Specific antibody deficiency: pearls and pitfalls for diagnosis

Objective: To summarize the pitfalls associated with defining exactly what constitutes an "impaired" antibody response to polysaccharide antigens and the importance of documenting actual pyogenic infections before making a diagnosis of an immune deficiency. Specific antibody deficiency is an immune deficiency defined by the presence of normal quantitative levels of immunoglobulins, but impaired antibody responses to polysaccharide antigens, in patients presenting with frequent otosinopulmonary infections with pyogenic bacteria.

Data sources: PubMed review using the following keywords: specific antibody deficiency, pneumococcal vaccination, Salmonella vaccination, infectious sinusitis.

Study selection: This review focused on key studies that have been utilized to define what constitutes a "normal" humoral immune response to pneumococcal and Salmonella vaccination in healthy subjects and on published studies defining current expert opinion.

Results: Published studies demonstrate wide variability in response to pneumococcal vaccination in healthy individuals, making it daunting to define what constitutes an abnormal response. These challenges are exacerbated by striking laboratory variability in reporting results.

Conclusion: Clinical examinations in individuals with self-reported recurrent acute sinusitis or lower respiratory infections need to document an infectious etiology with pyogenic bacteria and must rule out an underlying primary airway inflammatory disorder before consideration is made regarding the presence of an immune deficiency. In addition, decision making regarding diagnosis and treatment of patients who are examined for humoral immunodeficiency should not hinge solely on the strict application of defined cutoffs for "normal" response to a single polysaccharide vaccine, but rather a global assessment of humoral immune function in the context of the clinical presentation.