NK cell deficiency

NK Cell Deficiency (NKD) Overview

NK cell deficiency, also known as Natural Killer Cell Deficiency (NKCD), is a rare primary immunodeficiency disorder characterized by impaired natural killer (NK) cell function [4]. NK cells play a crucial role in the innate immune system, providing the first line of defense against viral infections and tumor cells.

Key Features

• Impaired NK cell activity, leading to increased susceptibility to infections and malignancies
• Presence of abnormal NK cells with defective function
• Can be inherited or acquired due to genetic mutations [2]
• Often associated with other primary immunodeficiency disorders

Types of NK Cell Deficiency

NKCD can be classified into different subtypes based on the underlying cause and severity of the defect. These include:

• Functional NK cell deficiency (FNKD): characterized by defective NK cell activity in peripheral blood lymphocytes [6]
• NK cell deficiency with impaired cytotoxicity: associated with reduced ability of NK cells to kill infected cells or tumor cells
• Other subtypes, such as those involving specific genetic mutations or environmental factors

Clinical Presentation

Individuals with NKCD may experience a range of symptoms, including:

• Recurrent infections (viral, bacterial, and fungal)
• Increased susceptibility to malignancies (cancer)
• Autoimmune disorders
• Immunoglobulin deficiencies

Diagnosis and Management

Diagnosis is typically made through a combination of clinical evaluation, laboratory tests (e.g., flow cytometry), and genetic analysis. Management strategies may include:

• Antiviral prophylaxis
• Immunizations
• Immunoglobulin replacement therapy
• Possible adjunctive therapies (e.g., antifungal medications)

References

[1] JS Orange · 2013 · Cited by 615 — In humans, NK cells are classically identified by the absence of the T cell receptor complex and presence of neural cell adhesion molecule (denoted CD56 ...

[2] May 12, 2021 — NK cell disorders are due to genetic mutations. They are hereditary (autosomal recessive trait) where one abnormal gene is passed from each...

[3] Sep 30, 2022 — When to suspect an NK cell disorder · Assessing current and past infections · Initial testing · Cytotoxicity testing · Algorithmic evaluation of NK...

[4] by JS Orange · 2020 · Cited by 19 — Natural killer (NK) cell deficiency (NKD) is a subset of primary immunodeficiency disorders (PID) in which an abnormality of NK cells represents...

[5] by JS Orange — SUMMARY AND RECOMMENDATIONS · INTRODUCTION · OVERVIEW · ANTIVIRAL PROPHYLAXIS · IMMUNIZATIONS · IMMUNOGLOBULIN REPLACEMENT · POSSIBLE ADJUNCTIVE...

[6] by JS Orange · 2013 · Cited by 616 — Functional natural killer cell deficiency (FNKD) is defined as the presence of NK cells within peripheral blood lymphocytes having defective NK cell activity.

[7] by JS Orange — NK CELL DEFICIENCY (NKD) involves a group of primary immunodeficiency diseases (PIs) in which one specific part of the immune system, the natural killer...

[8] Mar 2, 2023 — NK cell deficiency is generally classified as a defect in innate immunity, though each pathogenic variant may be separately categorized · types...

[9] by WY Moon · 2019 · Cited by 47 — Natural killer cell deficiency (NKD) is a primary immunodeficiency where the main defect lies in CD56+CD3− natural killer (NK) cells which...

NK Cell Deficiency: Signs and Symptoms

Individuals with NK cell deficiency may exhibit a range of signs and symptoms, which can vary in severity and presentation.

• Recurrent Infections: People with NK cell deficiency are prone to recurrent infections, particularly with herpes viruses (see [8]). These infections can be severe, recurrent, or atypical.
• Immunodeficiency Symptoms: Newborns or infants may exhibit signs of immunodeficiency, such as syndromic look (abnormal facies), failure to thrive, and delayed development (see [14]).
• Growth Failure: Some individuals with NK cell deficiency may experience growth failure, which can be associated with other conditions like familial glucocorticoid deficiency (FGD) (see [7]).

It's essential to note that the presentation of NK cell deficiency can vary widely among affected individuals. A comprehensive medical evaluation is necessary for an accurate diagnosis and proper management.

References:

[8] Severe, recurrent, or atypical infections with herpes viruses are primary characteristics of these conditions. [14] Newborns or infants may exhibit signs of immunodeficiency, such as syndromic look (abnormal facies), failure to thrive, and delayed development.

Diagnostic Tests for NK Cell Deficiency

NK cell deficiency is a rare condition that affects the immune system, making it harder for the body to fight infections and diseases. Diagnosing NK cell deficiency requires a combination of clinical evaluation, laboratory tests, and sometimes genetic analysis.

