Diagnosis and Understanding Your Lab Results
At a Glance
LRBA deficiency is usually confirmed by finding disease-causing changes in both copies of the LRBA gene. Specialized blood-cell and immune tests can support the diagnosis, but normal LRBA protein or antibody levels do not always rule it out.
The journey to a diagnosis for LRBA deficiency can be complex, often requiring a combination of advanced genetic sequencing and specialized blood tests. Because the symptoms often mimic other conditions, doctors use these labs to build a complete picture of how your immune system is functioning.
Definitive Genetic Testing
A definitive diagnosis of LRBA deficiency generally requires genetic testing that identifies biallelic mutations [1][2]. This means that both copies of your LRBA gene (one from each parent) have a pathogenic (disease-causing) change [3].
- Interpreting Variants: A genetic report may list a “variant of uncertain significance” (VUS). This means a change was found, but the lab cannot definitively say it causes disease, requiring careful specialist interpretation.
- Sequencing Methods: Most doctors start with a “Primary Immunodeficiency Panel” or Whole Exome Sequencing (WES). In some cases, if these are negative but suspicion remains high, Whole Genome Sequencing (WGS) may be needed to find rare structural changes or duplications [4][5].
- Parental Testing: It is standard practice to test both biological parents to confirm that each carries one of the mutations found in the patient, verifying autosomal recessive inheritance [3][4].
Flow Cytometry: Checking the Proteins
While genetics provides the blueprint, flow cytometry is a laboratory technique used to see how much of a specific protein is detected in your white blood cells.
Testing for LRBA Protein
Doctors may use flow cytometry to measure the abundance of LRBA protein [1].
- The Caveat: A “normal” amount of LRBA protein does not completely rule out the disease [6]. Certain types of mutations, called missense variants, may allow the body to produce a normal amount of protein, but that protein doesn’t function correctly [6][7].
Testing for CTLA-4 (The “Brake” Test)
Because LRBA’s main job is to protect the CTLA-4 protein, evaluating CTLA-4 may be part of the workup [8].
- Baseline vs. Stimulation: Specialized centers often measure CTLA-4 levels at rest (baseline) and then again after “stimulating” the cells in a lab. While this pattern can sometimes help distinguish LRBA deficiency from CTLA-4 haploinsufficiency, these assays are highly specialized, assay-dependent, and require immunology center interpretation—they are not a universal confirmation test [8][9].
Typical Immune Lab Findings
In addition to specific LRBA tests, doctors will run a broader immune workup. While every patient is unique, these findings are very common in LRBA deficiency:
- Hypogammaglobulinemia: Low levels of antibodies (IgG and IgA) are found in many patients, though some people have normal levels when they are first diagnosed [10][11].
- Low B-Cell Subsets: Most patients have low levels of “switched-memory” B cells and “plasmablasts” (mature B-cells responsible for antibody production) [10][2].
- Low Regulatory T Cells (Tregs): About 65% of patients have a reduced number of these crucial “peacekeeper” cells [10].
Specialist Evaluation Considerations
If your medical team suspects LRBA deficiency, they may consider a range of tests. Not every test is standard for every patient, and the exact panel is tailored by your specialist:
| Test Category | Tests That May Be Considered |
|---|---|
| Genetic | Biallelic LRBA mutation analysis (Panel, Exome, or Genome) and parental testing [1] |
| Protein | Intracellular LRBA flow cytometry [1] |
| Functional | CTLA-4 expression in T-cells (specialized assay) [8] |
| Antibodies | Quantitative Immunoglobulins (IgG, IgA, IgM) and vaccine titers (Note: titers can be difficult to interpret if receiving Ig replacement) [10][2] |
| Cell Counts | Lymphocyte subsets (B-cells, T-cells) and specific B-cell subsets [10] |
| Specialized | “Double-negative” T cells and Treg counts [12][10] |
Common questions in this guide
What genetic finding confirms LRBA deficiency?
What happens if an initial LRBA genetic panel is negative?
Can a normal LRBA protein test rule out LRBA deficiency?
Why might my doctor order CTLA-4 testing?
What immune lab abnormalities are common in LRBA deficiency?
How do vaccine antibody titers help evaluate LRBA deficiency?
