title: Immunological factors and risk of infection in plateau phase myeloma.
abstract: OBJECTIVE
  A series of patients with myeloma were investigated to assess whether immunological risk factors predisposing to serious infection could be identified.
  
  
  METHODS
  Patients (n = 102) with predominantly plateau phase myeloma were monitored prospectively for infections. Immunological parameters including total non-paraprotein immunoglobulins and specific antibody titres were measured in all patients and compared with a control population of healthy individuals of a similar age; response to immunisation with Pneumovax II, tetanus and diphtheria toxoids and IgG subclasses were measured in a subgroup of 41 patients. Other characteristics investigated for any association with infection included age, sex, paraprotein type, disease stage, and chemotherapy.
  
  
  RESULTS
  Specific antibody titres to pneumococcal capsular polysaccharides and tetanus and diphtheria toxoids were significantly reduced compared with the control population. Low antipneumococcal and anti Escherichia coli titres correlated with risk of serious infection and low anti-pneumococcal titres with severity of non-paraprotein immunosuppression. In 41 immunised patients responses to Pneumovax II, tetanus and diphtheria toxoids were poor; IgG subclass levels were significantly reduced and a poor IgG response to Pneumovax II immunisation was associated with an increased risk of septicaemia and low IgG2 levels. The overall serious infection rate was 0.92 infections per patient year and was four times higher during periods of active disease (1.90) compared with plateau phase myeloma (0.49). The predominant site of infection was the respiratory tract. Clinical and laboratory parameters showed only male sex and reduced non-paraprotein IgG and IgA levels to be significantly associated with at least one serious infection.
  
  
  CONCLUSIONS
  A subgroup of patients with myeloma with poor IgG responses to exogenous antigens, who are at increased risk of serious infection, can be identified and may benefit from replacement immunoglobulin therapy to reduce the risk of infection.
authors.affiliation: Department of Immunology, John Radcliffe Hospital, Oxford.
authors.forename: R M
authors.initials: RM
authors.lastname: Hargreaves
authors.forename: J R
authors.initials: JR
authors.lastname: Lea
authors.forename: H
authors.initials: H
authors.lastname: Griffiths
authors.forename: J A
authors.initials: JA
authors.lastname: Faux
authors.forename: J M
authors.initials: JM
authors.lastname: Holt
authors.forename: C
authors.initials: C
authors.lastname: Reid
authors.forename: C
authors.initials: C
authors.lastname: Bunch
authors.forename: M
authors.initials: M
authors.lastname: Lee
authors.forename: H M
authors.initials: HM
authors.lastname: Chapel
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000907:Antibodies, Bacterial / Q000097:blood; D005260:Female; D006801:Humans; D007114:Immunization; D016867:Immunocompromised Host; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000097:blood; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications / Q000188:drug therapy / Q000276:immunology*; D009894:Opportunistic Infections / Q000150:complications / Q000276:immunology*; D011446:Prospective Studies; D012307:Risk Factors; D013997:Time Factors
chemical_list: D000907:Antibodies, Bacterial; D007074:Immunoglobulin G