1 of 15

Interferon Gamma Receptor 1 Deficiency presenting with Mycobacterium avium intracellulare (MAC) infection

BIOL 404: Immunology

Presented by: Amy Helms, Tristana Foster, and Davice Jones

2 of 15

Summary of the Symptoms

Female child
2 ½ years old
Poor appetite
Diarrhea
Significant Weight Loss
Enlarged Lymph Nodes in the mesentery and para-aortic region
Repeated mycobacterial infections

3 of 15

Flow Cytometry Analysis

We wanted to run a Flow Cytometry to get a baseline understanding of the immune cells present in the patients system.

Flow cytometry is a common technology that uses lasers to produce light signals that are

detected and converted into electronic signals which are analyzed by a computer.

4 of 15

Flow Cytometry Results

These analyzed results for the patient showed cell populations of:

White blood cell count= 9,400 (Slightly abnormal: average range is 5,000- 9,000)
Neutrophils=55% (Normal: average range: 50-65%)
Monocytes= 15% (Abnormal: with a average range of 2-9%)
CD4 T cells= 20% (Normal: with an average of 20%)
CD8 T cells= 9% (Top end of the range: with an average 10%)
B cells= 10% (Top end of the range: with an average range of 10-15%)

The immune system was not functioning properly.

5 of 15

ELISA and Lymph node biopsy analysis

We wanted to run an ELISA (Enzyme-Linked Immunosorbent Assay) to measure antibodies in the patients blood.

We also conducted a lymph node biopsy to look at the phagocytes and specific bacteria because the patient had recurrent bacterial infections.

Antibody	Patient Serum antibody levels (mg/dl)	Range for Normal Serum Antibodies
IgM	175	75-150
IgA	450	150-225
IgG	1750	600-1500

6 of 15

Flow Cytometry

We wanted to measure if a Th1 response was present. The flow cytometry showed normal levels of CD40 and CD40L.

7 of 15

ELISA for IFNgR PBMCs and IFNg response

We then ran another Flow Cytometry and a ELISA to determine if the Interfering gamma (IFNg) and Interfering gamma receptor (IFNgR) was deficient.

Lower IFN-yR: Receptor

8 of 15

TH1 activates macrophages

Intracellular Bacteria

9 of 15

DNA Sequencing and Western Blot

DNA sequencing: is used to show changes in patients DNA.

Frameshift Deletion in DNA (TCTAGT) causing a nucleotide shift.

Western Blot: is used to show proteins present in mixtures extracted from cells.

No protein levels of IFN-R1

10 of 15

Diagnosis

The diagnosis was confirmed through DNA Sequencing and Western Blots that showed a deficiency in the IFN-gamma receptor 1.

11 of 15

Background Information

Prevalence: IFN-g receptor 1 deficiency is considered a rare disease. Approximately 1 to 8,000 people in the world and 1 to 300 people in USA.
Symptoms: Symptoms appear in newborns to infants. Symptoms might included abnormal bronchitis physiology, anemia, anorexia, diarrhea, and enlarged lymph nodes.

Description: IFN-g receptor 1 is not present within the patient. Without IFN-g receptor 1 the cytokines cannot bind and activate immune cells.
Similar Immunodeficiencies based on similar gene descriptors.

Immunodeficiency 27a: 32.4% in common.
Osteomyelitis: 30.1% in common.
Mycobacterium Tuberculosis 1 (TB): 29.5% in common.

Tris:

Symptoms are not clean with many resources, there are 10 different types of deficiency of IFN-g 1 and IFN-g 2.

IFN-g primarily secreted by activated T cells and NK cells to promote macrophage activation, enhance antigen presentation, mediate antiviral and antibacterial immunity, regulate Th1/Th2 balance, and helps activate the innate immune response.

The Similar immunodeficiencies where found by malacards using their database, in which they compare immunodeficiencies based on symptoms, gene desprictors, and causes.

Just in case people ask what the the other immunodeficiencies are:

Immunodeficiency 27a results from autosomal recessive (AR) IFNGR1 deficiency. Osteomyelitis is bone infection, often caused by a bacterial infection, although it can also be caused by a fungal infection. Mycobacterium Tuberculosis 1 caused by bacteria called Mycobacterium tuberculosis. The bacteria usually attack the lungs, but they can also damage other parts of the body. TB spreads through the air when a person with TB of the lungs or throat coughs, sneezes, or talks. If you have been exposed, you should go to your doctor for tests. All other similar immunodeficiencies have some type of deficiency with the IFN-g receptor.

12 of 15

Therapy Options

Homologous Stem Cell Transplantation

Bone marrow from the patient is removed and is genetically modified and then is given back to the patient.

VS

Bone Marrow Transplant

Where bone marrow is taken from a healthy individual and give it to the patient.

13 of 15

Preferred Therapy for Patient

Homologous Stem Cell Transplantation

Reasons Why:

Chance of rejection with traditional bone marrow transplant.
The ability of generate of their own IFN-g receptors with Homologous Stem Cell Transplant.

14 of 15

Questions?

15 of 15

RESOURCES

Gutierrez, M. J., Kalra, N., Horwitz, A., & Nino, G. (2016). Novel Mutation of Interferon-γ Receptor 1 Gene Presenting as Early Life Mycobacterial Bronchial Disease. Journal of investigative medicine high impact case reports, 4(4), 2324709616675463. https://doi.org/10.1177/2324709616675463
McKinnon, Katherine M. “Flow Cytometry: An Overview.” Current Protocols in Immunology, U.S. National Library of Medicine, 21 Feb. 2018, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5939936/.
U.S. Department of Health and Human Services. (2021, November 8). Interferon gamma, receptor 1, deficiency - about the disease. Genetic and Rare Diseases Information Center. Retrieved March 20, 2022, from https://beta.rarediseases.info.nih.gov/diseases/3011/interferon-gamma-receptor-1-deficiency
Interferon Gamma, Receptor 1, Deficiency. Malacards.org. (n.d.). Retrieved March 27, 2022, from https://www.malacards.org/card/interferon_gamma_receptor_1_deficiency?search=Interferon+Gamma%2C+Receptor+1%2C+Deficiency