic Health Library. Last updated September 24, 2025. https://my.clevelandclinic.org/health/diseases/autoimmune-lymphoproliferative-syndrome
Kuehn HS, Caminha I, Niemela JE, et al. FAS haploinsufficiency is a common disease mechanism in the human autoimmune lymphoproliferative syndrome. J Immunol. 2011;186(10):6035-6043. PMID 21490157. https://doi.org/10.4049/jimmunol.1100021
Xu X, Denton J, Wu Y, et al. Genetic testing in patients with autoimmune lymphoproliferative syndrome: experience of 802 patients at Cincinnati Children’s Hospital Medical Center. J Clin Immunol. 2024;44(7):166. PMID 39060684. https://doi.org/10.1007/s10875-024-01772-z
Li P, Huang P, Yang Y, et al. Updated understanding of autoimmune lymphoproliferative syndrome (ALPS). Clin Rev Allergy Immunol. 2016;50(1):55-63. PMID 25663566. https://doi.org/10.1007/s12016-015-8466-y
MedlinePlus. Autoimmune lymphoproliferative syndrome. MedlinePlus Genetics, U.S. National Library of Medicine. Last updated December 1, 2018. https://medlineplus.gov/genetics/condition/autoimmune-lymphoproliferative-syndrome/
Medical disclaimer
This article is for informational purposes only and is not a substitute for professional medical advice. Always consult a qualified healthcare provider for diagnosis and treatment.
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