Selective Polysaccharide Antibody Deficiency

Selective polysaccharide antibody deficiency is a condition where the immune system fails to produce protective antibodies against certain bacteria, even though overall antibody levels remain normal. This leaves affected individuals vulnerable to repeated respiratory infections caused by bacteria with sugar-coated surfaces.

Table of contents

• Disease Identification and Classification
• What Is Selective Polysaccharide Antibody Deficiency?
• Who Is Affected?
• Symptoms and Clinical Features
• What Causes This Condition?
• How Is It Diagnosed?
• Treatment and Management
• Outlook for Patients

Disease Identification and Classification

Specific polysaccharide antibody deficiency, SPAD, Specific anti-polysaccharide antibody deficiency, Selective anti-polysaccharide antibody deficiency, Specific antibody deficiency, Partial antibody deficiency, Impaired polysaccharide responsiveness

D80.8
4A01.02
C0398712

Selective polysaccharide antibody deficiency is recognized by the International Union of Immunology Societies as a primary immunodeficiency of unknown genetic cause^[5].

What Is Selective Polysaccharide Antibody Deficiency?

Selective polysaccharide antibody deficiency is a type of primary immunodeficiency (a disorder present from birth that affects the immune system) where people have normal levels of antibodies (proteins that help fight infections) in their blood, but cannot produce the specific antibodies needed to protect against certain bacteria^[1].

Among the five classes of antibodies, IgG plays the biggest role in protecting against infection. Some people have normal levels of all antibodies, including all subclasses of IgG, but they do not produce sufficient specific IgG antibodies to protect them from some viruses and bacteria that cause respiratory infections^[1].

The key problem in this condition is the inability to make antibodies against the polysaccharide (sugar) coat that covers certain bacteria. These bacteria include Streptococcus pneumoniae (pneumococci), Haemophilus influenzae, Moraxella catarrhalis, meningococci, and group B streptococci^[3][7].

Each individual IgG molecule is uniquely designed to protect against a specific germ. These molecules are called specific antibodies, and they are usually formed in response to natural exposure to bacteria and viruses, or through exposure to vaccines^[1].

Who Is Affected?

Although the exact prevalence is not really known, more than 100 cases have been reported in the scientific literature. The frequency ranges from 11 to 60 percent in selected patients with unexplained bacterial infections^[3].

The prevalence of this syndrome in children with recurrent respiratory infections is highly variable, with figures depending on the source of information reviewed, with a percentage of 5 to 15 percent being common in the general population^[5].

This condition can affect children older than 2 years or adults, although most of the published cases are adults^[3]. The condition can affect both sexes and people of all ages^[6].

Children less than 2 years of age often do not have a robust response to bacterial infections such as pneumococci and Haemophilus influenzae. This is primarily due to an inability to make antibodies against the polysaccharide coat that covers these bacteria. Most children begin to naturally make stronger immune responses to these bacteria around 2 years of age, and they can then fight off these infections more effectively^[1].

Higher prevalence in certain ethnic populations and familial cases suggest genetic factors are involved. The condition is likely heterogeneous with multiple causes^[3].

Symptoms and Clinical Features

People with selective polysaccharide antibody deficiency have frequent sinus and lung infections^[4]. Patients suffer from recurrent bacterial infections, mostly of the respiratory tract, such as lung infections (with or without bronchiectasis, a condition where the airways become permanently widened), recurrent bacterial sinus infections, or chronic inflammation of the sinuses and nasal passages^[3].

The symptoms of this condition include an increased occurrence of upper and lower respiratory infections^[6]. Less frequently, patients may develop sepsis (a life-threatening response to infection) and meningitis (infection of the membranes covering the brain and spinal cord)^[3].

Allergic manifestations are observed in about half of the patients^[3]. People may also have symptoms of allergies, such as a chronic runny and stuffy nose (rhinitis), a rash, and asthma. The severity of the disorder varies^[4].

