Clinical and Laboratory Characteristics of 75 Patients With Specific Polysaccharide Antibody Deficiency Syndrome

Abstract

Cheng YK, Decker PA, O’Byrne MM, Weiler CR. Ann Allergy Asthma Immunol. 2006;97:306–311 PURPOSE OF THE STUDY. To study the clinical and laboratory characteristics of patients with specific polysaccharide antibody deficiency syndrome. STUDY POPULATION. This was a retrospective review of records obtained over 8 years of patients from the Mayo Clinic (Rochester, MN) who were found to have recurrent infection defined as ≥4 infections per year and an immunoglobulin G (IgG) level of >500 mg/mL. METHODS. Serious infections were defined as pneumococcal sepsis, meningitis, pneumonia, or deep-seated abscess. Specific polysaccharide antibody deficiency syndrome (SPADS) is empirically defined as <9 of 12 serotype responses to vaccination with Pneumovax (titers checked preimmunization and 2–4 weeks postimmunization ×2), and no other documented, established primary or secondary immunodeficiency syndrome. An adequate response to pneumococcal serotypes contained in the vaccine was defined as reaching the protective level defined by the laboratory assay. Loss of immune response 6 months after vaccination was also assessed in patients with recurrent infection. In such patients, vaccination was repeated and serologies were remeasured. RESULTS. Seventy-five patients met the inclusion criteria. The median age at presentation was 42 years (range: 0–76 years), and the median age at diagnosis was 48 years (range: 4–81 years). The median interval between onset of symptoms and diagnosis of SPADS was 4 years. Sixty-nine percent of the patients were female, and 83% were white. The most common documented infections (in order of occurrence) were sinus infection, pneumonia, bronchitis, and ear infections; only 7% of the patients had documented sepsis, meningitis, or deep-tissue abscesses. Eight percent had autoimmune disorder or rheumatic disease. Sixteen percent of the patients had 0 of 12 responses to Pneumovax; 72% had 1 to 6 of 12 responses; and 12% had 7 to 8 of 12 responses. Patients under 18 years of age tended to have less response. The median IgG2 level (150 mg/dL) for patients with 0 responses to Pneumovax tended to be lower compared with patients with >1 response (193 mg/dL; P = .06). When measured, the majority (31 of 35) of the patients had protective levels of antibody to tetanus and diphtheria (18 of 19). In vitro lymphocyte-stimulation test results were normal in the vast majority of patients when measured. Thirty patients were treated with a standard intravenous Ig (IVIg) therapy, 400 mg/kg per month for an undetermined time period. Patients with a higher number of infections (P = .003) and fewer responses to Pneumovax (P = .01) were more likely to receive IVIg. Of the patients receiving IVIg, the number of infections after treatment was significantly lower (median: 1 vs 8; P < .001). CONCLUSIONS. SPADS is a disorder of humoral immunity that is seen in patients with recurrent infections. Response to unconjugated pneumococcal vaccine is abnormal despite normal total IgG levels. Other immune abnormalities are not typically seen. Patients with more frequent infections have less responses to Pneumovax and may clinically respond to IVIg therapy. REVIEWER COMMENTS. This study was chosen for review because of the potential frequency of this problem in patients with recurrent infection. This descriptive, retrospective study had a very mixed population, and some of the patients included would not meet a rigorous definition of SPADS (some with autoimmune disease, poor response to protein antigens). The definition of an abnormal response to pneumococcal vaccination was not well established. The practice parameter for the diagnosis and management of primary immunodeficiency defines response to pneumococcal polysaccharide vaccine as postimmunization antibody concentration of >1.3 μg/mL or fourfold rise over baseline. Children younger than 2 years should not be given a diagnosis of SPADS, because they have a physiologic impairment of antibody production to unconjugated polysaccharide antigens. Prospective studies for a more specific definition and response to treatment are needed for patients with specific antibody deficiency and normal IgG levels.