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Immunoglobulin Allotypes and Immune Response to Meningococcal Group B Polysaccharide

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Immunoglobulin Allotypes and Immune Response to Meningococcal Group B Polysaccharide Immunoglobulin allotypes and immune response to meningococcal group B polysaccharide. J P Pandey, … , H H Fudenberg, C B Loadholt J Clin Invest. 1981;68(5):1378-1380. https://doi.org/10.1172/JCI110387. Research Article Serum samples were collected from 120 healthy adult volunteers (105 Caucasians and 15 Negros) before and after immunization with meningococcal polysaccharide (MPS) group B vaccine. Antibodies to MPS group B were measured and sera were typed for several Gm and Km(1) allotypes. A significant association was found between the Km(1) allotype and immune response to MPS group B in Caucasians. Find the latest version: https://jci.me/110387/pdf Immunoglobulin Allotypes and Immune Response to Meningococcal Group B Polysaccharide JANARDAN P. PANDEY, WENDELL D. ZOLLINGER, H. HUGH FUDENBERG, and C. BOYD LOADHOLT, Department of Basic and Clinical Immunology and Microbiology, Department of Biometry, Medical University of South Carolina, Charleston, South Carolina 29425; Department of Bacterial Diseases, Walter Reed Army Institute of Research, Washington, D. C. 20012 A B S T R A C T Serum samples were collected from METHODS 120 healthy adult volunteers (105 Caucasians and 15 Subjects and vaccines. A total of 120 healthy adult male Negros) before and after immunization with meningo- volunteers (105 Caucasians and 15 Negroes), 18-21 yr of age, coccal polysaccharide (MPS) group B vaccine. Anti- were vaccinated with meningococcal group B vaccine (120 bodies to MPS group B were measured and sera were ,ig in 0.5 ml of saline), either lot BP2-WZ-2 or lot BP2-4. Gm A The two lots of vaccine are of similar composition and anti- typed for several and Km(l) allotypes. significant genicity as determined by in vitro tests. Both are approxi- association was found between the Km(l) allotype and mately a 1:1 noncovalent complex of group B polysaccharide immune response to MPS group B in Caucasians. and outer membrane protein. Blood was collected immediately before and 2 wk after immunization. INTRODUCTION Antibody determination. Antibodies to MPS group B were determined by a radioactive antigen binding assay. This Major histocompatability complex (MHC)-linked and assay uses group B polysaccharide intrinsically labeled with tritium at a sp act of -200-500 cpm/ng. Chlorine-36 as immunoglobulin (Ig) allotype-linked immune response Cl- was added as a volume maker. After incubation of (Ir) genes have been extensively studied in experi- antigen and antiserum at 4'C overnight, an equal volume mental animals (1). Several recent observations by us of cold saturated ammonium sulfate was added and the and others suggest that such genes also exist in man sample was centrifuged to pellet the precipitate. A sample existence of the supernatant was counted and calculations were made (2-4). The data presented here indicate the as described by Gotschlich et al. (7). As a standard, a rela- of an allotype-linked Ir gene(s) that regulates the tively high titered human serum (58 ug antibody per milliliter humoral immune response to meningococcal poly- as determined by quantitative precipitin assay) was arbi- saccharide (MPS) group B. trarily assigned a value of 100 U of antibody per milli- B liter. Group Neisseria meningitidis continues to be Ig allotyping. Our standard hemagglutination inhibition responsible for a major proportion of meningococcal technique (8) was used to detect Gm and Km(l) markers, the disease in the United States, Europe and England hereditary antigenic determinants on the constant regions ofy (5). Protection from meningococcal disease has been chains and K-type light chains, respectively. Serum samples correlated with the presence of serum bactericidal were typed for Gm antigens 1, 2, 3, 5, 6, 13, 14, 17 and 21, as well as Km(l). antibodies (6). Individuals who are "nonresponders" Statistical analysis. Correlation coefficients were cal- may thus be at an increased risk of developing group culated to determine whether there was an association be- B meningococcal disease. Our findings suggest geneti- tween preimmunization antibody levels and the postim- cally determined differences in the magnitude of munization increase in antibody titer, and analysis of variance was used to determine whether there was any humoral immune responses to this organism, which association between Gm or Km(l) phenotypes and the im- might influence disease susceptibility. mune response to MPS group B. All computations were performed using University of California at Los Angeles Publication no. 465 from the Department of Basic and computer program BMDP2V: Analysis of Variance and Co- Clinical Immunology and Microbiology, Medical University variance. of South Carolina. Research supported in part by U. S. Public Health Service grants HD-09938 and CA-25746. Received for publication 22 June 1981 and in revised form RESULTS 25 August 1981. 