Some individuals with low specific antibody levels may rarely get sick if other components of their immune system work well. T cells, complement proteins, IgM and IgA antibodies work together during a complete immune response, and if these other components function properly, they may compensate for the antibody deficiency^[1].

What Causes This Condition?

This immunodeficiency is likely heterogeneous with multiple causes. Higher prevalence in certain ethnic populations and familial cases suggest genetic factors are involved^[3].

Several hypotheses have been proposed concerning the cause of the disease, but the most likely is a defect in splenic marginal zone B cells (specialized immune cells in the spleen). This is supported by the observed impaired polysaccharide antibody response in patients who have had their spleen removed^[3].

Patients diagnosed with this type of immunodeficiency present alterations in the development and maturation of B cells and their formation of germinal centers (areas where B cells multiply and mature). Although the possible causes are quite clear, secondary causes that can cause an immunosuppressive effect, including the use of certain drugs, must be ruled out^[5].

How Is It Diagnosed?

Children are not tested for this disorder until after age 2 years because young healthy children may have frequent sinus and lung infections and weak responses to certain vaccines. Most children less than 2 years old have a normal developmental limitation in response to polysaccharide antigens, so the diagnosis cannot be made before this age^[3][4].

The diagnosis is established by identifying deficient antibody response to polysaccharide antigens (usually using the unconjugated Streptococcus pneumoniae vaccine, also called pneumococcal polysaccharide vaccine) contrasting with normal antibody levels (including the IgG subclasses) and unaffected antibody production to protein antigens such as tetanus toxoid and diphtheria^[3].

Testing consists of blood tests to measure levels of antibodies and to evaluate how well the body produces antibodies in response to vaccines. Normal levels of antibodies and an inadequate response to certain vaccines confirms the diagnosis^[4].

The response to pneumococcal capsular polysaccharide is tested using specialized laboratory tests. The results must be interpreted according to the guidelines issued in 2012 by the American Academy of Allergy, Asthma and Immunology (AAAAI) Working Group^[3].

A single bacterial type is considered to have normal response if the post-vaccination antibody level is greater than 1.3 micrograms per milliliter (considered to be protective) and/or achieves a 4-fold increase relative to the pre-vaccination value. A 2-fold increase is considered acceptable if the initial level was already greater than 1.3 micrograms per milliliter^[3].

A good vaccination response is defined if a normal response is observed for at least 50 percent (for children) to 70 percent (for adults) of the evaluated bacterial types^[3].

The diagnosis must not only be based on results of laboratory studies but must also be related to the clinical manifestations. Patients may have a diagnosis delay of years despite the frequency of infections and also have a risk of having structural complications due to the same infections^[5].

Treatment and Management

Treatment includes vaccination with the pneumococcal conjugate vaccine as part of routine childhood vaccinations. Children who have selective polysaccharide antibody deficiency respond to this vaccine, which differs from the pneumococcal polysaccharide vaccine^[4]. In conjugate vaccines, a protein is added to provoke a stronger immune response^[1].

Sinus and lung infections and allergy symptoms are treated promptly with appropriate medications^[4]. The treatment of this condition is based on preventing recurrent infections by known microorganisms^[5].

Occasionally, when infections continue to recur after treatment, people are given antibiotics (such as amoxicillin and trimethoprim/sulfamethoxazole) to prevent the infections from recurring^[4].

Rarely, when infections recur frequently despite use of these preventive antibiotics, people are given injections of immune globulin (antibodies obtained from the blood of people with a normal immune system). In the case of serious infections, the use of intravenous or subcutaneous immunoglobulin may be necessary^[4][5]. Immune globulin may be injected into a vein (intravenously) or under the skin (subcutaneously)^[4].

Very rarely, the use of immunoglobulin replacement therapy may be needed^[6].

Outlook for Patients

With appropriate treatment, the outlook for people with selective polysaccharide antibody deficiency is generally good and most people live normal, healthy lives^[6].

Some children have a form of the disorder that resolves on its own over time^[4].