CD45 deficiency

CD45 deficiency is a severe combined immunodeficiency disease that affects both T and B lymphocytes, leading to impaired immune function.

Key Features:

• Severe Combined Immunodeficiency (SCID): CD45 deficiency results in SCID due to the dysfunction of both T and B lymphocytes [3][7].
• T- and B-lymphocyte Dysfunction: The disease leads to a marked impairment in T cell development, resulting in severe combined immune deficiency [2][4].
• Autoimmune Diseases: CD45 deficiency also plays a significant role in autoimmune diseases due to the dysfunction of both T and B lymphocytes [4].

Causes:

• Uniparental Disomy (UPD): Disease was caused by uniparental disomy with isodisomy of the entire maternal Chr1 bearing the mutant CD45 allele [1].
• Autosomal Recessive Inheritance: The disease follows an autosomal recessive inheritance pattern, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the condition [3].

Symptoms:

• Pyogenic Arthritis: Patients with CD45 deficiency may present with pyogenic arthritis and other symptoms related to impaired immune function.

Note: The above information is based on the search results provided in the context.

CD45 deficiency, also known as severe combined immunodeficiency (SCID), is characterized by a combination of symptoms that affect the immune system.

• Low to absent T cells: The most common manifestation of SCID is a significant reduction or complete absence of T cells in the blood [4].
• Infection and failure to thrive: Infected individuals may experience persistent respiratory tract infections, fever, diarrhea, dermatitis, and failure to gain weight or grow at a normal rate [8].
• Lymphadenopathy and hepatosplenomegaly: Some patients may have swollen lymph nodes (lymphadenopathy) and an enlarged spleen (hepatosplenomegaly) [5].
• Oral thrush and other symptoms: Manifestations may also include oral thrush, a fungal infection that causes white patches on the tongue and inside the cheeks [5].

It's worth noting that some patients with CD45 deficiency may have neurological signs, including cortical blindness and dystonia, although this is less common [3].

Based on the provided context, here are some diagnostic tests that can be used to identify CD45 deficiency:

• Flow cytometry: This test can help analyze leucocyte subsets and function, which is essential in diagnosing immunodeficiency disorders like SCID (Severe Combined Immunodeficiency) [2].
• SNP arrays and whole-exome sequencing: These genetic tests can be used to identify the cause of SCID in a patient known to lack the protein-tyrosine phosphatase CD45 [1, 3].
• Complete blood count (CBC): A CBC with differential can help detect lymphopenia, which is a characteristic feature of SCID. Children with SCID typically have a lymphocyte count lower than 3000/μL [9].
• Immunoglobulin levels: Measuring immunoglobulin levels is essential in evaluating specific humoral and cellular immunity in patients suspected to have SCID [5].

These diagnostic tests can help identify CD45 deficiency, which is associated with SCID. It's worth noting that a newborn screening blood test can also show if a baby has a low number of T cells, a sign that may indicate SCID [7].

Based on the provided context, it appears that there are several potential treatment options for CD45 deficiency.

• Bone Marrow Transplantation: According to search result 1, bone marrow transplantation has been successfully used to treat SCID (Severe Combined Immunodeficiency), a condition related to CD45 deficiency.
• CD45-replacement gene therapy: Search result 8 proposes the development of a CD45-replacement gene therapy to correct the genetic deficiency in patients with CD45 deficiency. This approach aims to replace the faulty CD45 gene with a functional one, potentially leading to improved immune function.
• Conditioning with anti-CD45 ADCs: Search result 5 suggests that conditioning with anti-CD45 antibody-drug conjugates (ADCs) may represent a novel and safe conditioning regimen for patients with RAG deficiency and other inborn errors of immunity, including CD45 deficiency. This approach involves using targeted therapy to prepare the patient's body for transplantation.
• Hematopoietic stem cell transplantation: Search result 7 mentions hematopoietic stem cell transplantation (HSCT) as a widely used treatment option for patients with life-threatening hematologic and immune system disorders, including CD45 deficiency.

It is essential to note that these treatment options may have varying degrees of success and potential side effects. A comprehensive discussion with a medical professional would be necessary to determine the most suitable course of action for an individual patient.

References: * [1] JL Roberts · 2012 · Cited by 51 * [5] by MC Castiello · 2021 · Cited by 36 * [7] by VM Stepanova · 2024 * [8] (proposed treatment option)

CD45 deficiency is a rare genetic disorder that affects the immune system, leading to severe combined immune deficiency (SCID). The differential diagnosis of CD45 deficiency involves considering other conditions that may present with similar symptoms.

Key Features of CD45 Deficiency:

• Severe impairment in T cell development [1]
• Pyogenic arthritis and recurrent infections [1]
• Lymphocyte dysfunction, leading to SCID [4]

Other Conditions to Consider in the Differential Diagnosis:

• SCID due to other genetic mutations: Other genes involved in immune function, such as JAK3, IL2RG, and ADA, can also lead to SCID. These conditions may present with similar symptoms, including recurrent infections and lymphocyte dysfunction [4].
• Autoimmune disorders: Conditions like autoimmune hemolytic anemia, autoimmune thrombocytopenia, and autoimmune nephritis can also present with lymphoproliferation and autoantibody production, similar to CD45 deficiency [7].
• Immunodeficiency due to other causes: Other factors, such as viral infections (e.g., HIV), chemotherapy, or radiation therapy, can also lead to immunodeficiency and SCID-like symptoms.

Diagnostic Criteria:

To diagnose CD45 deficiency, clinicians should consider the following criteria:

• Severe impairment in T cell development
• Presence of pyogenic arthritis and recurrent infections
• Lymphocyte dysfunction leading to SCID

References:

[1] A deficiency of CD45 leads to a marked impairment in T cell development. The diagnosis should be suspected in patients presenting with pyogenic arthritis and ...

[4] by A Rheinländer · 2018 · Cited by 265 — CD45 deficiency results in T- and B-lymphocyte dysfunction in the form of severe combined immune deficiency.

[7] by R Majeti · 2000 · Cited by 317 — The CD45 E613R mutation causes polyclonal lymphocyte activation leading to lymphoproliferation and severe autoimmune nephritis with autoantibody production, ...