MHC class I deficiency

MHC class I deficiency, also known as Bare Lymphocyte Syndrome type I (BLS-I), is a rare autosomal recessive disease that affects the immune system.

Key Features:

• Primary Immunodeficiency: MHC class I deficiency is a primary immunodeficiency disorder, meaning it arises from a genetic mutation affecting the major histocompatibility complex (MHC) class I proteins.
• Rare Disease: This condition is extremely rare and has been reported in less than 30 patients worldwide [3].
• Inherited Pattern: MHC class I deficiency is inherited in an autosomal recessive pattern, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the condition.
• Immune System Compromise: The disease compromises both innate and adaptive immune systems due to the absence or dysfunction of MHC class I molecules [5].

Symptoms:

• Recurrent Infections: People with MHC class I deficiency often experience recurrent infections, particularly in the first year of life [4].
• Pneumonitis, Bronchitis, Gastroenteritis: Common symptoms include pneumonitis, bronchitis, gastroenteritis, and septicemia.
• Chronic Bacterial Sinobronchial Infections: MHC class I deficiency-1 (MHC1D1) is characterized by the onset of recurrent and chronic bacterial sinobronchial infections [8].

Clinical Features:

• Milder than MHC Class II Deficiency: MHC class I deficiency is typically milder than MHC class II deficiency.
• Variable Severity: The severity of the disease can vary among affected individuals.

Overall, MHC class I deficiency is a rare and complex immunodeficiency disorder that requires careful management to prevent recurrent infections and other complications.

MHC class I deficiency, also known as Bare Lymphocyte Syndrome (BLS) type 1, is a rare primary immunodeficiency characterized by the severe reduction or absence of MHC class I molecules on the surface of cells. While most people with this condition are asymptomatic during childhood, they may develop symptoms later in life.

Common Symptoms:

• Recurrent bacterial infections of the respiratory tract [3]
• Granulomatous skin lesions (in about half of the cases) [6]
• Decreased CD4+ T cell numbers and impaired functions due to the absence of MHC class II molecules on the surfaces of the cells [9]

Other Possible Symptoms:

• Frequent upper respiratory tract infections, such as sinusitis or bronchitis [10]
• Increased susceptibility to viral infections
• Skin

Diagnostic Tests for MHC Class I Deficiency

MHC Class I deficiency can be diagnosed through various tests, which are essential for a definitive diagnosis.

• Absence of MHC Class 1 Proteins: A definite diagnosis can be made by looking for the absence of MHC class 1 proteins on the surface of peripheral blood mononuclear cells [3].
• Genetic Testing: Further genetic testing is then conducted to confirm the diagnosis. This involves analyzing the genes responsible for encoding TAP1, TAP2, and TAPBP [1].
• Serologic HLA Typing: Although less commonly used today, serologic HLA typing was previously employed to diagnose HLA class I deficiency [9].

These diagnostic tests are crucial in identifying MHC Class I deficiency, a rare autosomal recessive primary immunodeficiency characterized by reduced cell surface expression of HLA class I molecules.

References: [1] Clinical resource with information about MHC class I deficiency and its clinical features, TAP1, TAP2, TAPBP, available genetic tests from US and labs ... [3] A definite diagnosis can be made by looking for MHC class 1 proteins on the surface of peripheral blood mononuclear cells. Further genetic testing is then ... [9] by S Hanna · 2014 · Cited by 146 — Until recently, HLA class I deficiency was diagnosed by means of serologic HLA typing. However, with the decreased use of serologic testing for ''routine'' HLA ...

Current Treatment Options for MHC Class I Deficiency

MHC class I deficiency, also known as Bare Lymphocyte Syndrome Type 1 (BLS1), is a rare genetic disorder characterized by impaired T-cell immunity and increased susceptibility to infections. While there is no specific cure for this condition, various treatment options are available to manage the symptoms and prevent complications.

• Antimicrobial Therapy: The mainstay of therapy for MHC class I deficiency is aggressive treatment of infections with appropriate antimicrobial agents [5]. This approach helps control bacterial, viral, and fungal infections that can arise due to the compromised immune system.
• IVIG Therapy: Some patients have benefitted from the use of Intravenous Immunoglobulin (IVIG) therapy, which provides antibodies to help combat infections [5].
• Hematopoietic Cell Transplantation (HCT): Hematopoietic cell transplantation remains the only curative treatment for MHC class I deficiency, but transplant survival in previously affected individuals is a significant concern [9].

Emerging Therapeutic Strategies

Recent studies have explored new therapeutic approaches to address MHC-I epigenetic silencing and antigen presentation in tumor cells. Histone deacetylase inhibitors (HDACi) have been shown to reverse MHC-I epigenetic silencing, potentially offering a novel treatment avenue [3].

Current Limitations and Future Directions

While these treatment options can help manage the symptoms of MHC class I deficiency, there is still no specific therapy that can cure this condition. Further research is needed to develop more effective treatments and improve patient outcomes.

References:

[1] Gao Y et al. (2016) - Bone marrow transplantation for MHC class I deficiency corrects T-cell immunity but dissociates natural killer cell repertoire formation from function. [3] Shklovskaya E et al. (2021) - MHC-I epigenetic silencing due to histone deacetylation can be reversed with histone deacetylase inhibitors (HDACi). [5] Hanna S et al. (2014) - Treatment and prognosis. [9] Lum SH et al. (2020) - Hematopoietic cell transplantation (HCT) remains the only curative treatment for this condition, but transplant survival in previously affected individuals is a significant concern.

Differential Diagnosis of MHC Class I Deficiency

MHC Class I deficiency, also known as Bare Lymphocyte Syndrome Type 1, is a rare autosomal recessive primary immunodeficiency characterized by reduced cell surface expression of HLA Class I molecules. When diagnosing this condition, it's essential to consider the differential diagnosis, which includes other conditions that may present with similar symptoms.

Conditions to Consider in Differential Diagnosis:

• Chronic granulomatous disease
• Common variable immunodeficiency
• Granulomatosis with polyangiitis
• Sarcoidosis

These conditions can be considered in the differential diagnosis of MHC Class I deficiency, particularly when patients present with symptoms such as recurrent upper respiratory infections and resultant complications (1). However, it's crucial to note that MHC Class I deficiency is typically milder than other forms of immunodeficiency, such as MHC Class II deficiency (3).

Key Features to Distinguish MHC Class I Deficiency:

• Reduced cell surface expression of HLA Class I molecules
• Typically milder symptoms compared to other forms of immunodeficiency
• Rare autosomal recessive primary immunodeficiency

When considering the differential diagnosis for patients with suspected MHC Class I deficiency, it's essential to keep these key features in mind and rule out other conditions that may present with similar symptoms.

References:

[1] - Search result 9: "The differential diagnosis for patients who present with recurrent upper respiratory infections, resultant..."

[3] - Search result 3: "This immunodeficiency is typically milder than the more severe MHC class II deficiency."

Note: The numbers in square brackets refer to the search results provided in the context.