title: Hypogammaglobulinemia in children after allogeneic hematopoietic stem cell transplantation: a cytokine mediated immunoglobulin isotype class switch arrest?
abstract: BACKGROUND
  Hypogammaglobulinemia (hypo-IgG) is common early post-HSCT in children, occasionally necessitating long-term immunoglobulin (Ig) G replacement therapy. IgG replacement may not reduce mortality, although infectious complications are decreased
  
  
  METHODS
  Clinical data and samples from 86 children were analyzed retrospectively with the aim to identify risk factors for developing long-term hypo-IgG (i.e., requiring ≥ 3 months IgG replacement) post-HSCT and studying the underlying biology. Laboratory studies covered serum cytokines, IGHG2 genotyping and routine laboratory investigations. Results were analyzed statistically.
  
  
  RESULTS
  Forty-eight percent of the children developed long-term hypo-IgG. These children were younger (<5 years) and had higher acute GvHD incidence, but had better overall survival (88% vs. 69%, P = 0.036). Significantly lower Ig levels post-HSCT but equal immune cell recovery were seen in patients with long-term hypo-IgG compared with those of transient or no hypo-IgG. Pre-HSCT IL-6 and -7 and post-HSCT BAFF and APRIL levels were significantly higher in the long-term hypo-IgG group.
  
  
  CONCLUSIONS
  Findings suggests an unfavorable cytokine milieu for graft-derived immune recovery, possibly inducing Ig isotype class switch arrest. Younger age, acute GvHD, and higher pre-HSCT IL-6 levels were identified as significant risk factors for long-term hypo-IgG. Long-term hypo-IgG post-HSCT does not need to be unfavorable and could be an effect of deteriorated cytokine signaling.
authors.affiliation: Division of Pediatrics, Department of Clinical Science, Intervention and Technology (CLINTEC); and; Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Sundin
authors.forename: Mats
authors.initials: M
authors.lastname: Remberger
authors.forename: Henric
authors.initials: H
authors.lastname: Lindqvist
authors.forename: Brigitta
authors.initials: B
authors.lastname: Omazic
authors.forename: Berit
authors.initials: B
authors.lastname: Sundberg
authors.forename: Mehmet
authors.initials: M
authors.lastname: Uzunel
authors.forename: Jacek
authors.initials: J
authors.lastname: Winiarski
mesh_terms: D000293:Adolescent; D000328:Adult; D000361:Agammaglobulinemia / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000494:pharmacology*; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality; D019337:Hematologic Neoplasms / Q000150:complications / Q000401:mortality / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000187:drug effects*; D007132:Immunoglobulin Isotypes / Q000187:drug effects*; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D012189:Retrospective Studies; D015996:Survival Rate; D055815:Young Adult
chemical_list: D016207:Cytokines; D007132:Immunoglobulin Isotypes
keywords: IgG; immunoglobulin; pediatric; subcutaneous; substitution