Mary T Bausch-Jurken1, James W Verbsky2, Katherine A Gonzaga1, Nancy P Elms1, Mary K Hintermeyer3, Stephen B Gauld4, John M Routes5. 1. Department of Pediatrics, Divisions of Allergy and Clinical Immunology, Medical College of Wisconsin, 9000 W. Wisconsin Ave, B440, Milwaukee, WI, 53226, USA. 2. Department of Pediatrics, Division of Rheumatology, Medical College of Wisconsin, Milwaukee, WI, USA. 3. Children's Hospital of Wisconsin, Milwaukee, WI, USA. 4. Immunology/Dermatology, AbbVie Inc, North Chicago, IL, USA. 5. Department of Pediatrics, Divisions of Allergy and Clinical Immunology, Medical College of Wisconsin, 9000 W. Wisconsin Ave, B440, Milwaukee, WI, 53226, USA. jroutes@mcw.edu.
Abstract
PURPOSE: The specific antibody response to the unconjugated 23-valent pneumococcal polysaccharide vaccine is one of the most common tests used to assess for possible humoral immunodeficiency. The results can be difficult to interpret because most people have been immunized with one or more of the pneumococcal vaccines and there is controversy regarding what constitutes a normal response. To circumvent this problem, we developed an ELISA to measure IgG-specific antibodies to the Salmonella Vi Typhim (S. Typhim) vaccine, a pure polysaccharide vaccine, which is a neoantigen for the vast majority of people in the USA. METHODS: We compared the pre- and post-vaccination serum titers to the Vi Typhim vaccine in healthy controls (n = 22), patients previously diagnosed with a primary immunodeficiency (n = 30), and patients referred for possible humoral immune deficiency (n = 29). We also determined if the S. Typhim vaccine could be used to assess specific antibody responses in people on antibody replacement therapy. RESULTS: Following immunization with the S. Typhim vaccine, we found that a 2-fold increase in titers is 100% sensitive and specific in detecting known humoral immune deficiencies as determined by ROC curve analysis. This cut-off value was successfully applied to possible immune deficiency patients (n = 29), resulting in the diagnosis of seven subjects with humoral immunodeficiency. The use of immunoglobulin replacement therapy did not affect the median response ratios compared to subjects not receiving gammaglobulin. CONCLUSION: This study suggests that measurement of the specific antibody response to the S. Typhim vaccine may have advantages over pneumococcal vaccination in the evaluation of the humoral immune response.
PURPOSE: The specific antibody response to the unconjugated 23-valent pneumococcalpolysaccharide vaccine is one of the most common tests used to assess for possible humoral immunodeficiency. The results can be difficult to interpret because most people have been immunized with one or more of the pneumococcal vaccines and there is controversy regarding what constitutes a normal response. To circumvent this problem, we developed an ELISA to measure IgG-specific antibodies to the Salmonella Vi Typhim (S. Typhim) vaccine, a pure polysaccharide vaccine, which is a neoantigen for the vast majority of people in the USA. METHODS: We compared the pre- and post-vaccination serum titers to the Vi Typhim vaccine in healthy controls (n = 22), patients previously diagnosed with a primary immunodeficiency (n = 30), and patients referred for possible humoral immune deficiency (n = 29). We also determined if the S. Typhim vaccine could be used to assess specific antibody responses in people on antibody replacement therapy. RESULTS: Following immunization with the S. Typhim vaccine, we found that a 2-fold increase in titers is 100% sensitive and specific in detecting known humoral immune deficiencies as determined by ROC curve analysis. This cut-off value was successfully applied to possible immune deficiencypatients (n = 29), resulting in the diagnosis of seven subjects with humoral immunodeficiency. The use of immunoglobulin replacement therapy did not affect the median response ratios compared to subjects not receiving gammaglobulin. CONCLUSION: This study suggests that measurement of the specific antibody response to the S. Typhim vaccine may have advantages over pneumococcal vaccination in the evaluation of the humoral immune response.
Authors: Francisco A Bonilla; Isil Barlan; Helen Chapel; Beatriz T Costa-Carvalho; Charlotte Cunningham-Rundles; M Teresa de la Morena; Francisco J Espinosa-Rosales; Lennart Hammarström; Shigeaki Nonoyama; Isabella Quinti; John M Routes; Mimi L K Tang; Klaus Warnatz Journal: J Allergy Clin Immunol Pract Date: 2015-11-07
Authors: S Sánchez-Ramón; J de Gracia; A M García-Alonso; J J Rodríguez Molina; J Melero; A de Andrés; J M García Ruiz de Morales; A Ferreira; J G Ocejo-Vinyals; J J Cid; J M García Martínez; T Lasheras; M L Vargas; J Gil-Herrera; M C García Rodríguez; J L Castañer; L I González Granado; L M Allende; P Soler-Palacin; L Herráiz; M López Hoyos; J M Bellón; G Silva; D M Gurbindo; J Carbone; C Rodríguez-Sáinz; N Matamoros; A R Parker; E Fernández-Cruz Journal: Clin Immunol Date: 2016-05-25 Impact factor: 3.969
Authors: B L Ferry; S A Misbah; P Stephens; Z Sherrell; H Lythgoe; E Bateman; C Banner; J Jones; N Groome; H M Chapel Journal: Clin Exp Immunol Date: 2004-05 Impact factor: 4.330
Authors: Aziz Bousfiha; Leïla Jeddane; Waleed Al-Herz; Fatima Ailal; Jean-Laurent Casanova; Talal Chatila; Mary Ellen Conley; Charlotte Cunningham-Rundles; Amos Etzioni; Jose Luis Franco; H Bobby Gaspar; Steven M Holland; Christoph Klein; Shigeaki Nonoyama; Hans D Ochs; Eric Oksenhendler; Capucine Picard; Jennifer M Puck; Kathleen E Sullivan; Mimi L K Tang Journal: J Clin Immunol Date: 2015-10-07 Impact factor: 8.317
Authors: Gemma E Hartley; Emily S J Edwards; Julian J Bosco; Samar Ojaimi; Robert G Stirling; Paul U Cameron; Katie Flanagan; Magdalena Plebanski; Philip Mark Hogarth; Robyn E O'Hehir; Menno C van Zelm Journal: Clin Transl Immunology Date: 2020-10-16
Authors: Kissy Guevara-Hoyer; Celia Gil; Antony R Parker; Leigh J Williams; Carmen Orte; Antonia Rodriguez de la Peña; Juliana Ochoa-Grullón; Edgard Rodriguez De Frias; Irene Serrano García; Sonia García-Gómez; M José Recio; Miguel Fernández-Arquero; Rebeca Pérez de Diego; Jose Tomas Ramos; Silvia Sánchez-Ramón Journal: Front Immunol Date: 2019-04-02 Impact factor: 7.561
Authors: J Ochoa-Grullón; C Orte; A Rodríguez de la Peña; K Guevara-Hoyer; G Cordero Torres; M Fernández-Arquero; I Serrano-García; M J Recio; R Pérez de Diego; S Sánchez-Ramón Journal: MethodsX Date: 2020-05-29
Authors: C Evans; E Bateman; R Steven; M Ponsford; A Cullinane; C Shenton; G Duthie; C Conlon; S Jolles; A P Huissoon; H J Longhurst; T Rahman; C Scott; G Wallis; S Harding; A R Parker; B L Ferry Journal: Clin Exp Immunol Date: 2018-04-01 Impact factor: 4.330