What is primary combined immunodeficiency? What are its classifications?

Primary combined immunodeficiency disease (PCID) is a hereditary immunodeficiency disorder, mostly inherited in an autosomal recessive manner, involving both antibody and cellular immune deficiencies.

It can be further classified into severe combined immunodeficiency (SCID), immunodeficiency with thrombocytopenia and eczema (also known as Wiskott-Aldrich syndrome), ataxia-telangiectasia, and cellular immunodeficiency with abnormal immunoglobulin synthesis (also known as Nezelof syndrome).

SCID typically manifests early in life with severe clinical symptoms and a poor prognosis, posing a serious threat to children's health.

Which department should be consulted for primary combined immunodeficiency?

English name: Primary combined immunodeficiency disease.

Aliases: Combined immunodeficiency disease, CID, primary combined immunodeficiency disease.

Departments to visit: Rheumatology and Immunology, Pediatrics, Hematology.

What causes primary combined immunodeficiency?

It may be related to congenital teratogenic factors, such as bone marrow hematopoietic stem cell dysplasia.

Most cases are caused by autosomal or sex-linked recessive genetic factors, such as SCID and Wiskott-Aldrich syndrome. These patients exhibit both cellular immune dysfunction (simply understood as defective "soldiers" in immune defense) and humoral immune dysfunction (i.e., antibody-related issues).

In cases of cellular immunodeficiency with abnormal immunoglobulin synthesis, there is a reduction in lymphocytes and lymphoid tissues, abnormal thymic structure, and varying levels of immunoglobulins in the serum.

Which populations are commonly affected by primary combined immunodeficiency?

SCID predominantly affects children, usually manifesting between 2 to 7 months after birth. Eczema symptoms often appear around 1 year of age and are more common in males.

Ataxia-telangiectasia may develop between 9 to 12 months of age or as late as 4 to 6 years.

Cellular immunodeficiency with abnormal immunoglobulin synthesis occurs sporadically, with no gender difference.

What are the common symptoms of primary combined immunodeficiency?

1. SCID:

• Infections often appear within 3 months after birth, including recurrent pneumonia, chronic diarrhea, fungal infections of the mouth and skin, and otitis media. It may also be accompanied by bone dysplasia, leading to dwarfism.

2. Immunodeficiency with thrombocytopenia and eczema:

• Mostly affects males, with bleeding as the initial symptom. Infections become frequent after 6 months, and malignant diseases may develop after the age of 10.

3. Ataxia-telangiectasia:

• Ataxia typically appears between 9 to 12 months. Most patients experience intellectual developmental delays, and some may develop insulin-dependent diabetes. Lymphoreticular malignancies and other tumors are common complications.

4. Cellular immunodeficiency with abnormal immunoglobulin synthesis:

• Mainly presents as recurrent infections, including Pneumocystis carinii pneumonia and rubella virus infections. Lymphadenopathy and chronic pulmonary fungal infections may also occur.

How is primary combined immunodeficiency diagnosed?

• SCID is diagnosed based on clinical manifestations like recurrent infections and laboratory tests.
• Immunodeficiency with thrombocytopenia and eczema is identified by the triad of thrombocytopenia, eczema, and susceptibility to infections, along with low IgM, elevated IgE and IgA, and varying degrees of cellular immune dysfunction.
• Cellular immunodeficiency with abnormal immunoglobulin synthesis is diagnosed based on infection symptoms, reduced or absent T-cell function, and varying degrees of antibody deficiency.

How is primary combined immunodeficiency treated?

• Symptomatic and supportive therapies include blood or platelet transfusions, splenectomy, and infection prevention.
• For SCID, irradiated inactivated immunocompetent cells may be transfused.
• Bone marrow transplantation for immune reconstitution, or fetal liver/thymus transplantation.
• Enzyme replacement therapy, physical therapy, etc.
• Gene therapy to correct genetic defects in immature immune cells.

Is primary combined immunodeficiency serious?

The prognosis is generally poor. Without effective treatments like bone marrow transplantation, most patients die before the age of 2. Rare cases of cellular immunodeficiency with abnormal immunoglobulin synthesis may survive until 18 years of age.

How can primary combined immunodeficiency be prevented?

• Screen for immunodeficiency disorders and assess whether the mother took teratogenic drugs during pregnancy.
• Minimize interpersonal contact to reduce infection risks.
• Infusion of nonspecific immune factors or immunoglobulins.
• Hematopoietic stem cell or bone marrow transplantation, fetal thymus transplantation to improve immune function.
• Gene therapy.