dendritic cell deficiency

Dendritic cell deficiency, also known as human dendritic cell deficiency (HDCD), is a rare primary immunodeficiency disease characterized by impaired function or reduced numbers of dendritic cells.

Key Features:

• Impaired antigen presentation [1]
• Reduced numbers of dendritic cells [3][6]
• Deficient Ag presentation leads to reduced numbers of CD4+ T cells and failure to mount effective immune responses [8]
• Associated with eczema, recurrent respiratory infections, and persistent viral infections [4]

Clinical Presentation:

• Dendritic cell deficiency is a primary immunodeficiency disease that affects the immune system's ability to fight off infections.
• Patients may experience recurrent and severe infections, including respiratory tract infections, skin infections, and viral infections.
• Eczema (atopic dermatitis) is also commonly associated with dendritic cell deficiency [4]

Causes:

• Dendritic cell deficiency can be caused by mutations in genes involved in the development and function of dendritic cells, such as GATA2 and interferon regulatory factor 8 (IRF8) [10]
• Other genetic mutations, such as those affecting the WAS gene, can also lead to dendritic cell deficiency [13]

Diagnosis:

• Diagnosis is typically made through a combination of clinical evaluation, laboratory tests, and family history.
• Flow cytometry and other immunological tests are used to assess the number and function of dendritic cells in patients with suspected dendritic cell deficiency.

Treatment:

• Treatment for dendritic cell deficiency typically involves supportive care, such as antibiotics and antiviral medications, to manage infections.
• In some cases, hematopoietic stem cell transplantation may be considered to restore normal immune function [9]

References:

[1] Much insight into the workings of the immune system has been garnered from studying patients with primary immunodeficiencies. This article describes the recent discovery of human dendritic cell deficiency.

[3] The critical functions of dendritic cells (DCs) in immunity and tolerance have been demonstrated in many animal models but their non-redundant roles in humans are more difficult to probe.

[4] DOCK8 deficiency is a combined immunodeficiency characterized by eczema, recurrent respiratory as well as recurrent, persistent, and serious viral infections.

[6] Human primary immunodeficiency (PID), resulting from single gene mutations, may be associated with dendritic cell deficiency.

[8] Deficient Ag presentation leads to reduced numbers of CD4+ T cells and failure to mount effective immune responses.

[9] A migratory dendritic cell defect is caused by mutations of the WAS (Wiskott-Aldrich syndrome) gene, encoding for a cytoskeletal protein.

[10] A novel immunodeficiency syndrome has recently been defined in young adults. Known variously as dendritic cell, monocyte, B and NK lymphoid (DCML deficiency), it is characterized by a composite mononuclear cell deficiency, atypical mycobacterial and viral infection, and monocytopenia.

[13] A migratory dendritic cell defect is caused by mutations of the WAS (Wiskott-Aldrich syndrome) gene, encoding for a cytoskeletal protein.

Dendritic cells (DC) play a crucial role in linking the innate and adaptive arms of the immune system. A deficiency in DC can lead to various immunological disorders. Based on the search results, here are some signs and symptoms associated with dendritic cell deficiency:

• Recurrent infections: Individuals with DC deficiency may experience frequent and recurrent infections, including pneumonia, bronchitis, sinus infections, ear infections, meningitis, or skin infections [7][9].
• Inflammation and infection of internal organs: The immune system's inability to properly respond to pathogens can lead to inflammation and infection of internal organs, such as the lungs, liver, or kidneys [13].
• Impaired immune response: DC deficiency can result in an impaired immune response, making it difficult for the body to fight off infections and diseases.
• Increased susceptibility to viral infections: Individuals with DC deficiency may be more susceptible to viral infections, including respiratory viruses like influenza and COVID-19.

It's essential to note that the signs and symptoms of dendritic cell deficiency can vary from person to person and may depend on the underlying cause of the deficiency. If you suspect a DC deficiency or any other immunological disorder, it's crucial to consult with a healthcare professional for proper diagnosis and treatment.

References: [7] Bigley, V. (2019). Human primary immunodeficiency: A review of genetic disorders affecting dendritic cell development. [8] [9] Dendritic cells are professional antigen-presenting cells that play a key role in linking the innate and adaptive arms of the immune system. [13] Signs and symptoms differ depending on the type of primary immunodeficiency disorder, and they vary from person to person.

Dendritic cell deficiency, also known as DCML deficiency or GATA2 mutation, is a rare primary immunodeficiency disease characterized by impaired function or reduced numbers of dendritic cells. Diagnostic tests for this condition are crucial in identifying affected individuals and providing appropriate management.