Should parents and siblings be tested for LRBA deficiency?
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References
References (12)
- 1
Rapid Flow Cytometry-Based Test for the Diagnosis of Lipopolysaccharide Responsive Beige-Like Anchor (LRBA) Deficiency.
Gámez-Díaz L, Sigmund EC, Reiser V, et al.
Frontiers in immunology 2018; (9()):720 doi:10.3389/fimmu.2018.00720.
PMID: 29740429 - 2
The extended phenotype of LPS-responsive beige-like anchor protein (LRBA) deficiency.
Gámez-Díaz L, August D, Stepensky P, et al.
The Journal of allergy and clinical immunology 2016; (137(1)):223-230 doi:10.1016/j.jaci.2015.09.025.
PMID: 26768763 - 3
Novel compound heterozygous stop-gain mutations of LRBA in a Vietnamese patient with Common Variable Immune Deficiency.
Phan ANL, Pham TTT, Huynh N, et al.
Molecular genetics & genomic medicine 2020; (8(5)):e1216 doi:10.1002/mgg3.1216.
PMID: 32154999 - 4
Homozygous duplication identified by whole genome sequencing causes LRBA deficiency.
Merico D, Pasternak Y, Zarrei M, et al.
NPJ genomic medicine 2021; (6(1)):96 doi:10.1038/s41525-021-00263-z.
PMID: 34795304 - 5
Case Report: Exome Sequencing Reveals LRBA Deficiency in a Patient With End-Stage Renal Disease.
Taylan C, Wenzel A, Erger F, et al.
Frontiers in pediatrics 2020; (8()):42 doi:10.3389/fped.2020.00042.
PMID: 32219082 - 6
Lipopolysaccharide-responsive and beige-like anchor protein (LRBA) functional deficiency caused by biallelic LRBA missense variants characterized by Evans syndrome or colitis.
Chiang SCC, Yang L, Owsley E, et al.
The Journal of allergy and clinical immunology 2025; (156(2)):270-278 doi:10.1016/j.jaci.2025.04.003.
PMID: 40220912 - 7
Investigating concomitant RAG-2 and LRBA mutations in SCID and autoimmunity.
Spivak I, Frizinsky S, Mandola A, et al.
Clinical and experimental immunology 2026; (220(1)) doi:10.1093/cei/uxae083.
PMID: 39361308 - 8
Comparing the levels of CTLA-4-dependent biological defects in patients with LRBA deficiency and CTLA-4 insufficiency.
Catak MC, Akcam B, Bilgic Eltan S, et al.
Allergy 2022; (77(10)):3108-3123 doi:10.1111/all.15331.
PMID: 35491430 - 9
Clinical Phenotypes and Immunological Characteristics of 18 Egyptian LRBA Deficiency Patients.
Meshaal S, El Hawary R, Adel R, et al.
Journal of clinical immunology 2020; (40(6)):820-832 doi:10.1007/s10875-020-00799-2.
PMID: 32506362 - 10
Clinical, Immunologic, and Molecular Spectrum of Patients with LPS-Responsive Beige-Like Anchor Protein Deficiency: A Systematic Review.
Habibi S, Zaki-Dizaji M, Rafiemanesh H, et al.
The journal of allergy and clinical immunology. In practice 2019; (7(7)):2379-2386.e5 doi:10.1016/j.jaip.2019.04.011.
PMID: 30995531 - 11
Analysis of LRBA pathogenic variants and the association with functional protein domains and clinical presentation.
Perez-Perez D, Santos-Argumedo L, Rodriguez-Alba JC, Lopez-Herrera G
Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology 2024; (35(6)):e14179 doi:10.1111/pai.14179.
PMID: 38923448 - 12
A Spectrum of Clinical Findings from ALPS to CVID: Several Novel LRBA Defects.
Cagdas D, Halaçlı SO, Tan Ç, et al.
Journal of clinical immunology 2019; (39(7)):726-738 doi:10.1007/s10875-019-00677-6.
PMID: 31432443
This page is for informational purposes only and does not constitute medical advice. Your immunology team should interpret LRBA genetic, flow-cytometry, and immune-lab results in the context of your or your child’s care.