Journal of Clinical Immunology

, Volume 31, Issue 3, pp 315–322 | Cite as

Effectiveness of Immunoglobulin Replacement Therapy on Clinical Outcome in Patients with Primary Antibody Deficiencies: Results from a Multicenter Prospective Cohort Study

  • Isabella Quinti
  • Annarosa Soresina
  • Andrea Guerra
  • Roberto Rondelli
  • Giuseppe Spadaro
  • Carlo Agostini
  • Cinzia Milito
  • Amelia Chiara Trombetta
  • Marcella Visentini
  • Helene Martini
  • Alessandro Plebani
  • Massimo Fiorilli
  • IPINet Investigators
Article

Abstract

A 5-years multicenter prospective study on 201 patients with common variable immunodeficiencies and 101 patients with X-linked agammaglobulinemia over a cumulative follow-up period of 1,365 patient-years was conducted to identify prognostic markers and risk factors for associated clinical co-morbidities, the effects of long-term immunoglobulin treatment and the IgG trough level to be maintained over time required to minimise infection risk. Overall, 21% of the patients with common variable immunodeficiencies and 24% of patients with X-linked agammaglobulinemia remained infection free during the study. A reduction of pneumonia episodes has been observed after initiation of Ig replacement. During the observation time, pneumonia incidence remained low and constant over time. Patients with pneumonia did not have significant lower IgG trough levels than patients without pneumonia, with the exception of patients whose IgG trough levels were persistently <400 mg/dL. In X-linked agammaglobulinemia, the only co-morbidity risk factor identified for pneumonia by the final multivariable model was the presence of bronchiectasis. In common variable immunodeficiencies, our data allowed us to identify a clinical phenotype characterised by a high pneumonia risk: patients with low IgG and IgA levels at diagnosis; patients who had IgA level <7 mg/dL and who had bronchiectasis. The effect of therapy with immunoglobulins at replacement dosage for non-infectious co-morbidities (autoimmunity, lymphocytic hyperplasia and enteropathy) remains to be established. A unique general protective trough IgG level in antibody deficiency patients will remain undefined because of the major role played by the progression of lung disease in X-linked agammaglobulinemia and in a subset of patients with common variable immunodeficiencies.

Keywords

Immunoglobulin replacement common variable immunodeficiency X-linked agammaglobulinemia bronchiectasis IgA effectiveness 

Notes

Acknowledgments

We wish to thank all the patients who participated to this study as well as their families, and the Jeffrey Modell Foundation. This work was supported by grant of the European Commission, HEALTH-F2-2008-201549

Conflict of Interests

The authors declare no competing financial interests.

Supplementary material

10875_2011_9511_MOESM1_ESM.doc (32 kb)
Supplemental Table I List of data collected in the Italian database: full blood counts, chemistries, serum immunoglobulin levels were performed four times per year. Chest and sinus CT scans were performed every 4 years, gastrointestinal endoscopy with biopsy every 2 years or when indicated. Disease-associated clinical co-morbidities such as X-ray defined pneumonia, acute and chronic sinusitis, meningitis, sepsis, diarrhoea, bronchiectasis confirmed by CT, histologically defined chronic lymphatic hyperplasia, chronic diarrhoea, splenomegaly confirmed by ultrasound, autoimmunity were collected in a structured questionnaire filed by one physician per centre on a yearly basis. (DOC 31 kb)
10875_2011_9511_MOESM2_ESM.doc (731 kb)
Supplemental Table II Age at diagnosis, age at the end of the study, basal IgG, IgA, IgM;, IgA, IgM and IgG trough levels at the end of the study and delta IgG, in 201 patients with CVIDs Results are expressed as milligrams per deciliter. (DOC 731 kb)
10875_2011_9511_MOESM3_ESM.doc (219 kb)
Supplemental Table III Age at diagnosis, age at the end of the study, basal IgG, IgA, IgM;, IgA, IgM and IgG trough levels at the end of the study and delta IgG, in 101 patients with XLA. Results are expressed as mg/dL. (DOC 219 kb)
10875_2011_9511_Fig3_ESM.jpg (33 kb)

Supplemental Figure 1 Study design: 101 XLA patients and 201 CVIDs patients have been enrolled in a 5 years prospective study. Retrospective datasets were available from diagnosis. Mean age at diagnosis (±S.D.) and mean age at the last year of follow-up (FU) (±S.D.) are shown. (JPEG 32 kb)

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Isabella Quinti
    • 1
  • Annarosa Soresina
    • 2
  • Andrea Guerra
    • 1
  • Roberto Rondelli
    • 3
  • Giuseppe Spadaro
    • 4
  • Carlo Agostini
    • 5
  • Cinzia Milito
    • 1
  • Amelia Chiara Trombetta
    • 1
  • Marcella Visentini
    • 1
  • Helene Martini
    • 1
  • Alessandro Plebani
    • 2
  • Massimo Fiorilli
    • 1
  • IPINet Investigators
  1. 1.Department of Clinical ImmunologySapienza University of RomeRomeItaly
  2. 2.Department of PediatricsUniversity of BresciaBresciaItaly
  3. 3.Department of Onco-haematologyUniversity of BolognaBolognaItaly
  4. 4.Department of Clinical ImmunologyUniversity of NaplesNaplesItaly
  5. 5.Department of Clinical ImmunologyUniversity of PaduaPaduaItaly

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