Why is Alpha-1-antitrypsin High? Causes, Symptoms, and What to Do

A high alpha-1 antitrypsin (AAT) level is usually not a disease in itself. AAT is an "acute-phase" protein: the liver makes more of it whenever the body is dealing with infection or inflammation, and levels also rise in pregnancy and with oestrogen, including the contraceptive pill. A high result causes no harm and no symptoms; what matters is the reason behind it, and the fact that a raised level can hide an inherited AAT deficiency.

What alpha-1 antitrypsin is

AAT is a protein made mainly by the liver. Its main job is to protect the lungs from damage by an enzyme released by white blood cells. In inherited deficiency the liver can also be harmed, because the abnormal protein builds up in the liver instead of being released into the blood. The test is ordered mostly to look for the opposite problem: alpha-1 antitrypsin deficiency (AATD), an inherited condition in which too little AAT is made. AATD can cause early emphysema (lung damage) and liver disease, including cirrhosis.

Because of this, the test is usually done in people with COPD or emphysema, unexplained bronchiectasis or chronic liver disease, adults with late-onset asthma or airway narrowing that does not fully reverse, and close relatives of someone with AATD.

Typical values

Ranges differ between laboratories and especially between measurement methods and calibration standards, so always use the range printed on your report.

In SI units 100 mg/dL equals 1 g/L, so a range written as 1.0 to 2.0 g/L on a report is roughly the same as 100 to 200 mg/dL. A UK laboratory describes severe genetic deficiency as usually less than 0.6 g/L.

Causes of a high AAT, from most to least common

Common and usually temporary

• Infection or inflammation. As an acute-phase protein, AAT rises during infections and inflammatory diseases. Guidelines describe increases of 75% to 100% with infection or inflammation, and a UK laboratory describes a 2- to 3-fold rise. It is a slow-reacting protein, so it can stay up for a while after an illness.
• Pregnancy. AAT levels rise during pregnancy.
• Oestrogen. Oral contraceptives and other oestrogen treatment raise AAT.

Less common

• Cancer. Increased levels occur in malignancy, as part of the body's inflammatory response. A high AAT is not a test for cancer and is not used to look for it.

Why a high result can be misleading

The most important practical point is that a high or normal AAT does not rule out AAT deficiency if it was measured during an illness, in pregnancy or while taking oestrogen. Someone who carries one deficiency gene (for example PI*MZ) normally has a moderately reduced level; an infection can push it up into the normal or high range. A US hepatology reference warns that serum levels "may be falsely elevated" by this strong acute-phase response, and that the level alone is not enough to make or exclude the diagnosis.

Symptoms

A high AAT does not cause symptoms. Any symptoms come from the underlying cause: fever or cough with an infection, joint pain with an inflammatory condition, and so on. If you were tested because of breathlessness, a long-standing cough or a liver problem, those symptoms still need to be explained, and a high AAT does not explain them.

What usually happens next

• Check for inflammation. A clinician will often look at C-reactive protein (CRP). If CRP is high, suggesting an ongoing infection, guidelines advise disregarding the AAT result and repeating it.
• Repeat when well. AAT should be measured when you are in a stable phase, not during an infection or flare-up.
• Phenotype or genotype testing. If AATD is still suspected, for example in someone with COPD, emphysema or unexplained liver disease, the definitive tests are phenotyping (separating the AAT protein variants) or genotyping (looking at the SERPINA1 gene). Relatives of someone with AATD are best tested with genotyping first, because their serum level may look normal.
• Look for the cause of inflammation if it is not already obvious, guided by your symptoms and other results.

Frequently asked questions

What does it mean if alpha-1 antitrypsin is high? Most often it means your body was reacting to infection or inflammation when the blood was taken, or that you are pregnant or taking oestrogen. A high AAT itself is not harmful.

Is elevated alpha-1 antitrypsin dangerous? No. There is no disease caused by having too much AAT. The concern, if any, is about the underlying inflammation, or about a deficiency being hidden by a temporarily raised level.

Can you have alpha-1 antitrypsin deficiency with a high level? A carrier with a moderately low baseline can show a normal or high level during an infection, pregnancy or oestrogen use. If there is a strong reason to suspect AATD, phenotype or genotype testing gives the answer regardless of the level.

Does birth control raise alpha-1 antitrypsin? Yes. Oestrogen, including in oral contraceptives, increases AAT levels. Tell your doctor if you take it.

What is a normal alpha-1 antitrypsin level? In people with the usual gene pair it is about 100 to 220 mg/dL in one recent guideline, but ranges vary by method and laboratory, so use the one on your report. Severe deficiency is generally below 57 mg/dL or 11 µmol/L.

Should the test be repeated? If it was taken during an illness, or if CRP was high, repeating it when you are well gives a more reliable baseline.

When to see a doctor

A single high AAT in someone who feels well is not a cause for concern; it is worth going through with the doctor who ordered it, together with your CRP and the reason for the test. It is worth discussing with your doctor soon if you have a cough or breathlessness that has lasted weeks, yellowing of the skin or eyes, or if a close relative has AAT deficiency. Seek urgent care for severe breathing difficulty, chest pain or confusion.

Sources

1. Alpha-1 Antitrypsin Test — Testing.com
2. Alpha-1 antitrypsin blood test — MedlinePlus, U.S. National Library of Medicine
3. Recommendations for the diagnosis and treatment of alpha-1 antitrypsin deficiency (2024) — Brazilian Thoracic Society, via PMC
4. Expression of Phenotype in Alpha-1 Antitrypsin Deficiency — Merck Manual Professional Version
5. α1-Antitrypsin deficiency — South Tees Hospitals NHS Foundation Trust, Pathology
6. Alpha1-Antitrypsin Deficiency — Cleveland Clinic, Center for Continuing Education
7. Maternal serum alpha-1 antitrypsin levels in spontaneous preterm and term pregnancies (2024) — Scientific Reports, via PMC
8. Alpha-1 antitrypsin deficiency — MedlinePlus Genetics, U.S. National Library of Medicine

Decisions about your health should always be made in consultation with your healthcare provider.