Diagnosis, Characteristics, and Outcome of Selective Anti-polysaccharide Antibody Deficiencies In A Retrospective Cohort of 55 Adult Patients

Abstract

Selective anti-polysaccharide antibody deficiency (SPAD) predisposes to encapsulated bacterial infections. The diagnosis is challenging, and literature reports are scarce in adult patients, we therefore aim to describe the demographics, infectious complications, therapeutic strategies, and outcome of adult patients. We conducted a multicenter observational study involving 55 adult patients with SPAD. The median [interquartile range, IQR] age was 45 [36-60] years at diagnosis of SPAD, and 75% of patients were female. Twenty-one patients (38%) had a history of allergic and/or inflammatory disease, mainly asthma (n = 12), and rheumatic diseases (n = 6). Twelve patients (22%) were diagnosed after a single severe infection and 43 (78%) in a context of recurrent benign and/or severe infections. In the latter, the median time from first infections to diagnosis was 74.5 [33-167] months. Diagnostic delay was significantly higher in patients presenting with bronchiectasis than in those without (122 months [33-219.5] vs 24 months [14.5-74.5], p = 0.0042). In 22 patients (40%) receiving immunoglobulin replacement therapy (IgRT), the mean (min-max) frequency of antibiotic courses decreased from 7.9 (2-18) to 0.7 (0-2) courses per year (p < 0.001) with a median follow-up period of 46 [27-73] months. Patients diagnosed after a single severe infection did not have any relapse during a median follow-up of 85 [80.5-104.5] months after diagnosis. Adult patients with SPAD have allergic or inflammatory disorders which could contribute to the diagnostic delay. IgRT is effective in preventing recurrent infections. Further studies are warranted to confirm if SPAD should be considered after a first unexplained severe bacterial infection.

Keywords: Asthma; Encapsulated bacterial infections; Immunoglobulin replacement therapy; Preventive antibiotherapy; Primary immunodeficiency; Selective anti-polysaccharide antibody deficiency; Specific antibody deficiency.

Fig. 1

Infectious phenotypes of SPAD and patient management. a Distribution of SPAD phenotype among 3 patient groups: (i) a single severe infection, (ii) recurrent benign infections only and (iii) recurrent infections with at least 1 severe infection requiring hospitalization, with therapeutic management (b) Repartition of biologic phenotypes vaccine response impairment among the 3 infectious groups, defined as mild (green), moderate (orange) or severe (red) vaccine response impairment (according to [7]) * 2 missing data

Fig. 2

Diagnostic delay according to presence or absence of bronchiectasis

Fig. 3

Change in the number of antibiotic courses per year before and after introducing IgRT (n = 22)

Fig. 4

Infectious events in 6 patients with reduction or discontinuation of IgRT. ICU, intensive care unit; IgRT, immunoglobulin replacement therapy; IV, intravenous

Fig. 5

SPAD diagnosis and management according to the infectious complications. *Relevant bacterial infections are RTIs and/or invasive infection with encapsulated bacteria, when the patient’s history or investigations do not explain the frequency or the severity of the infections. **Complement explorations and search of Howell-Jolly bodies are indicated in invasive infection with encapsulated bacteria. *** SSA must be used if locally available, OVA can be used in other cases, but SSA will be mandatory in many cases (see Lopez et al. [11]). IgRT: immunoglobulin replacement therapy; IFE, immunofixation electrophoresis; OVA, overall anti-pneumococcal response assay; RTIs: respiratory tract infections; SPAD: specific antibody antibody deficiency; SPEP: serum protein electrophoresis; SSA: single-serotype assay