What is the role of a nitroblue tetrazolium (NBT) test in the workup of pediatric chronic granulomatous disease (CGD)?

Answer

The following tests are indicated in chronic granulomatous disease (CGD):

Nitroblue tetrazolium (NBT) test
- The standard assay for phagocytic oxidase activity is the NBT test. The colorless compound NBT is reduced to blue formazan by the activity of the phox enzyme system. Several versions of the test exist; each has advantages and disadvantages.
- The most efficient and informative version is the NBT slide test, in which a drop of whole blood is placed on a microscope slide coated with an activating agent, such as lipopolysaccharide or phorbol ester. Phagocytes adhering to the slide are activated and develop blue inclusions on incubation with NBT. The number of NBT-positive cells is scored under a microscope. This test is often preferred because of the small amount of blood required and the lack of a need for specialized equipment. Although the result is nonquantitative, an experienced technologist can differentiate normal phagocytes reliably from low-level phox activity observed in some cases of p47 deficiency.
- The NBT test can be useful in identifying X-linked carrier female individuals when peripheral phagocytes consist of 2 cell populations: one that reduces NBT to formazan and one that does not.
- The NBT is limited by its subjectivity, need for experienced technician, and false-negative results that cause the diagnosis of chronic granulomatous disease to be missed. False-negative findings occur when formazan accumulates in cells with low levels of active adenine dinucleotide phosphate (NADPH) oxidase. These patients clinically have the disease, but their NBT test results are negative.
- In an alternative technique, leukocytes are isolated from blood and incubated with NBT in a test tube. Formazan is solubilized by addition of an organic solvent, and the blue color intensity is read by a spectrophotometer.

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Author

Lawrence C Wolfe, MD Associate Chief for Hematology and Safety, Division of Pediatric Hematology-Oncology, Cohen Children's Medical Center

Lawrence C Wolfe, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Association of Blood Banks, American Society of Hematology, Children's Oncology Group, Eastern Society for Pediatric Research

Disclosure: Nothing to disclose.

Coauthor(s)

Elisa Keefe, MD Fellow, Department of Pediatric Hematology and Oncology, Cohen Children’s Medical Center and Feinstein Institute for Medical Research, Northshore Long Island Jewish Health System

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

James L Harper, MD Associate Professor, Department of Pediatrics, Division of Hematology/Oncology and Bone Marrow Transplantation, Associate Chairman for Education, Department of Pediatrics, University of Nebraska Medical Center; Associate Clinical Professor, Department of Pediatrics, Creighton University School of Medicine; Director, Continuing Medical Education, Children's Memorial Hospital; Pediatric Director, Nebraska Regional Hemophilia Treatment Center

James L Harper, MD is a member of the following medical societies: American Society of Pediatric Hematology/Oncology, American Federation for Clinical Research, Council on Medical Student Education in Pediatrics, Hemophilia and Thrombosis Research Society, American Academy of Pediatrics, American Association for Cancer Research, American Society of Hematology

Disclosure: Nothing to disclose.

Chief Editor

Cameron K Tebbi, MD Director, Children's Cancer Research Group Laboratories; Pediatric Hematologist/Oncologist, Tampa General Hospital and St Joseph's Children’s Hospital of Tampa

Disclosure: Nothing to disclose.

Additional Contributors

Sharada A Sarnaik, MBBS Professor of Pediatrics, Wayne State University School of Medicine; Director, Sickle Cell Center, Associate Hematologist/Oncologist, Children's Hospital of Michigan

Sharada A Sarnaik, MBBS is a member of the following medical societies: American Society of Hematology, American Society of Pediatric Hematology/Oncology, New York Academy of Sciences, Society for Pediatric Research, Children's Oncology Group, American Academy of Pediatrics, Midwest Society for Pediatric Research

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors Naynesh R Kamani, MD, and Kevin J Curran, MD, to the original writing and development of this article.

What is the role of a nitroblue tetrazolium (NBT) test in the workup of pediatric chronic granulomatous disease (CGD)?

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