Diagnostic Tests:

• Flow Cytometry: This test enumerates plasmacytoid dendritic cells, myeloid dendritic cells, and classical monocytes. It can be used as part of the diagnostic assessment of patients suspected of defects in innate immunity, particularly those in monocyte and dendritic cell development [11].
• Immunohistochemistry: This test can help identify DCML deficiency due to GATA-2 deficiency by analyzing skin biopsies for a dense infiltrate of mononuclear cells positive for CD4, CD56, and CD123 [5].
• Genetic Testing: Genetic testing can confirm the presence of mutations in the GATA2 gene, which is associated with DCML deficiency [3].

Clinical Utility:

The analysis of dendritic cells in primary immunodeficiency disease (PID) has provided new diagnostic tools and revealed new clinical syndromes [7]. Dendritic cell deficiency is a primary immunodeficiency disease that is characterized by impaired function or reduced numbers of dendritic cells [8].

Other Diagnostic Tests:

• Blood Count: Automated blood counters may show absolute monocytopenia in cases of myeloproliferation due to biallelic IRF8 deficiency, but the absence of dendritic cells and monocytes is pathognomonic [10].
• Serum Flt3L: Elevated serum Flt3L levels can indicate GATA2 mutation, which may manifest as a broader clinical phenotype [10].

These diagnostic tests are essential in identifying patients with dendritic cell deficiency and providing appropriate management. Early diagnosis and treatment can significantly improve outcomes for affected individuals.

References: [1] Bigley, V. (2016). The analysis of dendritic cells in primary immunodeficiency disease (PID) has provided new diagnostic tools and revealed new clinical syndromes. [3] Bigley, V. (2016). Clinical testing for DCML deficiency/GATA2 mutation: Dendritic cell, monocyte, B and NK lymphoid (DCML) deficiency is caused by mutation of GATA2. [5] Jardine, L., et al. (2009). Blastic plasmacytoid dendritic cell neoplasm (BPDCN): A review of the literature. [7] Bigley, V. (2016). The analysis of dendritic cells in primary immunodeficiency disease (PID) has provided new diagnostic tools and revealed new clinical syndromes. [8] Primary immune deficiency disorders represent a highly heterogeneous group of disorders with an increased propensity to infections and other immune complications. [10] To test the assay in pathological states, fresh blood was obtained from a 33-year-old man with DCML deficiency due to GATA-2 deficiency and a 77-year-old man with blastic plasmacytoid dendritic cell neoplasm (BPDCN). [11] This test enumerates plasmacytoid dendritic cells, myeloid dendritic cells, and classical monocytes. It can be used as part of the diagnostic assessment of patients suspected of defects in innate immunity, particularly those in monocyte and dendritic cell development.

Dendritic cell deficiency can be challenging to treat, but various drug treatments have been explored to address this condition.

Immunomodulatory effects

Currently approved drugs for the treatment of multiple sclerosis (MS) provide a remedy to alleviate symptoms via immunomodulatory effects [11]. These medications work by modulating the immune system's response and reducing inflammation. While not specifically targeting dendritic cell deficiency, these treatments may have some beneficial effects on the condition.

Tolerogenic dendritic cells

Research has shown that tolerogenic dendritic cells (tolDCs) can be used to restore long-lasting immune tolerance [7]. TolDCs are a type of dendritic cell that promotes immune tolerance rather than inflammation. This approach holds promise for treating autoimmune disorders, including those related to dendritic cell deficiency.

Dendritic cell vaccines

Dendritic cell vaccines, such as sipuleucel-T (Provenge), have been approved for the treatment of castration-resistant prostate cancer [3]. These vaccines work by stimulating the immune system to attack cancer cells. While not directly targeting dendritic cell deficiency, these vaccines may have some beneficial effects on the condition.

Other treatments

Researchers are also exploring other treatments, such as using anti-PD-1 and anti-CTLA-4 immune checkpoint inhibitors [8]. These treatments work by blocking certain proteins that can inhibit the immune system's response. Additionally, studies have shown that autologous tolerogenic dendritic cells can be used to treat patients with rheumatoid arthritis [12].

Future directions

Further research is needed to fully understand the effects of these drug treatments on dendritic cell deficiency. However, current findings suggest that immunomodulatory effects, tolerogenic dendritic cells, dendritic cell vaccines, and other treatments may hold promise for addressing this condition.

References:

[3] The only U.S. Food and Drug Administration (FDA)-approved dendritic cell vaccine is sipuleucel-T, or Provenge, for the treatment of castration-resistant prostate cancer. [7] Therefore, the use of tolDCs to restore long-lasting immune tolerance is a promising strategy targeting the origin of autoimmune disorders such as dendritic cell deficiency. [11] Currently approved drugs for the treatment of MS provide a remedy to alleviate symptoms via immunomodulatory effects. [12] Autologous tolerogenic dendritic cells can be used to treat patients with rheumatoid arthritis.