Reply to Spellberg.

Department of Medicine, Division of Infectious Diseases and.
Clinical Infectious Diseases (Impact Factor: 8.89). 10/2011; DOI: 10.1093/cid/cir718
Source: PubMed
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    ABSTRACT: To characterize more fully the immunologic basis for increased susceptibility to infection in patients with low serum concentrations of IgG2, we identified eight infection-prone children, 1 to 2 years of age, with serum IgG2 concentrations greater than 2 SD below the mean for age and followed their serologic and clinical courses for 1 to 3 years. Two of the eight children became clinically and immunologically normal and may have had transient IgG2 deficiency with an exaggerated developmental delay of this late-maturing subclass. The remaining six subjects had persistently subnormal or low-normal serum IgG2 levels and continued to experience frequent infections. All six of these children responded poorly to Haemophilus influenzae type b (Hib) polysaccharide, and four of six responded poorly to Streptococcus pneumoniae type 3 polysaccharide. Both IgG1 and IgG2-specific antibody responses to these vaccines were abnormal. Three of these six children also responded poorly to tetanus toxoid, an antigen that normally induces a predominant IgG1 response. Although five of these six children produced antibodies in response to Hib polysaccharide protein conjugate vaccine, three of four given Hib oligosaccharide CRM conjugate vaccine required booster doses to respond, a pattern of response characteristic of infants less than 6 months of age. Further, although serum concentrations of IgG1 were normal, peripheral blood mononuclear cells from four of six children tested produced extremely small amounts of IgG1 and IgG3 as well as IgG2. Finally, varied patterns of abnormalities of IgG, IgA, IgM, and IgG4 became apparent in five of the six children with persistently low serum IgG2 values. This study demonstrates that subnormal serum concentrations of IgG2 may be associated with varied patterns of immunologic dysfunction, some of which are evolving and may be responsible for increased susceptibility of these children to infection.
    Journal of Pediatrics 05/1990; 116(4):529-38. DOI:10.1016/S0022-3476(05)81598-7 · 3.79 Impact Factor
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    ABSTRACT: The aim of this study was to investigate measles-specific immunoglobulin G (IgG) subclass profile in vaccinated children and in adults with natural infection. Serum samples were collected before and 30 days after vaccination. The sera from 51 late convalescent adults and seven adults with natural measles infection at the 12th day after onset of rash have been also investigated. Measles IgG antibodies and specific IgG subclasses were tested by enzyme-linked immunosorbent techniques. In children younger than 3 years, the predominant subclass was IgG3, which contributed, on average, 63.3% of the total IgG response. The contributions of specific IgG1 and IgG4 to the total IgG antimeasles response were lower (19.9% and 16.8%, respectively), whereas IgG2 was not found. In contrast, in the group of children older than 4 years, just IgG2 was a predominant subclass; it contributed 42.6% of the total IgG response. Other subclasses were also present but the contribution was much lower. In adult volunteers with measles history, IgG2 was a predominant subclass of total IgG. Thus, in early convalescence IgG2 contributed 62% of the total IgG response, whereas in late convalescence the contribution was lower (41.4%). There were no visible differences in IgG subclass composition between subjects with natural infection and vaccinated children except those below 3 years of age. The humoral immune response of such subjects is immature and the IgG2 subclass of virus-specific antibodies has not been revealed in the sera.
    Clinical and Diagnostic Laboratory Immunology 08/2005; 12(7):845-7. DOI:10.1128/CDLI.12.7.845-847.2005 · 2.51 Impact Factor
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    ABSTRACT: Mouse IgG3 subclass antibodies predominate in humoral responses to bacterial polysaccharide antigens. The reasons for this isotype restriction are not fully understood. Here, Neil Greenspan and Laurence Cooper propose that intermolecular cooperativity, a novel mechanism of antibody binding, may help to explain the preferential expression of IgG3 antibodies in these responses.
    Immunology Today 06/1992; 13(5):164-8. DOI:10.1016/0167-5699(92)90120-V · 9.49 Impact Factor


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