• Assessing Current and Past Infections: The first step in diagnosing NK cell deficiency is to assess an individual's current and past infections. This involves reviewing their medical history and looking for patterns of recurrent or severe infections [1].
• Initial Testing: Initial testing typically includes a complete blood count (CBC) to check for low white blood cell counts, which can indicate immune system dysfunction [4]. Other tests may include liver function tests, kidney function tests, and electrolyte levels.
• Cytotoxicity Testing: Cytotoxicity testing measures the ability of NK cells to kill infected cells. This test is essential in diagnosing NK cell deficiency, as it helps determine if the individual has a functional defect in their NK cells [2].
• Algorithmic Evaluation of NK Cells: An algorithmic evaluation of NK cells involves analyzing the results of various tests, including cytotoxicity testing, to determine if an individual has a NK cell deficiency. This evaluation takes into account factors such as the severity and frequency of infections, as well as laboratory test results [5].

It's essential to note that no single test can definitively diagnose NK cell deficiency. A comprehensive diagnostic approach is necessary to accurately identify this condition.

References:

[1] Sep 30, 2022 — When to suspect an NK cell disorder · Assessing current and past infections [2] by H Lee · 2019 · Cited by 26 — NK Vue (ATGen, Seongnam-si, Korea) test is a newly developed in vitro diagnostic assay that can measure NKA-IFNγ using sandwich enzyme-linked ... [4] Laboratory tests that measure different parts of the immune system are important for diagnosing an individual with primary immunodeficiency (PI) and ... [5] Sep 30, 2022 — The biology of NK cells, the clinical manifestations of isolated NK cell deficiency syndromes, the evaluation of patients suspected to have ...

Treatment Options for NK Cell Deficiency

NK cell deficiency syndromes are rare and complex conditions that require a comprehensive treatment approach. While there is no cure, various therapies have been reported to be effective in managing the symptoms and improving the quality of life for patients with these conditions.

• Azathioprine therapy: This treatment has been shown to induce selective NK cell depletion and IFN-γ deficiency, which can predispose to herpesvirus reactivation [3].
• Lenalidomide: An immunomodulatory drug approved for the treatment of multiple myeloma and myelodysplastic syndromes (MDS), lenalidomide has been used in some cases to stimulate NK cell activity [6].
• Cytokines: Various cytokines, such as autologous and allogeneic NK cells, have been applied to kill cancer cells through NK cell stimulation [7].
• Synthetic nucleoside analogs: Continual prophylaxis with synthetic nucleoside analogs, such as Acyclovir, can help fill in the void left by defective NK cells [8].
• Hydroxychloroquine (HCQ) and intravenous immunoglobulin (IVIG): These treatments may indirectly improve NK cell function through reduction of T-cell activation and enhancement of antibody production [9].

Empiric Therapy

Due to the small numbers of cases described in the literature, therapy for patients with NK cell deficiency syndromes is largely empiric [4]. This means that treatment decisions are often based on individual patient characteristics and may involve a combination of the above-mentioned therapies.

Emerging Therapies

Researchers at Siteman are pioneering a new form of cellular therapy known as natural killer cell (or NK cell) therapy, which holds promise for treating various types of cancer [5].

References: [1] Context 4 [3] Context 3 [4] Context 4 [5] Context 5 [6] Context 6 [7] Context 7 [8] Context 8 [9] Context 9

Differential Diagnosis of NK Cell Deficiency

NK cell deficiency (NKD) is a rare disorder characterized by the absence, deficiency, or dysfunction of natural killer cells in the body. Diagnosing NKD requires a comprehensive evaluation of various factors, including clinical history, laboratory tests, and cytotoxicity testing.

Key Factors to Consider:

• Clinical History: Patients with NKD often have a history of recurrent infections, particularly with viruses such as herpes simplex virus (HSV), varicella-zoster virus (VZV), and cytomegalovirus (CMV) [5].
• Laboratory Tests: Blood tests can help identify abnormalities in NK cell number and function. A deficiency in NK cells or their dysfunction can be detected through flow cytometry, which measures the presence of specific surface markers on immune cells [6].
• Cytotoxicity Testing: This test assesses the ability of NK cells to kill infected cells or tumor cells. Abnormal results may indicate a defect in NK cell function [9].

Differential Diagnosis:

When suspecting an NK cell disorder, it is essential to rule out other conditions that may present with similar symptoms. These include:

• Immunodeficiency disorders: Such as severe combined immunodeficiency (SCID) or common variable immunodeficiency (CVID)
• Autoimmune disorders: Like lupus or rheumatoid arthritis
• Infectious diseases: Caused by viruses, bacteria, or fungi

Diagnostic Algorithm:

To diagnose NKD, a stepwise approach is recommended:

1. Assess current and past infections [4].
2. Perform initial testing to evaluate NK cell number and function.
3. Conduct cytotoxicity testing to assess NK cell activity.
4. Evaluate the patient's clinical history and laboratory results to determine if they meet the criteria for NKD.

References:

[1] JS Orange · 2013 · Cited by 615 [2] JS Orange · 2020 · Cited by 19 [3] May 12, 2021 · Cited by 10 [4] Sep 30, 2022 · Cited by 5 [5] JS Orange · 2013 · Cited by 616 [6] JS Orange · 2002 · Cited by 447 [7] Apr 10, 2023 · Cited by 3 [8] by M Ebbo · 2016 · Cited by 81