Assessment of the humoral immune system in adults with respiratory tract disease

Recurrent respiratory tract infections are a common problem, and can have various causes, including an underlying immunodeficiency. This thesis investigates the value of humoral immune status assessment in patients with respiratory tract infections, lung transplant candidates/recipients and the long-term treatment results of primary antibody deficiency with antibody replacement therapy.

For the most part, interpretation of the results from humoral immune status assessment is clear. However, some parts of the immune status screening protocol, such as mannose-binding lectin (MBL) deficiency, are less easily interpretable. As shown in Chapter 2, MBL-deficiency does not seem to be a contributing factor in patients presenting with recurrent respiratory tract infections. Therefore, the value of including MBL in the clinical immune status protocol can be questioned.

Another part of the immune status screening protocol is assessment of the response to pneumococcal polysaccharide vaccination. Usually only the antibody response of the IgG isotype is measured. In Chapter 3 and Chapter 4, it is shown that the antibody response to vaccination can also be impaired in other isotypes, and also in IgG subclasses. Impaired IgA and IgG2 antibody responses seem to be of clinical relevance, as they were associated with sinusitis (IgA), pneumonia (IgG2) and severity of bronchiectasis (IgA and IgG2).

Lung transplant candidates and recipients are a special population. After transplantation, all patients receive strong immunosuppressive therapy in order to prevent rejection. As shown in Chapter 5 a majority of lung transplant candidates had one or more abnormalities in the immune status investigation. Further, in Chapter 6 it is shown that humoral immune status significantly declines after lung transplantation. This was most outspoken in the first-year post-transplantation. Therefore, it can be recommended that revaccination with pneumococcal vaccines should be considered one year post-transplantation. Secondly, periodic monitoring of immunoglobulins, IgG subclasses and anti-pneumococcal antibodies should be included in routine clinical care.

Chapter 7 reviews the current literature on etiology, diagnosis, and treatment of primary antibody deficiency (PAD) and iatrogenic hypogammaglobulinemia (IHG). In PAD there is compelling evidence for the use of antibody replacement therapy (ART), mainly for more severe forms of PAD. For milder forms of PAD the evidence is more limited. Based on limited evidence, ART seems to be effective in reducing the infection frequency in IHG patients.

The study described in chapter 8 provides new data on the efficacy of antibody replacement therapy in patients with mild or severe humoral immunodeficiency. The results confirm the effectiveness of ART in mild humoral immunodeficiency and add to previously published literature that ART is also an effective therapy in patients with severe humoral immunodeficiency.

As shown in this thesis an antibody deficiency (also a mild antibody deficiency) can be the cause of recurrent respiratory tract infections. Systematic investigation of the humoral immune status can lead to this diagnosis. Treatment with antibody replacement therapy can significantly decrease the burden of this disease and prevent future organ damage. A high index of suspicion is necessary for diagnosing an antibody deficiency in patients with recurrent respiratory tract infections.