2Abbreviations used in this paper: Ir, immune response; In contrast to MPS groups A and C, for which a signifi- MHC, major histocompatibility complex; MPS, meningococcal cant negative correlation has been reported between polysaccharide. preimmunization titer and titer increase (9), we found 1378 J. Clin. Invest. © The American Society for Clinical Investigation, Inc. * 0021-9738/81/11/1378/03 $1.00 Volume 68 November1981 1378 -1380 TABLE I taken with respect to Km allotypes. Km, like Gm, Mean Immune Response to Meningococcal Group B may also influence Ig concentrations and antibody Polysaccharide in Relation to Gm and Km(l) activity because it is present in all Ig classes, not merely Phenotypes in Caucasians IgG. A second explanation may be that there exist in Phenotype No. Mean response* man Ir genes that regulate the immune responses to MPS groups B and C, and that alleles of these genes Gm 1, 17; 21 4 19.25±9.18 are in linkage disequilibrium with the Km alleles. Al- Gm 1, 2, 17; 21 10 2.70±2.45 though conclusive evidence for the existence of Ir Gm 3; 5, 13, 14 48 13.44±1.48 genes can be obtained only after family studies Gm 1, 3, 17; 5, 13, 14, 21 32 11.53±3.21 (which Gm 1, 2, 3, 17; 5, 13, 14, 21 11 11.18±4.53 are difficult to undertake in humans), the data presented Km(l)+ 18 18.22±3.52t here are suggestive of such genes in man. Km(l)- 87 10.49±1.44 Bactericidal antibodies induced by MPS group C are predominantly IgG (11), and Siber et al. (12) * Mean immune response is difference between postim- have recently reported a correlation between serum munization and preimmunization antibody levels in units of IgG2 concentrations and the antibody response to anti-MPS B per milliliter of serum. several other bacterial polysaccharide antigens. In t F = 4.77; P = 0.031. contrast, the antibodies induced by MPS group B are IgM (5). Involvement of Km(l) in immune responses no significant correlation between preimmunization to both MPS groups B and C can be explained by asso- antibody levels and immune response to MPS group B. ciation of the K chain with both 'y and ,u chains. The mean immune responses to MPS group B in One way to corroborate the results reported here Caucasian recipients with various Gm and Km(l) would be to study individuals who were immunized phenotypes are shown in Table I. No significant as- with MPS group B and nevertheless developed sociations were found between any of the Gm pheno- meningococcal meningitis. Our results would predict types and immune response to MPS group B; how- such people to be predominantly Km(l) negative. ever, a significant association was found between Such studies are currently in progress in our laboratory. Km(1) and immune response to MPS group B (F = 4.77, In future studies of the kind reported here, it would P = 0.031). The mean preimmunization levels of anti- be interesting to study the same group of individuals body to MPS group B for subjects positive for Km(l) for both Ig allotypes and HLA antigens. It has been and those without this allotype were approximately shown that HLA- and Ig allotype-linked genes inter- the same (7.67 vs. 7.56 U/ml of serum). After im- act in determining levels of serum antibodies to the munization, however, the immune response was bacterial antigen monomeric flagellin (3), and a similar dramatically higher in Km(l) positive than in Km(l) situation may exist for other immunogens. Such inter- negative individuals (18.22 vs. 10.49 U/ml of serum). actions between polymorphic genes may provide not The significance of the association between Km(l) and only a mechanism for increasing the specificity of anti- immune response to MPS group B in Negros (Table body reactions but also a more flexible means of II) was borderline (P = 0.077); however, because evolutionary adaptation to newly encountered and of the small number of Negro subjects in the study, potentially harmful infections (3). Further studies of no definite conclusions can be drawn with regard to immunogenetic markers and antibody responses may this group. also shed some light on the selective mechanism that maintains HLA, Gm, and Km polymorphisms; indeed, associations between these antigenic determinants and DISCUSSION specific antibody responses may be the selective force The significant association between Km(l) and immune response to MPS group B in Caucasians is noteworthy. TABLE II In an earlier study (2), we reported a significant asso- Mean Immune Response to Meningococcal Group B Polysaccharide in Relation to Gm and ciation between Km(l) and the response to MPS group Km(l) Phenotypes in Negroes C in Caucasian infants 18-20 mo old. Two probable explanations can be forwarded to account for these Phenotype No. Mean response results. First, the Km(l) allotype itself may regulate Gm 1, 17; 5, 13, 14 8 17.12±6.38 the immune responses to MPS group B and C.
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